Trial Outcomes & Findings for Ipilimumab With or Without Bevacizumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery (NCT NCT01950390)

NCT ID: NCT01950390

Last Updated: 2025-11-10

Results Overview

OS distributions will be estimated using the Kaplan-Meier method. The distribution of OS will be compared using the stratified log rank test with one-sided overall type I error rate of 0.100 (adjusting for the one interim analysis) and the hazard ratio of OS will be estimated using the stratified Cox proportional hazard model and one-sided 90% repeated confidence interval will be constructed.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 169 participants
• Primary outcome timeframe: Time from randomization to death from any cause, assessed up to 5 years
• Results posted on: 2025-11-10

Participant Flow

This study was activated on December 13, 2013, and closed to accrual on September 25, 2017, with a final accrual of 169 patients.

Participant milestones

Measure	Arm A (Ipilimumab) INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Overall Study STARTED	85	84
Overall Study Started Treatment	82	82
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	84	84

Reasons for withdrawal

Measure	Arm A (Ipilimumab) INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Overall Study Never started treatment	3	2
Overall Study Disease progression	45	52
Overall Study Adverse Event	22	16
Overall Study Death	5	3
Overall Study Withdrawal by Subject	5	1
Overall Study Alternative therapy	0	3
Overall Study Complicating disease	1	0
Overall Study On treatment	1	0
Overall Study Symptomatic deterioration	2	1
Overall Study Physician Decision	0	4
Overall Study Lack of clinical benefit	0	1
Overall Study Maintained PR and moved to observation only	0	1

Baseline Characteristics

Ipilimumab With or Without Bevacizumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery

Baseline characteristics by cohort

Measure	Arm A (Ipilimumab) n=85 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) n=84 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV	Total n=169 Participants Total of all reporting groups
Age, Continuous	65 years n=5 Participants	65 years n=20 Participants	65 years n=40 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	43 Participants n=20 Participants	71 Participants n=40 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	41 Participants n=20 Participants	98 Participants n=40 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=20 Participants	5 Participants n=40 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	80 Participants n=5 Participants	79 Participants n=20 Participants	159 Participants n=40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=20 Participants	5 Participants n=40 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=20 Participants	1 Participants n=40 Participants
Race (NIH/OMB) White	81 Participants n=5 Participants	80 Participants n=20 Participants	161 Participants n=40 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=20 Participants	0 Participants n=40 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	4 Participants n=20 Participants	6 Participants n=40 Participants

PRIMARY outcome

Timeframe: Time from randomization to death from any cause, assessed up to 5 years

Population: All enrolled patients

OS distributions will be estimated using the Kaplan-Meier method. The distribution of OS will be compared using the stratified log rank test with one-sided overall type I error rate of 0.100 (adjusting for the one interim analysis) and the hazard ratio of OS will be estimated using the stratified Cox proportional hazard model and one-sided 90% repeated confidence interval will be constructed.

Outcome measures

Measure	Arm A (Ipilimumab) n=85 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) n=84 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Overall Survival (OS)	20.4 months Interval 13.2 to 31.6	20.1 months Interval 13.3 to 27.6

SECONDARY outcome

Timeframe: Time from randomization to disease progression or death (whichever occurs first), assessed up to 5 years

Population: All enrolled patients

Evaluated based on international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: The appearance of one or more new lesions is also considered progression). Will be estimated using the Kaplan-Meier method. PFS distributions will be compared using the log-rank test.

Outcome measures

Measure	Arm A (Ipilimumab) n=85 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) n=84 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Progression-free Survival (PFS)	2.8 months Interval 2.6 to 3.1	4.4 months Interval 2.9 to 6.2

SECONDARY outcome

Timeframe: Up to 5 years

Population: All enrolled patients

Clinical Response Rate is defined as the percentage of patients whose tumors have a complete response (CR) or partial response (PR) to treatment. Defined by Response Evaluation Criteria in Solid Tumors version 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Measure	Arm A (Ipilimumab) n=85 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) n=84 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Clinical Response Rate	11.8 percentage of participants Interval 4.9 to 18.6	15.5 percentage of participants Interval 7.7 to 23.2

SECONDARY outcome

Timeframe: Up to 90 days after completion of study treatment, up to 5 years post-registration.

Population: All patients who received treatment

Treatment-related grade 3-5 worst degree AEs rate. Defined using the Common Terminology Criteria for Adverse Events version 4.0 criteria (version 5.0 effective April 1,2018).

Outcome measures

Measure	Arm A (Ipilimumab) n=82 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) n=82 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Incidence of Adverse Events (AE)	39 percentage of participants Interval 28.4 to 49.6	58 percentage of participants Interval 47.3 to 68.7

SECONDARY outcome

Timeframe: Up to 5 years

Population: Patients with reported IR responses

Assessed using the utility of irRC. Immune-Related Complete Response (irCR): Complete disappearance of all tumor lesions (target and non-target together with no new measurable/unmeasurable lesions) for at least 4 weeks from the date of documentation of complete response. Immune-Related Partial Response (irPR): The sum of the products of the two largest perpendicular diameters of all target lesions is measured and captured as the SPD baseline. At each subsequent tumor assessment, the SPD of the two largest perpendicular diameters of all target lesions and of new measurable lesions are added together to provide the Immune Response Sum of Product Diameters (irSPD). A decrease, relative to baseline of the irSPD compared to the previous SPD baseline, of 50% or greater is considered an immune Partial Response (irPR).

Outcome measures

Measure	Arm A (Ipilimumab) n=39 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) n=52 Participants INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Immune-related (ir) Responses Rate (Ir-CR+Ir-PR)	17.9 percentage of participants Interval 7.5 to 33.5	17.3 percentage of participants Interval 8.2 to 30.3

Adverse Events

Arm A (Ipilimumab)

Serious events: 32 serious events

Other events: 72 other events

Deaths: 57 deaths

Arm B (Ipilimumab and Bevacizumab)

Serious events: 48 serious events

Other events: 77 other events

Deaths: 54 deaths

Serious adverse events

Measure	Arm A (Ipilimumab) n=82 participants at risk INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) n=82 participants at risk INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Blood and lymphatic system disorders Anemia	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Cardiac disorders Atrial fibrillation	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
General disorders Fatigue	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	9.8% 8/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
General disorders Gait disturbance	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
General disorders Sudden death NOS	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Endocrine disorders Adrenal insufficiency	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Endocrine disorders Hypothyroidism	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Endocrine disorders Endocrine disorders - Other, specify	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Abdominal pain	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Colitis	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Colonic perforation	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Diarrhea	17.1% 14/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Mucositis oral	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Nausea	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Pancreatitis	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Proctitis	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Rectal fistula	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Vomiting	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Hepatobiliary disorders Cholecystitis	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Immune system disorders Autoimmune disorder	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Infections and infestations Lung infection	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Infections and infestations Sepsis	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Infections and infestations Sinusitis	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Infections and infestations Wound infection	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Infections and infestations Infections and infestations - Other, specify	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Alanine aminotransferase increased	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Aspartate aminotransferase increased	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Blood bilirubin increased	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Lipase increased	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Lymphocyte count decreased	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Platelet count decreased	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Serum amylase increased	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Investigations - Other, specify	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Anorexia	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Dehydration	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hypoglycemia	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hypokalemia	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hyponatremia	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Nervous system disorders Headache	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Nervous system disorders Peripheral motor neuropathy	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Psychiatric disorders Confusion	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Renal and urinary disorders Acute kidney injury	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Renal and urinary disorders Proteinuria	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Vascular disorders Hematoma	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Vascular disorders Hypertension	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	35.4% 29/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Vascular disorders Hypotension	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Vascular disorders Thromboembolic event	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.

Other adverse events

Measure	Arm A (Ipilimumab) n=82 participants at risk INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Beginning cycle 8, patients receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Ipilimumab: Given IV	Arm B (Ipilimumab and Bevacizumab) n=82 participants at risk INDUCTION THERAPY: Patients receive ipilimumab 3mg/kg IV over 90 minutes and bevacizumab 15mg/kg IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive bevacizumab as in Induction Therapy. Beginning cycle 8, patients also receive ipilimumab 3mg/kg IV over 90 minutes on day 1 of every 4 cycles (12 weeks) in the absence of disease progression or unacceptable toxicity. Bevacizumab: Given IV Ipilimumab: Given IV
Blood and lymphatic system disorders Anemia	12.2% 10/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	15.9% 13/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
General disorders Chills	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
General disorders Edema limbs	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	12.2% 10/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
General disorders Fatigue	56.1% 46/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	61.0% 50/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
General disorders Fever	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	9.8% 8/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
General disorders Pain	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Skin and subcutaneous tissue disorders Pruritus	41.5% 34/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	32.9% 27/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	42.7% 35/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	36.6% 30/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Endocrine disorders Adrenal insufficiency	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Endocrine disorders Hypothyroidism	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	18.3% 15/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Endocrine disorders Endocrine disorders - Other, specify	1.2% 1/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Abdominal pain	15.9% 13/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	14.6% 12/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Constipation	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Diarrhea	34.1% 28/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	40.2% 33/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Mucositis oral	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Nausea	19.5% 16/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	23.2% 19/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Gastrointestinal disorders Vomiting	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	11.0% 9/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Alanine aminotransferase increased	20.7% 17/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	25.6% 21/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Alkaline phosphatase increased	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Aspartate aminotransferase increased	28.0% 23/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	24.4% 20/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Creatinine increased	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	12.2% 10/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Lipase increased	12.2% 10/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	17.1% 14/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Platelet count decreased	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	9.8% 8/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Serum amylase increased	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	9.8% 8/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Weight loss	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	14.6% 12/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Investigations Investigations - Other, specify	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	15.9% 13/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Anorexia	18.3% 15/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	28.0% 23/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Dehydration	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	9.8% 8/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hyperglycemia	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	11.0% 9/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hyperuricemia	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hypokalemia	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Metabolism and nutrition disorders Hyponatremia	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	8.5% 7/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	11.0% 9/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	9.8% 8/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	17.1% 14/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Musculoskeletal and connective tissue disorders Myalgia	3.7% 3/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	9.8% 8/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	2.4% 2/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Nervous system disorders Dizziness	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	11.0% 9/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Nervous system disorders Headache	11.0% 9/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	25.6% 21/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.0% 9/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	9.8% 8/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	7.3% 6/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Renal and urinary disorders Chronic kidney disease	0.00% 0/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	6.1% 5/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Renal and urinary disorders Proteinuria	4.9% 4/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	30.5% 25/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.
Vascular disorders Hypertension	12.2% 10/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.	47.6% 39/82 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment, up to 5 years. All 169 enrolled in the trial were monitored for mortality. Only patients who started protocol therapy reported adverse events data. Serious adverse events are defined as grade 3 or higher treatment-related adverse events.

Additional Information

Study Statistician

ECOG-ACRIN Biostatistics Center

Phone: 617-632-3012

Email: eatrials@jimmy.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60