Trial Outcomes & Findings for Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery (NCT NCT01274338)

Last Updated: 2025-11-10

Results Overview

Recurrence-free survival is defined as the time from randomization to recurrence or death, whichever occurs first. The following criteria constitute the only acceptable evidence of disease recurrence. Lung and liver: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Central Nervous System: A positive brain CT or MRI scan or CSF cytology. Cutaneous, Subcutaneous and Lymph Node Recurrence: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease. Bone and Other Organs: Positive cytology or biopsy in the presence of a single new lesion or the appearance of multiple lesions consistent with metastatic disease identified on two different radiologic studies: i.e., positive nuclear bone scan or PET scan and contrast GI series or ultrasound, X-ray or CT of abdomen for abdominal disease.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

1673 participants

Primary outcome timeframe

Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years

Results posted on

2025-11-10

Participant Flow

A total of 1673 patients, including 1670 adult patients and 3 pediatric patients, were accrued between May 25, 2011 and July 26, 2016. Accrual of adult patients were completed on August 15, 2014. The study was reactivated to accrue pediatric patients on September 23, 2014.

Participant milestones

Participant milestones
Measure	Arm A (HIP) Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (HDI) Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm D (HIP; Pediatric) Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17)	Arm E (HDI; Pediatric) Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (ages 12-17)	Arm F (LIP; Pediatric) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17)
Overall Study STARTED	511	636	523	1	1	1
Overall Study Received Treatment	503	520	516	1	1	1
Overall Study Data Available for the FACT-G and FACT-BRM Analyses	110	114	97	0	0	0
Overall Study Data Available for FACIT-D Analysis	109	114	97	0	0	0
Overall Study COMPLETED	108	182	198	0	0	1
Overall Study NOT COMPLETED	403	454	325	1	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (HIP) Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (HDI) Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm D (HIP; Pediatric) Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17)	Arm E (HDI; Pediatric) Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (ages 12-17)
Overall Study Lack of Efficacy	72	108	116	0	0
Overall Study Adverse Event	272	105	180	1	0
Overall Study Death	8	1	0	0	0
Overall Study Withdrawal by Subject	27	99	17	0	0
Overall Study Did not start treatment	8	116	7	0	0
Overall Study Alternative therapy	0	1	0	0	0
Overall Study Other complicating diseases	0	3	1	0	0
Overall Study Treatment arm was suspended due to toxicity	4	0	0	0	0
Overall Study Pregnancy	0	0	1	0	0
Overall Study Reason not reported	12	21	3	0	1

Baseline Characteristics

Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm D (HIP; Pediatric) n=1 Participants Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17)	Arm A (HIP) n=511 Participants Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (HDI) n=636 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=523 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm E (HDI; Pediatric) n=1 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity. (ages 12-17)	Arm F (LIP; Pediatric) n=1 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (ages 12-17)	Total n=1673 Participants Total of all reporting groups
Age, Continuous	15 years n=28 Participants	54 years n=5 Participants	54 years n=20 Participants	54 years n=40 Participants	17 years n=46 Participants	17 years n=34 Participants	54 years n=22 Participants
Sex: Female, Male Female	1 Participants n=28 Participants	169 Participants n=5 Participants	241 Participants n=20 Participants	195 Participants n=40 Participants	1 Participants n=46 Participants	0 Participants n=34 Participants	607 Participants n=22 Participants
Sex: Female, Male Male	0 Participants n=28 Participants	342 Participants n=5 Participants	395 Participants n=20 Participants	328 Participants n=40 Participants	0 Participants n=46 Participants	1 Participants n=34 Participants	1066 Participants n=22 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=28 Participants	8 Participants n=5 Participants	20 Participants n=20 Participants	16 Participants n=40 Participants	0 Participants n=46 Participants	0 Participants n=34 Participants	44 Participants n=22 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=28 Participants	484 Participants n=5 Participants	591 Participants n=20 Participants	488 Participants n=40 Participants	1 Participants n=46 Participants	1 Participants n=34 Participants	1566 Participants n=22 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=28 Participants	19 Participants n=5 Participants	25 Participants n=20 Participants	19 Participants n=40 Participants	0 Participants n=46 Participants	0 Participants n=34 Participants	63 Participants n=22 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=28 Participants	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=46 Participants	0 Participants n=34 Participants	0 Participants n=22 Participants
Race (NIH/OMB) Asian	0 Participants n=28 Participants	6 Participants n=5 Participants	2 Participants n=20 Participants	3 Participants n=40 Participants	0 Participants n=46 Participants	0 Participants n=34 Participants	11 Participants n=22 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=28 Participants	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=46 Participants	0 Participants n=34 Participants	0 Participants n=22 Participants
Race (NIH/OMB) Black or African American	0 Participants n=28 Participants	1 Participants n=5 Participants	4 Participants n=20 Participants	0 Participants n=40 Participants	0 Participants n=46 Participants	0 Participants n=34 Participants	5 Participants n=22 Participants
Race (NIH/OMB) White	1 Participants n=28 Participants	497 Participants n=5 Participants	620 Participants n=20 Participants	510 Participants n=40 Participants	1 Participants n=46 Participants	1 Participants n=34 Participants	1630 Participants n=22 Participants
Race (NIH/OMB) More than one race	0 Participants n=28 Participants	0 Participants n=5 Participants	1 Participants n=20 Participants	2 Participants n=40 Participants	0 Participants n=46 Participants	0 Participants n=34 Participants	3 Participants n=22 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=28 Participants	7 Participants n=5 Participants	9 Participants n=20 Participants	8 Participants n=40 Participants	0 Participants n=46 Participants	0 Participants n=34 Participants	24 Participants n=22 Participants

PRIMARY outcome

Timeframe: Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years

Population: Concurrently randomized patients on Arms B and C

Outcome measures

Outcome measures
Measure	Arm B (HDI) n=528 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=523 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Recurrence-free Survival (RFS; Arm B [HDI] vs. Arm C [LIP])	2.5 years Interval 1.7 to 3.3	4.5 years Interval 2.6 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.	—

PRIMARY outcome

Timeframe: Assessed every 3 months for 2 years, then every 6 months for years 3-5

Population: Concurrently randomized patients on Arms B and C

Overall survival is defined as the time from randomization to death or date last known alive.

Outcome measures

Outcome measures
Measure	Arm B (HDI) n=528 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=523 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
5-year Overall Survival (OS) Rate (Arm B [HDI] vs. Arm C [LIP])	0.67 proportion of participants Interval 0.62 to 0.72	0.72 proportion of participants Interval 0.68 to 0.76	—

PRIMARY outcome

Timeframe: Assessed every 3 months for 2 years, then every 6 months for years 3-5 and then annually up to 8 years

Population: Concurrently randomized patients on Arms A and B

Outcome measures

Outcome measures
Measure	Arm B (HDI) n=511 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=478 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Recurrence-free Survival (RFS; Arm A [HIP] vs. Arm B [HDI])	3.9 years Interval 2.9 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.	2.4 years Interval 1.6 to 3.0	—

PRIMARY outcome

Timeframe: Assessed every 3 months for 2 years, then every 6 months for years 3-5

Population: Concurrently randomized patients on Arms A and B

Overall survival is defined as the time from randomization to death or date last known alive.

Outcome measures

Outcome measures
Measure	Arm B (HDI) n=511 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=478 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
5-year Overall Survival (OS) Rate (Arm A [HIP] vs. Arm B [HDI])	0.70 proportion of participants Interval 0.65 to 0.74	0.65 proportion of participants Interval 0.6 to 0.7	—

SECONDARY outcome

Timeframe: Assessed at baseline and 3 months

Population: Patients with baseline and 3-month FACT-G assessments were included in this analysis. Pediatric patients did not participate in the quality of life part of the study.

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. Change in FACT-G total score from baseline to 3 months was calculated as month 3 score - baseline score.

Outcome measures

Outcome measures
Measure	Arm B (HDI) n=110 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=114 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=97 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Change in FACT-G (Functional Assessment of Cancer Therapy - General) Total Score From Baseline to 3 Months	-4.9 score on a scale Standard Deviation 14.1	-12.9 score on a scale Standard Deviation 14.1	-3.4 score on a scale Standard Deviation 13.2

SECONDARY outcome

Timeframe: Assessed at baseline and 3 months

Population: Patients with baseline and 3-month FACIT-D diarrhea subscale assessments were included in this analysis. Pediatric patients did not participate in the quality of life part of the study.

The diarrhea subscale of The Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) is an 11-item questionnaire with a scale of 0-4. The FACIT-D diarrhea subscale score ranges between 0 and 44. The higher the score, the better the quality of life. Change in FACIT-D diarrhea subscale score from baseline to 3 months was calculated as month 3 score - baseline score.

Outcome measures

Outcome measures
Measure	Arm B (HDI) n=109 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=114 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=97 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Change in FACIT-D (Functional Assessment of Cancer Therapy - Diarrhea) Diarrhea Subscale Score From Baseline to 3 Months	-3.7 score on a scale Standard Deviation 6.9	-0.7 score on a scale Standard Deviation 2.7	-2.2 score on a scale Standard Deviation 5.1

SECONDARY outcome

Timeframe: Assessed at baseline and 3 months

Population: Patients with baseline and 3-month FACT-BRM assessments were included in this analysis. Pediatric patients did not participate in the quality of life part of the study.

The Functional Assessment of Cancer Therapy - Biologic Response Modifiers (FACT-BRM) is a questionnaire including FACT-G (The Functional Assessment of Cancer Therapy - General) and additional sections addressing physical and mental quality of life aspects. It is a 40-item questionnaire with a scale of 0-4. The FACT-BRM total score ranges between 0 and 160. The higher the score, the better the quality of life. Change in FACT-BRM total score from baseline to 3 months is calculated as month 3 score - baseline score.

Outcome measures

Outcome measures
Measure	Arm B (HDI) n=110 Participants Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=114 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=97 Participants Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Change in FACT-BRM (Functional Assessment of Cancer Therapy - Biologic Response Modifiers) Total Score From Baseline to 3 Months	-8.3 score on a scale Standard Deviation 19.7	-22.7 score on a scale Standard Deviation 20.4	-6.2 score on a scale Standard Deviation 18.9

Adverse Events

Arm A (HIP)

Serious events: 292 serious events

Other events: 495 other events

Deaths: 153 deaths

Arm B (HDI)

Serious events: 410 serious events

Other events: 510 other events

Deaths: 168 deaths

Arm C (LIP)

Serious events: 197 serious events

Other events: 488 other events

Deaths: 135 deaths

Arm D (HIP; Pediatric)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm E (HDI; Pediatric)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm F (LIP; Pediatric)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm A (HIP) n=503 participants at risk Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (HDI) n=520 participants at risk Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=516 participants at risk Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm D (HIP; Pediatric) n=1 participants at risk Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm E (HDI; Pediatric) n=1 participants at risk Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm F (LIP; Pediatric) n=1 participants at risk Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
Ear and labyrinth disorders Hearing impaired	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Ear and labyrinth disorders Vertigo	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Ear and labyrinth disorders Vestibular disorder	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Anemia	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.77% 4/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.97% 5/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Leukocytosis	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Blood and lymphatic disorders - Other	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Acute coronary syndrome	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Atrial fibrillation	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Cardiac arrest	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Chest pain - cardiac	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Heart failure	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Left ventricular systolic dysfunction	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Myocardial infarction	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Myocarditis	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Restrictive cardiomyopathy	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Sinus tachycardia	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Supraventricular tachycardia	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Cardiac disorders Ventricular arrhythmia	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Chills	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Death NOS	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Fatigue	5.2% 26/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	23.1% 120/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.7% 14/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Fever	1.2% 6/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.77% 4/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Flu like symptoms	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.7% 14/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Injection site reaction	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Non-cardiac chest pain	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Pain	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Pruritus	2.2% 11/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.1% 11/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Rash acneiform	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.0% 40/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.96% 5/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.5% 23/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Endocrine disorders Adrenal insufficiency	3.6% 18/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.3% 12/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Endocrine disorders Hyperthyroidism	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Endocrine disorders Hypothyroidism	0.99% 5/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Endocrine disorders Endocrine disorders - Other, specify	8.5% 43/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.9% 20/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Abdominal distension	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Abdominal pain	0.80% 4/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.78% 4/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Anal fistula	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Colitis	10.3% 52/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.8% 35/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Colonic perforation	1.2% 6/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.97% 5/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Colonic ulcer	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Constipation	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Diarrhea	14.5% 73/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.77% 4/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	10.5% 54/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Dysphagia	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Enterocolitis	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.2% 6/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Esophagitis	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastric perforation	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastric ulcer	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastritis	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Ileal perforation	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Ileus	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Intra-abdominal hemorrhage	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Mucositis oral	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Nausea	3.8% 19/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.8% 25/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.97% 5/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Oral pain	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Pancreatitis	0.99% 5/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Peritoneal necrosis	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Proctitis	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Rectal fistula	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Rectal hemorrhage	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Rectal pain	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Small intestinal obstruction	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Vomiting	2.6% 13/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.3% 12/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Gastrointestinal disorders - Other	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Immune system disorders Autoimmune disorder	3.2% 16/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.97% 5/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Immune system disorders Immune system disorders - Other, specify	0.99% 5/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Abdominal infection	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Enterocolitis infectious	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Lung infection	0.99% 5/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Meningitis	0.80% 4/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Peritoneal infection	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Sepsis	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Skin infection	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Soft tissue infection	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Urinary tract infection	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Infections and infestations Infections and infestations - Other	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Alanine aminotransferase increased	8.0% 40/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	15.0% 78/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.9% 15/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Alkaline phosphatase increased	0.80% 4/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Aspartate aminotransferase increased	6.4% 32/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	11.7% 61/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.1% 11/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Blood bilirubin increased	1.2% 6/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Cholesterol high	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations CPK increased	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.0% 31/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Creatinine increased	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Ejection fraction decreased	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Lipase increased	4.6% 23/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.77% 4/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.5% 18/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Lymphocyte count decreased	0.80% 4/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	12.5% 65/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.4% 7/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Syncope	1.2% 6/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.7% 9/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Neutrophil count decreased	0.80% 4/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	39.6% 206/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Platelet count decreased	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.77% 4/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Serum amylase increased	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.97% 5/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Weight loss	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.2% 6/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations White blood cell decreased	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	13.5% 70/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Investigations - Other, specify	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Alkalosis	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Anorexia	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.5% 13/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Dehydration	3.8% 19/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.5% 8/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.4% 7/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyperglycemia	0.99% 5/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypertriglyceridemia	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.9% 10/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyperuricemia	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypoalbuminemia	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypocalcemia	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypokalemia	1.8% 9/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.2% 6/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.78% 4/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyponatremia	3.4% 17/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.2% 6/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.9% 10/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypophosphatemia	1.4% 7/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	5.6% 29/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.4% 7/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Metabolism and nutrition - Other	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Arthralgia	0.80% 4/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.77% 4/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Arthritis	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Flank pain	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	0.99% 5/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Muscle weakness left-sided	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Myalgia	1.2% 6/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.1% 11/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Pain in extremity	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective - Other	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Cognitive disturbance	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Dizziness	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.77% 4/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Encephalopathy	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Facial nerve disorder	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Headache	3.2% 16/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.9% 15/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.3% 12/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Intracranial hemorrhage	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Peripheral motor neuropathy	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Peripheral sensory neuropathy	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.78% 4/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Nervous system disorders - Other	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Eye disorders Cataract	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Eye disorders Conjunctivitis	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Eye disorders Uveitis	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Eye disorders Eye disorders - Other, specify	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Anxiety	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.3% 7/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Confusion	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Delirium	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Depression	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.3% 17/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Insomnia	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.77% 4/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Mania	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Psychosis	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Suicide attempt	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.38% 2/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Psychiatric disorders - Other, specify	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.4% 7/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.39% 2/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.40% 2/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Respiratory thoracic mediastinal - Other	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Renal and urinary disorders Acute kidney injury	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Renal and urinary disorders Chronic kidney disease	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Renal and urinary disorders Renal calculi	0.20% 1/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Renal and urinary disorders Renal and urinary disorders - Other	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Vascular disorders Hypertension	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.7% 9/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Vascular disorders Hypotension	0.99% 5/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.2% 6/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.78% 4/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Vascular disorders Thromboembolic event	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Vascular disorders Vascular disorders - Other, specify	0.00% 0/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.19% 1/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.

Other adverse events

Other adverse events
Measure	Arm A (HIP) n=503 participants at risk Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm B (HDI) n=520 participants at risk Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm C (LIP) n=516 participants at risk Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm D (HIP; Pediatric) n=1 participants at risk Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.	Arm E (HDI; Pediatric) n=1 participants at risk Patients receive high-dose recombinant interferon alpha-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alpha-2b SC on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.	Arm F (LIP; Pediatric) n=1 participants at risk Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 12 weeks for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.
General disorders Flu like symptoms	7.8% 39/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	48.8% 254/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.6% 34/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Blood and lymphatic system disorders Anemia	17.9% 90/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	40.2% 209/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	13.4% 69/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Chills	12.1% 61/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	34.2% 178/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.6% 34/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Fatigue	65.2% 328/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	87.7% 456/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	57.8% 298/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Fever	19.5% 98/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	33.5% 174/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	10.3% 53/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Malaise	2.0% 10/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.0% 31/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.2% 6/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
General disorders Pain	1.2% 6/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.0% 31/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.1% 11/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Alopecia	2.2% 11/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	22.1% 115/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.6% 8/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Dry skin	4.6% 23/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	9.8% 51/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.3% 17/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Pruritus	44.9% 226/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	16.2% 84/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	41.7% 215/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Rash maculo-papular	55.9% 281/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	18.8% 98/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	44.4% 229/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue - Other	5.4% 27/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.7% 35/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.7% 19/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Endocrine disorders Adrenal insufficiency	12.1% 61/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	8.1% 42/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Endocrine disorders Hyperthyroidism	6.2% 31/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.3% 17/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.1% 21/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Endocrine disorders Hypothyroidism	20.5% 103/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	9.6% 50/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	10.5% 54/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Endocrine disorders Endocrine disorders - Other, specify	18.7% 94/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.3% 12/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	12.6% 65/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Abdominal pain	20.5% 103/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	7.5% 39/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	17.2% 89/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Colitis	5.8% 29/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.3% 17/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Constipation	8.7% 44/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	21.2% 110/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	7.0% 36/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Diarrhea	46.5% 234/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	33.8% 176/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	44.8% 231/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Dry mouth	4.0% 20/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	16.9% 88/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.7% 14/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Mucositis oral	3.2% 16/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.7% 35/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.4% 7/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Nausea	36.2% 182/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	69.4% 361/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	28.5% 147/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Gastrointestinal disorders Vomiting	16.5% 83/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	25.6% 133/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	10.5% 54/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Alanine aminotransferase increased	27.8% 140/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	65.8% 342/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	16.7% 86/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Alkaline phosphatase increased	10.5% 53/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	8.1% 42/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	5.0% 26/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Aspartate aminotransferase increased	24.9% 125/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	70.6% 367/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	14.0% 72/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Blood bilirubin increased	4.8% 24/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	9.2% 48/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.3% 22/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations CPK increased	0.60% 3/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	33.8% 176/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.58% 3/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Lipase increased	9.5% 48/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.7% 9/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	8.5% 44/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Lymphocyte count decreased	6.4% 32/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	32.5% 169/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	10.3% 53/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Neutrophil count decreased	2.6% 13/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	61.0% 317/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.7% 19/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Platelet count decreased	6.4% 32/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	53.5% 278/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.8% 25/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Serum amylase increased	5.2% 26/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.7% 9/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.3% 22/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Weight loss	11.3% 57/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	41.2% 214/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.8% 35/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations White blood cell decreased	2.4% 12/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	52.5% 273/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.9% 15/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Investigations Investigations - Other, specify	21.3% 107/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	18.3% 95/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	17.6% 91/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Anorexia	20.3% 102/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	55.4% 288/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	14.1% 73/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Dehydration	4.0% 20/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.5% 34/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.1% 11/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyperglycemia	5.4% 27/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	7.5% 39/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.5% 18/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypoalbuminemia	6.2% 31/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	9.8% 51/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.0% 31/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypocalcemia	5.0% 25/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	17.3% 90/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.3% 17/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypokalemia	6.4% 32/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	10.0% 52/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.1% 21/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hyponatremia	7.2% 36/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.6% 24/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.7% 24/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Metabolism and nutrition disorders Hypophosphatemia	3.4% 17/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	17.9% 93/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.5% 18/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Arthralgia	11.5% 58/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	19.6% 102/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	8.5% 44/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Back pain	1.4% 7/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	5.2% 27/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.6% 8/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.0% 20/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	6.0% 31/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	1.6% 8/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Musculoskeletal and connective tissue disorders Myalgia	6.8% 34/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	29.6% 154/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.5% 23/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Dizziness	8.9% 45/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	21.0% 109/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.8% 25/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Dysgeusia	4.2% 21/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	31.7% 165/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.1% 16/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Headache	30.2% 152/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	45.8% 238/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	23.6% 122/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Nervous system disorders Peripheral sensory neuropathy	5.4% 27/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	8.3% 43/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.8% 25/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Eye disorders Blurred vision	7.4% 37/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	5.6% 29/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.9% 15/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Anxiety	3.0% 15/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	17.9% 93/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	2.7% 14/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Depression	4.0% 20/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	30.8% 160/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.3% 17/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Psychiatric disorders Insomnia	5.6% 28/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	17.7% 92/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	4.8% 25/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Cough	5.2% 26/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	8.1% 42/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.3% 17/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.6% 28/503 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	13.3% 69/520 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	3.5% 18/516 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.	0.00% 0/1 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 20 years Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.

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