Trial Outcomes & Findings for Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy (NCT NCT03055013)

Last Updated: 2025-12-02

Results Overview

RFS is defined as time from randomization to disease recurrence or death from any cause. Patients who did not undergo nephrectomy or were not disease-free following nephrectomy were considered as having an event at day 1. Patients that are alive without an event were censored at the date of last disease evaluation. RFS rate at 5 years was the proportion of patients who are recurrence-free and alive at 5 years based on Kaplan-Meier estimates.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

819 participants

Primary outcome timeframe

Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years

Results posted on

2025-12-02

Participant Flow

The study was activated on February 2, 2017 and closed to accrual on June 2, 2021, with a total enrollment of 819 patients.

Participant milestones

Participant milestones
Measure	Arm A (Nephrectomy + Nivolumab) Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Nephrectomy Only) Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.
Overall Study STARTED	404	415
Overall Study RCC Patients	381	399
Overall Study Patients Who Received Treatment and Were Assessed for Adverse Events	357	377
Overall Study COMPLETED	197	387
Overall Study NOT COMPLETED	207	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Nephrectomy + Nivolumab) Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Nephrectomy Only) Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.
Overall Study Adverse Event	78	0
Overall Study Death	6	0
Overall Study Disease relapse	33	0
Overall Study Withdrawal by Subject	28	0
Overall Study Other complicating disease	5	0
Overall Study Physician Decision	1	0
Overall Study Benign mass/non-RCC	4	0
Overall Study Enrolled in another trial	1	0
Overall Study Non-protocol therapy	1	0
Overall Study Incompliance	1	0
Overall Study Insurance issues	1	0
Overall Study Did not receive nivolumab and surgery	38	0
Overall Study Did not receive nivolumab	10	0
Overall Study Did not receive surgery	0	28

Baseline Characteristics

Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm B (Nephrectomy Only) n=399 Participants Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.	Total n=780 Participants Total of all reporting groups	Arm A (Nephrectomy + Nivolumab) n=381 Participants Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
Age, Continuous	61 years n=122 Participants	61 years n=243 Participants	60 years n=121 Participants
Sex: Female, Male Female	122 Participants n=122 Participants	235 Participants n=243 Participants	113 Participants n=121 Participants
Sex: Female, Male Male	277 Participants n=122 Participants	545 Participants n=243 Participants	268 Participants n=121 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	34 Participants n=122 Participants	73 Participants n=243 Participants	39 Participants n=121 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	352 Participants n=122 Participants	685 Participants n=243 Participants	333 Participants n=121 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants n=122 Participants	22 Participants n=243 Participants	9 Participants n=121 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=122 Participants	6 Participants n=243 Participants	2 Participants n=121 Participants
Race (NIH/OMB) Asian	11 Participants n=122 Participants	24 Participants n=243 Participants	13 Participants n=121 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=122 Participants	3 Participants n=243 Participants	1 Participants n=121 Participants
Race (NIH/OMB) Black or African American	29 Participants n=122 Participants	59 Participants n=243 Participants	30 Participants n=121 Participants
Race (NIH/OMB) White	326 Participants n=122 Participants	637 Participants n=243 Participants	311 Participants n=121 Participants
Race (NIH/OMB) More than one race	0 Participants n=122 Participants	0 Participants n=243 Participants	0 Participants n=121 Participants
Race (NIH/OMB) Unknown or Not Reported	27 Participants n=122 Participants	51 Participants n=243 Participants	24 Participants n=121 Participants

PRIMARY outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years

Population: All randomized RCC patients were included in this analysis.

Outcome measures

Outcome measures
Measure	Arm A (Nephrectomy + Nivolumab) n=381 Participants Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Nephrectomy Only) n=399 Participants Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.
Recurrence-free Survival (RFS) Rate at 5 Years	0.63 proportion of participants Interval 0.577 to 0.688	0.605 proportion of participants Interval 0.545 to 0.671

SECONDARY outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 1 year

Population: All randomized RCC patients who had clear cell histology according to surgery or biopsy were included in this analysis.

RFS is defined as time from randomization to disease recurrence or death from any cause. Patients who did not undergo nephrectomy or were not disease-free following nephrectomy were considered as having an event at day 1. Patients that are alive without an event were censored at the date of last disease evaluation. RFS rate at 3 years was the proportion of patients who are recurrence-free and alive at 3 years based on Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Arm A (Nephrectomy + Nivolumab) n=303 Participants Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Nephrectomy Only) n=325 Participants Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.
Recurrence-free Survival (RFS) Rate at 3 Years Among Patients With Clear Cell Histology	0.663 proportion of participants Interval 0.606 to 0.725	0.675 proportion of participants Interval 0.623 to 0.732

SECONDARY outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years

Population: All randomized patients were included in this analysis.

Overall survival is defined as time from randomization to death from any cause. Overall survival rate at 5 years was the proportion of patients who are alive at 5 years based on Kaplan-Meier estimates.

Outcome measures

Outcome measures
Measure	Arm A (Nephrectomy + Nivolumab) n=404 Participants Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Nephrectomy Only) n=415 Participants Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.
Overall Survival Rate at 5 Years	0.73 proportion of participants Interval 0.611 to 0.873	0.811 proportion of participants Interval 0.728 to 0.904

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years

Association between the primary tumor's expression of PD-L1 with outcome

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years

Association between the expression of PD-L1 on tumor tissue at nephrectomy as well as recurrence and outcome

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years

To archive images for potential central confirmation of recurrence and for future correlative work

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline, nephrectomy, 9 months and recurrence

To collect tumor and biologic specimens for future correlative studies

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years

To characterize the pharmacokinetics of nivolumab and explore exposure response relationships with respect to safety and efficacy

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years

To characterize the immunogenicity of nivolumab

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline, pre-nephrectomy, 8 weeks post-nephrectomy, 20 weeks, 40 weeks, 54 weeks, recurrence and 2 years post randomization

To evaluate differences in change from baseline in patient-reported symptoms and toxicities among patients randomized to treatment with nivolumab compared to surgery alone

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years

To explore descriptively the efficacy of treatment with nivolumab in patients with non-clear cell (including unclassified) histologies.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at 20 weeks, 40 weeks, then every 3 months for patients <2 years from randomization, then every 6 months for 3 years, then annually for 5 years

To characterize the effects of nivolumab on bone metabolism and bone density

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Nephrectomy + Nivolumab)

Serious events: 113 serious events

Other events: 278 other events

Deaths: 48 deaths

Arm B (Nephrectomy Only)

Serious events: 46 serious events

Other events: 114 other events

Deaths: 40 deaths

Serious adverse events

Other adverse events

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Arm A (Nephrectomy + Nivolumab) n=357 participants at risk Patients receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 14 days for 2 cycles. Patients then undergo partial or radical nephrectomy 7-28 days later. Patients then receive nivolumab over 30 IV on day 1. Treatment repeats every 14 days for 6 cycles, and then every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients enrolled after Amendment 4 receive nivolumab IV over 30 minutes on day 1. Patients then undergo partial or radical nephrectomy 7-28 days later. Patient then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 9 cycles in the absence of disease progression or unacceptable toxicity.	Arm B (Nephrectomy Only) n=377 participants at risk Patients undergo partial or radical nephrectomy within 8 weeks after registration followed by observation.
Skin and subcutaneous tissue disorders Rash maculo-papular	24.9% 89/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.53% 2/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Endocrine disorders Hyperthyroidism	5.0% 18/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.00% 0/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Endocrine disorders Hypothyroidism	15.1% 54/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.00% 0/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Gastrointestinal disorders Abdominal pain	8.1% 29/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	13.5% 51/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Gastrointestinal disorders Constipation	5.0% 18/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	3.4% 13/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Gastrointestinal disorders Diarrhea	12.6% 45/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.53% 2/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Gastrointestinal disorders Nausea	14.6% 52/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	6.4% 24/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Investigations Alanine aminotransferase increased	11.2% 40/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	1.1% 4/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Investigations Aspartate aminotransferase increased	11.5% 41/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.53% 2/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Investigations Creatinine increased	16.0% 57/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	8.0% 30/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Investigations Lipase increased	7.0% 25/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.53% 2/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Investigations Serum amylase increased	6.2% 22/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.27% 1/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Metabolism and nutrition disorders Anorexia	6.7% 24/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	1.3% 5/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Metabolism and nutrition disorders Hyperglycemia	5.3% 19/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	1.6% 6/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	10.1% 36/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.00% 0/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Blood and lymphatic system disorders Anemia	8.4% 30/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	5.6% 21/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
General disorders Fatigue	38.7% 138/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	7.4% 28/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
General disorders Pain	4.5% 16/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	5.6% 21/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Skin and subcutaneous tissue disorders Dry skin	5.0% 18/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.00% 0/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.
Skin and subcutaneous tissue disorders Pruritus	24.9% 89/357 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.	0.53% 2/377 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 6 years All patients registered on this study were included in the all-cause mortality analysis. Patients who received treatment and were assessed for adverse events were included in the analysis of adverse events.