Trial Outcomes & Findings for Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma (NCT NCT01216683)

Last Updated: 2023-06-29

Results Overview

Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy. This analysis was conducted among 222 evaluable patients for the primary analysis. The purpose of this analysis is to compare the complete remission rate of rituximab + bendamustine vs. bortezomib + rituximab + bendamustine as induction therapy, therefore, the proportion of patients with complete remission was compared between Arm B (bortezomib + rituximab + bendamustine) and Arms A and C combined (rituximab + bendamustine).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

289 participants

Primary outcome timeframe

Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years

Results posted on

2023-06-29

Participant Flow

This study was activated on December 13, 2010, accrued its first patient on February 9, 2011, and closed on May 13, 2015, with final accrual of 289 patients

Participant milestones

Participant milestones
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. rituximab: Given IV Bendamustin: Given IV	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D. rituximab: Given IV Bendamustin: Given IV bortezomib: Given IV	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. rituximab: Given IV Bendamustin: Given IV lenalidomide: Given orally
Induction STARTED	65	99	125
Induction Received Treatment and Assessed for Toxicities	65	93	122
Induction Eligible and Treated	59	85	114
Induction Included in the Primary Analysis of Complete Remission Rate During Induction Treatment	48	85	89
Induction COMPLETED	61	80	104
Induction NOT COMPLETED	4	19	21
Continuation STARTED	59	71	94
Continuation Received Continuation Treatment	59	70	89
Continuation COMPLETED	44	56	51
Continuation NOT COMPLETED	15	15	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. rituximab: Given IV Bendamustin: Given IV	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D. rituximab: Given IV Bendamustin: Given IV bortezomib: Given IV	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity. rituximab: Given IV Bendamustin: Given IV lenalidomide: Given orally
Induction Never started treatment	0	6	3
Induction Lack of Efficacy	4	3	7
Induction Adverse Event	0	5	5
Induction Death	0	0	2
Induction Withdrawal by Subject	0	4	2
Induction Other disease	0	1	2
Continuation Lack of Efficacy	3	2	7
Continuation Adverse Event	5	3	16
Continuation Death	1	0	2
Continuation Withdrawal by Subject	4	5	9
Continuation Other diseases	0	2	1
Continuation Physician Decision	1	0	1
Continuation Non-compliance	1	0	1
Continuation Insurance change	0	1	0
Continuation Mistakenly stayed on treatment for longer than expected	0	1	0
Continuation Not reported	0	0	1
Continuation Never started treatment	0	1	5

Baseline Characteristics

Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=59 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=85 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=114 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Total n=258 Participants Total of all reporting groups
Age, Continuous	59 years n=5 Participants	60 years n=7 Participants	61 years n=5 Participants	61 years n=4 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	34 Participants n=7 Participants	56 Participants n=5 Participants	116 Participants n=4 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	51 Participants n=7 Participants	58 Participants n=5 Participants	142 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	55 Participants n=5 Participants	82 Participants n=7 Participants	107 Participants n=5 Participants	244 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) White	53 Participants n=5 Participants	78 Participants n=7 Participants	102 Participants n=5 Participants	233 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants

PRIMARY outcome

Timeframe: Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years

Population: This analysis was conducted among 222 evaluable patients for the primary analysis. The purpose of this analysis is to compare the complete remission rate of rituximab + bendamustine vs. bortezomib + rituximab + bendamustine as induction therapy, therefore, the proportion of patients with complete remission was compared between Arm B (bortezomib + rituximab + bendamustine) and Arms A and C combined (rituximab + bendamustine).

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=137 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=85 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Complete Remission (CR) Rate	0.62 proportion of participants Interval 0.53 to 0.7	0.75 proportion of participants Interval 0.65 to 0.84	—

PRIMARY outcome

Timeframe: Assessed at 1 year post-induction, approximately 1.5 years

Population: All eligible and treated patients in the continuation phase of arm A + D and arm C + F. The purpose of this analysis is to compare the 1-year post-induction disease-free survival (DFS) rate with rituximab plus lenalidomide to rituximab alone as continuation therapy following induction treatment of bendamustine+rituximab, therefore, patients with induction treatment of bendamustine + rituximab + bortezomib were not included in this analysis.

1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion. The purpose of this analysis is to compare the 1-year post-induction disease-free survival (DFS) rate with rituximab plus lenalidomide to rituximab alone as continuation therapy following induction treatment of bendamustine+rituximab, therefore, patients with induction treatment of bendamustine + rituximab + bortezomib were not included in this analysis.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=53 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=84 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
1-year Post-induction Disease-free Survival (DFS) Rate	0.85 proportion of participants Interval 0.72 to 0.93	0.67 proportion of participants Interval 0.56 to 0.77	—

SECONDARY outcome

Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry

Population: This analysis was conducted among 222 evaluable patients.

Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. 3-year progression-free survival rate is the proportion of patients who were progression-free and alive at 3 years estimated using the method of Kaplan-Meier. Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, \>=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=48 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=85 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=89 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
3-year Progression-free Survival Rate	0.77 proportion of participants Interval 0.65 to 0.9	0.82 proportion of participants Interval 0.74 to 0.91	0.76 proportion of participants Interval 0.67 to 0.85

SECONDARY outcome

Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry

Population: This analysis was conducted among 222 evaluable patients.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=48 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=85 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=89 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
5-year Overall Survival Rate	0.87 proportion of participants Interval 0.79 to 0.97	0.86 proportion of participants Interval 0.77 to 0.94	0.83 proportion of participants Interval 0.75 to 0.91

SECONDARY outcome

Timeframe: Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years

Population: This analysis was conducted among 222 evaluable patients that were enrolled before activation of addendum #8. The proportion of patients with complete remission was compared between FLIPI 0-2/unknown and FLIPI 3-5 at baseline.

Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy. This analysis was conducted among 222 evaluable patients. The proportion of patients with complete remission was compared between patients with Follicular Lymphoma International Prognostic Index (FLIPI) of 3-5 and patients with FLIPI of 0-2/unknown. The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age \> 60 years, Ann Arbor stage III-IV, hemoglobin level \< 12 gm/dL, \>4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=101 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=121 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Complete Remission (CR) Rate	0.71 proportion of participants Interval 0.61 to 0.8	0.64 proportion of participants Interval 0.54 to 0.72	—

SECONDARY outcome

Timeframe: Assessed at 1 year post-induction, approximately 1.5 years

Population: This analysis was conducted among 203 evaluable patients in the continuation treatment portion of the study. The 1-year post induction disease-free survival rate was compared between patients with FLIPI of 3-5 and patients with FLIPI of 0-2/unknown.

1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion. This analysis was conducted among 203 evaluable patients in the continuation treatment portion of the study. The 1-year post induction disease-free survival rate was compared between patients with FLIPI of 3-5 and patients with FLIPI of 0-2/unknown. The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age \> 60 years, Ann Arbor stage III-IV, hemoglobin level \< 12 gm/dL, \>4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=91 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=112 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
1-year Disease-free Survival (DFS) Rate	0.84 proportion of participants Interval 0.74 to 0.9	0.74 proportion of participants Interval 0.65 to 0.82	—

SECONDARY outcome

Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry

Population: This analysis was conducted among 222 evaluable patients that were enrolled before activation of addendum #8.

Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, \>=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis. The five FLIPI risk factors were: age \> 60 years, Ann Arbor stage III-IV, hemoglobin level \< 12 gm/dL, \>4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=101 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=121 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Progression-free Survival	6.1 years Interval 6.1 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	6.2 years Interval 4.5 to The upper limit of the 95% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.	—

SECONDARY outcome

Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry

Population: This analysis was conducted among 222 evaluable patients.

Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier. The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age \> 60 years, Ann Arbor stage III-IV, hemoglobin level \< 12 gm/dL, \>4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=101 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=121 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
5-year Overall Survival Rate	0.90 proportion of participants Interval 0.84 to 0.96	0.81 proportion of participants Interval 0.74 to 0.89	—

SECONDARY outcome

Timeframe: Assessed every 4 weeks during induction treatment and every 8 weeks during continuation treatment, up to 2 years

Population: This analysis was conducted among 250 evaluable patients with baseline CIRS data available. The proportion of patients with complete remission was compared between baseline CIRS \<10 and baseline CIRS \>=10.

Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy. This analysis was conducted among 250 evaluable patients with Cumulative Illness Rating Scale (CIRS) data available. The proportion of patients with complete remission was compared between patients with CIRS \<10 and patients with CIRS \>=10. Higher CIRS scores indicate higher severity with max score of 56 points.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=207 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=43 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Complete Remission (CR) Rate	0.70 proportion of participants Interval 0.63 to 0.76	0.70 proportion of participants Interval 0.54 to 0.83	—

SECONDARY outcome

Timeframe: Assessed at 1 year post-induction, approximately 1.5 years

Population: This analysis was conducted among 250 evaluable patients with baseline Cumulative Illness Rating Scale (CIRS) data available. The proportion of patients disease-free and alive at 1 year post induction treatment was compared between patients with CIRS \<10 and patients with CIRS \>=10.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=207 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=43 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
1-year Disease-free Survival (DFS) Rate	0.62 proportion of participants Interval 0.55 to 0.69	0.65 proportion of participants Interval 0.49 to 0.79	—

SECONDARY outcome

Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry

Population: This analysis was conducted among 250 evaluable patients with baseline Cumulative Illness Rating Scale (CIRS) data available.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=207 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=43 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
3-year Progression-free Survival Rate	0.83 proportion of participants Interval 0.77 to 0.88	0.68 proportion of participants Interval 0.54 to 0.85	—

SECONDARY outcome

Timeframe: Assessed every cycle during treatment and every 6 months between 2 and 5 years from study entry

Population: This analysis was conducted among 250 evaluable patients with baseline Cumulative Illness Rating Scale (CIRS) data available.

Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier. The 5-year overall survival rate is reported by Cumulative Illness Rating Scale (CIRS) score (\<10 vs. \>=10). Higher CIRS scores indicate higher severity with max score of 56 points.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=207 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=43 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
5-year Overall Survival Rate	0.87 proportion of participants Interval 0.83 to 0.92	0.80 proportion of participants Interval 0.69 to 0.94	—

SECONDARY outcome

Timeframe: Assessed every cycle during treatment and for 30 days after discontinuation of treatment, up to 15 years

Population: This analysis was conducted among 99 patients who received bortezomib.

Peripheral neuropathy was assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Proportion of patients with grade 3 or higher peripheral neuropathy was compared between patients with subcutaneous bortezomib and patients with intravenous bortezomib.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=17 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=82 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Proportion of Patients With Grade 3 or Higher Peripheral Neuropathy	0.06 proportion of participants Interval 0.002 to 0.29	0.12 proportion of participants Interval 0.06 to 0.21	—

SECONDARY outcome

Timeframe: Assessed at baseline

Population: All enrolled patients with baseline FACT-G total score available

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=63 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=91 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=119 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Baseline	83.9 score on a scale Standard Deviation 14.2	84.7 score on a scale Standard Deviation 15.5	86.0 score on a scale Standard Deviation 16.0

SECONDARY outcome

Timeframe: Assessed at cycle 3 or cycle 4, approximately 3 or 4 months

Population: All enrolled patients with cycle 3 or cycle 4 FACT-G total score available

The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life. FACT-G total score at cycle 3 is considered as mid-treatment score. If FACT-G total score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=55 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=74 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=107 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at Mid-treatment	85.5 score on a scale Standard Deviation 15.7	84.2 score on a scale Standard Deviation 16.4	85.2 score on a scale Standard Deviation 15.9

SECONDARY outcome

Timeframe: Assessed at cycle 6, approximately 6 months

Population: All enrolled patients with cycle 6 FACT-G total score available

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=54 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=71 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=101 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy - General (FACT-G) Total Score at End of Induction Treatment	86.0 score on a scale Standard Deviation 17.7	86.5 score on a scale Standard Deviation 13.9	84.9 score on a scale Standard Deviation 18.2

SECONDARY outcome

Timeframe: Assessed at baseline

Population: All enrolled patients with baseline FACT-Lym subscale score available

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=63 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=91 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=120 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Baseline	43.8 score on a scale Standard Deviation 8.7	44.3 score on a scale Standard Deviation 9.3	44.9 score on a scale Standard Deviation 10.6

SECONDARY outcome

Timeframe: Assessed at cycle 3 or cycle 4, approximately 3 or 4 months

Population: All enrolled patients with cycle 3 or cycle 4 FACT-Lym subscale score available

The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life. FACT-Lym subscale score at cycle 3 is considered as mid-treatment score. If FACT-Lym subscale score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=55 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=75 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=108 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at Mid-induction Treatment	47.9 score on a scale Standard Deviation 7.4	46.8 score on a scale Standard Deviation 8.7	46.5 score on a scale Standard Deviation 9.5

SECONDARY outcome

Timeframe: Assessed at cycle 6, approximately 6 months

Population: All enrolled patients with cycle 6 FACT-Lym subscale score available

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=54 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=71 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=101 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Subscale Score at End of Induction Treatment	48.9 score on a scale Standard Deviation 7.5	48.4 score on a scale Standard Deviation 8.5	47.2 score on a scale Standard Deviation 9.9

SECONDARY outcome

Timeframe: Assessed at baseline

Population: All enrolled patients with baseline FACIT-Fatigue subscale score available

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=63 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=91 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=120 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Baseline	38.6 score on a scale Standard Deviation 10.5	37.9 score on a scale Standard Deviation 11.4	38.1 score on a scale Standard Deviation 12.1

SECONDARY outcome

Timeframe: Assessed at cycle 3 or cycle 4, approximately 3 or 4 months

Population: All enrolled patients with cycle 3 or cycle 4 FACIT-Fatigue subscale score available

The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life. FACIT-Fatigue subscale score at cycle 3 is considered as mid-treatment score. If FACIT-Fatigue subscale score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=55 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=75 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=108 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at Mid-induction Treatment	39.2 score on a scale Standard Deviation 9.0	34.5 score on a scale Standard Deviation 10.9	36.3 score on a scale Standard Deviation 12.3

SECONDARY outcome

Timeframe: Assessed at cycle 6, approximately 6 months

Population: All enrolled patients with cycle 6 FACIT-Fatigue subscale score available

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=54 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=71 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=100 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Subscale Score at End of Induction Treatment	39.9 score on a scale Standard Deviation 10.1	39.1 score on a scale Standard Deviation 9.8	36.3 score on a scale Standard Deviation 12.2

SECONDARY outcome

Timeframe: Assessed at baseline

Population: All enrolled patients with baseline FACT-GOG-NTX subscale score available

The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) subscale is comprised of 11 items that assess neurotoxicity with a scale of 0-4. The FACT-GOG-NTX subscale score ranges between 0 and 44. The higher the score, the better the quality of life.

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=46 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=65 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=90 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Baseline	39.9 score on a scale Standard Deviation 4.3	38.7 score on a scale Standard Deviation 6.0	38.8 score on a scale Standard Deviation 5.5

SECONDARY outcome

Timeframe: Assessed at cycle 3, approximately 3 months

Population: All enrolled patients with cycle 3 FACT-GOG-NTX subscale score available

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=58 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=80 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=109 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at Mid-induction Treatment	40.0 score on a scale Standard Deviation 4.6	38.6 score on a scale Standard Deviation 5.1	39.1 score on a scale Standard Deviation 5.2

SECONDARY outcome

Timeframe: Assessed at end of induction treatment (cycle 6), approximately 6 months

Population: All enrolled patients with cycle 6 FACT-GOG-NTX subscale score available

Outcome measures

Outcome measures
Measure	Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab) n=52 Participants Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab) n=69 Participants Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab) n=96 Participants Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) Subscale Score at the End of Induction Treatment	39.8 score on a scale Standard Deviation 4.0	36.1 score on a scale Standard Deviation 6.5	39.0 score on a scale Standard Deviation 5.9

Adverse Events

Arm A

Serious events: 51 serious events

Other events: 64 other events

Deaths: 2 deaths

Arm B

Serious events: 78 serious events

Other events: 92 other events

Deaths: 9 deaths

Arm C

Serious events: 96 serious events

Other events: 122 other events

Deaths: 12 deaths

Arm D

Serious events: 39 serious events

Other events: 59 other events

Deaths: 6 deaths

Arm E

Serious events: 44 serious events

Other events: 70 other events

Deaths: 7 deaths

Arm F

Serious events: 77 serious events

Other events: 88 other events

Deaths: 10 deaths

Serious adverse events

Serious adverse events
Measure	Arm A n=65 participants at risk Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm B n=93 participants at risk Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm C n=122 participants at risk Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm D n=59 participants at risk Arm D (continuation after Arm A): Beginning 4 weeks after the completion of Arm A induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm E n=70 participants at risk Arm E (continuation after Arm B): Beginning 4 weeks after the completion of Arm B induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm F n=89 participants at risk Arm F (continuation after Arm C): Immediately after completing Arm C induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.1% 5/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.9% 7/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Blood and lymphatic system disorders Febrile neutropenia	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.9% 6/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.1% 9/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Blood and lymphatic system disorders Hemolysis	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Blood and lymphatic system disorders Blood and lymphatic disorders - Other	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Cardiac disorders Heart failure	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Cardiac disorders Restrictive cardiomyopathy	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Death NOS	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Fatigue	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.5% 6/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.4% 9/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Fever	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Infusion related reaction	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Injection site reaction	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Non-cardiac chest pain	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 3/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Abdominal pain	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Colitis	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Constipation	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.5% 6/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 3/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Enterocolitis	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Hemorrhoids	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Mucositis oral	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Nausea	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 4/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Vomiting	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Immune system disorders Allergic reaction	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Anorectal infection	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Bladder infection	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Lip infection	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Lung infection	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.9% 7/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Otitis media	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Peripheral nerve infection	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Phlebitis infective	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Sepsis	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 3/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Sinusitis	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Skin infection	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Tooth infection	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Upper respiratory infection	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Urinary tract infection	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Infections and infestations - Other	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Alanine aminotransferase increased	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Alkaline phosphatase increased	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations CD4 lymphocytes decreased	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Cholesterol high	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Creatinine increased	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations INR increased	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Lipase increased	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Lymphocyte count decreased	67.7% 44/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	65.6% 61/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	63.1% 77/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	55.9% 33/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	50.0% 35/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	62.9% 56/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Neutrophil count decreased	33.8% 22/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	35.5% 33/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	28.7% 35/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	20.3% 12/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	18.6% 13/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	65.2% 58/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Platelet count decreased	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.7% 9/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 7/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Weight gain	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Weight loss	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations White blood cell decreased	29.2% 19/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	34.4% 32/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	24.6% 30/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	23.7% 14/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.7% 11/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	58.4% 52/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Anorexia	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Dehydration	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hyperglycemia	4.6% 3/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hypokalemia	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 3/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hyponatremia	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hypophosphatemia	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Tumor lysis syndrome	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Dizziness	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Headache	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Peripheral motor neuropathy	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.8% 11/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Presyncope	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Stroke	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Syncope	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Psychiatric disorders Agitation	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Psychiatric disorders Anxiety	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Psychiatric disorders Confusion	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Psychiatric disorders Depression	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Renal and urinary disorders Chronic kidney disease	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Vascular disorders Flushing	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Vascular disorders Hypertension	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Vascular disorders Hypotension	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Vascular disorders Lymphedema	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Vascular disorders Thromboembolic event	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.

Other adverse events

Other adverse events
Measure	Arm A n=65 participants at risk Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm B n=93 participants at risk Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm C n=122 participants at risk Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.	Arm D n=59 participants at risk Arm D (continuation after Arm A): Beginning 4 weeks after the completion of Arm A induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.	Arm E n=70 participants at risk Arm E (continuation after Arm B): Beginning 4 weeks after the completion of Arm B induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.	Arm F n=89 participants at risk Arm F (continuation after Arm C): Immediately after completing Arm C induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
Ear and labyrinth disorders Tinnitus	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Blood and lymphatic system disorders Anemia	60.0% 39/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	63.4% 59/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	54.9% 67/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	54.2% 32/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	50.0% 35/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	60.7% 54/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Chills	4.6% 3/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	17.2% 16/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.6% 8/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.2% 10/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Edema limbs	7.7% 5/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.1% 14/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.1% 16/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.2% 6/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.0% 7/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	16.9% 15/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Fatigue	81.5% 53/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	79.6% 74/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	75.4% 92/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	64.4% 38/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	72.9% 51/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	75.3% 67/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Fever	13.8% 9/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	21.5% 20/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.2% 10/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Infusion related reaction	18.5% 12/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.5% 7/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.7% 13/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Injection site reaction	4.6% 3/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 8/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
General disorders Pain	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.4% 5/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.82% 1/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Dry skin	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.8% 10/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.3% 15/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.2% 10/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Pruritus	12.3% 8/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 8/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.8% 12/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.8% 4/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	14.6% 13/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.2% 2/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	15.4% 10/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	22.6% 21/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	19.7% 24/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.6% 8/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	24.7% 22/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Abdominal pain	7.7% 5/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.9% 12/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 7/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 4/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.0% 8/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Constipation	33.8% 22/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	48.4% 45/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	37.7% 46/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.9% 7/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.0% 7/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	30.3% 27/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Diarrhea	30.8% 20/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	47.3% 44/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	22.1% 27/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	16.9% 10/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.7% 11/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	38.2% 34/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Dry mouth	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.5% 7/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.4% 9/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.1% 9/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Dyspepsia	10.8% 7/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 8/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.7% 13/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.5% 5/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.7% 6/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Mucositis oral	9.2% 6/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.5% 7/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.6% 19/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.7% 6/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Nausea	56.9% 37/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	60.2% 56/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	60.7% 74/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	16.9% 10/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.4% 8/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	29.2% 26/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Vomiting	16.9% 11/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	26.9% 25/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	23.0% 28/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.2% 10/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Gastrointestinal disorders Gastrointestinal disorders - Other	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.5% 7/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Immune system disorders Allergic reaction	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.5% 6/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.6% 8/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Lung infection	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.1% 5/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.5% 4/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Peripheral nerve infection	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Sinusitis	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 6/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Infections and infestations Upper respiratory infection	4.6% 3/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 7/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.7% 14/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Alanine aminotransferase increased	18.5% 12/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	20.4% 19/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.7% 13/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.6% 8/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	18.6% 13/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.7% 14/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Alkaline phosphatase increased	13.8% 9/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.9% 12/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.2% 10/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 6/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.4% 11/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Aspartate aminotransferase increased	18.5% 12/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	21.5% 20/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.1% 16/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.6% 8/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	24.3% 17/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.7% 14/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Blood bilirubin increased	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.2% 3/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.8% 4/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Creatinine increased	7.7% 5/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.5% 6/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 7/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.5% 5/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 4/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.4% 11/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Lymphocyte count decreased	53.8% 35/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	59.1% 55/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	50.8% 62/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	66.1% 39/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	77.1% 54/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	73.0% 65/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Neutrophil count decreased	40.0% 26/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	49.5% 46/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	38.5% 47/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	42.4% 25/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	42.9% 30/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	68.5% 61/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Platelet count decreased	40.0% 26/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	69.9% 65/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	53.3% 65/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	30.5% 18/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	30.0% 21/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	53.9% 48/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Weight loss	15.4% 10/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	21.5% 20/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	19.7% 24/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.5% 5/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.4% 8/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations White blood cell decreased	64.6% 42/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	64.5% 60/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	63.9% 78/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	66.1% 39/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	64.3% 45/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	87.6% 78/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Investigations Investigations - Other, specify	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 4/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.1% 5/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.7% 11/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Anorexia	26.2% 17/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	36.6% 34/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	37.7% 46/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.6% 8/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 6/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	23.6% 21/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Dehydration	4.6% 3/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 8/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 7/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hyperglycemia	15.4% 10/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.1% 14/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.2% 10/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.3% 9/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	20.0% 14/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.5% 12/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hypoalbuminemia	7.7% 5/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	17.2% 16/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.7% 13/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.5% 12/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hypocalcemia	9.2% 6/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.1% 14/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.8% 12/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 4/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.2% 10/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hypokalemia	9.2% 6/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.9% 12/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.8% 12/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.8% 4/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.2% 10/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hypomagnesemia	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 4/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.1% 5/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hyponatremia	7.7% 5/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	14.0% 13/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.6% 8/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.1% 5/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.1% 9/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Metabolism and nutrition disorders Hypophosphatemia	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Arthralgia	7.7% 5/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	14.0% 13/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.6% 8/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.8% 4/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.4% 8/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.0% 8/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	10.8% 7/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 8/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.2% 10/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Myalgia	10.8% 7/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.9% 12/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 7/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.5% 5/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.0% 7/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.2% 10/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Pain in extremity	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	19.4% 18/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 7/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.9% 9/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.5% 4/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective - Other	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.6% 5/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Dizziness	9.2% 6/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	14.0% 13/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.8% 12/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.1% 9/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Dysgeusia	12.3% 8/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.1% 14/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	16.4% 20/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.1% 5/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.4% 11/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Headache	13.8% 9/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	22.6% 21/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.3% 15/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	12.4% 11/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Memory impairment	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.8% 4/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.9% 2/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.5% 4/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Peripheral motor neuropathy	3.1% 2/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.6% 8/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	2.5% 3/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.0% 7/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 3/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Nervous system disorders Peripheral sensory neuropathy	23.1% 15/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	65.6% 61/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	19.7% 24/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	25.4% 15/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	60.0% 42/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	24.7% 22/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Eye disorders Blurred vision	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.5% 6/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.7% 1/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 4/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 3/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Psychiatric disorders Insomnia	7.7% 5/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.8% 11/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.5% 14/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.8% 4/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.3% 3/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.0% 8/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.4% 1/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Respiratory, thoracic and mediastinal disorders Cough	9.2% 6/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	6.5% 6/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	9.0% 11/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	11.4% 8/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.7% 14/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	10.8% 7/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	16.1% 15/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	13.1% 16/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	8.5% 5/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.1% 5/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	15.7% 14/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.4% 2/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.7% 4/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	4.5% 4/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Renal and urinary disorders Chronic kidney disease	0.00% 0/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	5.1% 3/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Vascular disorders Hypertension	1.5% 1/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	7.5% 7/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.6% 2/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Vascular disorders Hypotension	4.6% 3/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	10.8% 10/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.3% 4/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.
Vascular disorders Phlebitis	6.2% 4/65 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	1.1% 1/93 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	3.3% 4/122 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/59 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/70 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.	0.00% 0/89 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 5 years Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs). Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality. Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.

Additional Information

Study Statistician

ECOG-ACRIN Biostatistics Center

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60