Trial Outcomes & Findings for Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma (NCT NCT02784171)

NCT ID: NCT02784171

Last Updated: 2024-12-10

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

520 participants

Primary outcome timeframe

PFS was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.

Results posted on

2024-12-10

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A - Cisplatin/Pemetrexed (Phase II) Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase II) Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab	Arm C - Pembrolizumab (Phase II Only) Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years Pembrolizumab	Arm A - Cisplatin/Pemetrexed (Phase III) Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase III) Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab
Overall Study STARTED	21	19	40	218	222
Overall Study COMPLETED	21	19	40	218	222
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A - Cisplatin/Pemetrexed (Phase II) n=21 Participants Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase II) n=19 Participants Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab	Arm C - Pembrolizumab (Phase II Only) n=40 Participants Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years Pembrolizumab	Arm A - Cisplatin/Pemetrexed (Phase III) n=218 Participants Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase III) n=222 Participants Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles	Total n=520 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants	61 Participants n=4 Participants	42 Participants n=21 Participants	129 Participants n=8 Participants
Age, Categorical >=65 years	16 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants	157 Participants n=4 Participants	180 Participants n=21 Participants	391 Participants n=8 Participants
Age, Continuous	68.5 years n=5 Participants	69 years n=7 Participants	69.1 years n=5 Participants	70.8 years n=4 Participants	70.8 years n=21 Participants	70.5 years n=8 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	50 Participants n=4 Participants	57 Participants n=21 Participants	116 Participants n=8 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	16 Participants n=7 Participants	36 Participants n=5 Participants	168 Participants n=4 Participants	165 Participants n=21 Participants	404 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants	172 Participants n=4 Participants	175 Participants n=21 Participants	423 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	45 Participants n=4 Participants	46 Participants n=21 Participants	93 Participants n=8 Participants
Region of Enrollment Canada	15 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants	67 participants n=4 Participants	70 participants n=21 Participants	185 participants n=8 Participants
Region of Enrollment Italy	6 participants n=5 Participants	8 participants n=7 Participants	18 participants n=5 Participants	106 participants n=4 Participants	106 participants n=21 Participants	244 participants n=8 Participants
Region of Enrollment France	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	45 participants n=4 Participants	46 participants n=21 Participants	91 participants n=8 Participants

PRIMARY outcome

Timeframe: PFS was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.

Outcome measures

Outcome measures
Measure	Arm A - Cisplatin/Pemetrexed n=21 Participants Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab n=19 Participants Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab	Arm C - Pembrolizumab (Phase II Only) n=40 Participants Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years Pembrolizumab
Phase II: Progression Free Survival Measured as Time From Randomization to First Observation of Objective Disease Relapse or Progression	6.7 months Interval 2.7 to 8.4	6.8 months Interval 3.9 to 15.0	5.26 months Interval 2.8 to 11.8

PRIMARY outcome

Timeframe: Survival was monitored continuously throughout the study and during follow-up. Patients were evaluated for each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.

Population: Intention to treat population.

Overall survival was defined as time from the day of randomization to death for patients died. For patients still alive at time of data-cutoff for analysis, it was censored at the last day the patients were known alive as the last of all dates .

Outcome measures

Outcome measures
Measure	Arm A - Cisplatin/Pemetrexed n=218 Participants Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab n=222 Participants Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab	Arm C - Pembrolizumab (Phase II Only) Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years Pembrolizumab
Phase III: Overall Survival Defined as Time From Randomization to the Date of Death From Any Cause	16.13 months Interval 13.08 to 18.17	17.28 months Interval 14.36 to 21.29	—

SECONDARY outcome

PFS was calculated for all randomized patients from the day of randomization until the first observation of disease progression (date of objective relapse or progression of Relapse/Progression Report) or death due to any cause (recorded in Date/Cause of Death Section of Death Report). The primary analysis for PFS was based on the progression evaluated in this study using mesothelioma-modified RECIST (mRECIST) conducted by blinded independent review (BICR).

Outcome measures

Outcome measures
Measure	Arm A - Cisplatin/Pemetrexed n=218 Participants Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab n=222 Participants Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab	Arm C - Pembrolizumab (Phase II Only) Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years Pembrolizumab
Phase III: Progression Free Survival Measured as Time From Randomization to First Observation of Objective Disease Relapse or Progression	7.16 months Interval 6.83 to 7.69	7.13 months Interval 6.93 to 8.12	—

SECONDARY outcome

Timeframe: Response was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.

Objective response rate was defined as the proportion of patients with best objective response being complete response (CR) or partial response (PR).

Outcome measures

Outcome measures
Measure	Arm A - Cisplatin/Pemetrexed n=218 Participants Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab n=222 Participants Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab	Arm C - Pembrolizumab (Phase II Only) Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years Pembrolizumab
Phase III: Objective Response Rate	83 Participants	138 Participants	—

Adverse Events

Arm A - Cisplatin/Pemetrexed (Phase II)

Serious events: 8 serious events

Other events: 20 other events

Deaths: 21 deaths

Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase II)

Serious events: 10 serious events

Other events: 18 other events

Deaths: 14 deaths

Arm C - Pembrolizumab (Phase II Only)

Serious events: 13 serious events

Other events: 38 other events

Deaths: 38 deaths

Arm A - Cisplatin/Pemetrexed (Phase III)

Serious events: 38 serious events

Other events: 200 other events

Deaths: 175 deaths

Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase III)

Serious events: 92 serious events

Other events: 217 other events

Deaths: 167 deaths

Serious adverse events

Serious adverse events
Measure	Arm A - Cisplatin/Pemetrexed (Phase II) n=21 participants at risk Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase II) n=19 participants at risk Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab	Arm C - Pembrolizumab (Phase II Only) n=40 participants at risk Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years Pembrolizumab	Arm A - Cisplatin/Pemetrexed (Phase III) n=218 participants at risk Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase III) n=222 participants at risk Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Social circumstances Social circumstances - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Hematoma	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Blood and lymphatic system disorders Anemia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Blood and lymphatic system disorders Bone marrow hypocellular	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Blood and lymphatic system disorders Febrile neutropenia	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 11/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Atrial fibrillation	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Atrial flutter	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Cardiac arrest	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Cardiac disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Heart failure	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Myocardial infarction	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Pericardial effusion	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Pericarditis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Supraventricular tachycardia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders Vertigo	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Endocrine disorders Adrenal insufficiency	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Blurred vision	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Uveitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Abdominal pain	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Colitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Colonic obstruction	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Diarrhea	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Dysphagia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Esophagitis	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Gastric ulcer	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Nausea	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Pancreatitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Vomiting	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Death NOS	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Edema limbs	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Fatigue	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Fever	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders General disorders and administration site conditions - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Non-cardiac chest pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Sudden death NOS	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Immune system disorders Allergic reaction	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Immune system disorders Immune system disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Catheter related infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Enterocolitis infectious	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Infections and infestations - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Lung infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.1% 9/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Sepsis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Skin infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Upper respiratory infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Urinary tract infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Fall	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations Alanine aminotransferase increased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations Alkaline phosphatase increased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations Aspartate aminotransferase increased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations Creatinine increased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations GGT increased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations Lipase increased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations Neutrophil count decreased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations Platelet count decreased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Anorexia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Dehydration	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Chest wall pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukemia secondary to oncology chemotherapy	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Dysarthria	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Headache	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Intracranial hemorrhage	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Myelitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Peripheral motor neuropathy	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Seizure	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Syncope	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Tremor	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Confusion	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Delirium	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Acute kidney injury	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Pelvic pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Chylothorax	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.6% 8/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Respiratory thoracic and mediastinal disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Hypertension	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Hypotension	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Thromboembolic event	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Vasculitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.

Other adverse events

Other adverse events
Measure	Arm A - Cisplatin/Pemetrexed (Phase II) n=21 participants at risk Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase II) n=19 participants at risk Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed Pembrolizumab	Arm C - Pembrolizumab (Phase II Only) n=40 participants at risk Pembrolizumab 200 mg\* IV 30 min Day 1 every 21 days for a total of 2 years Pembrolizumab	Arm A - Cisplatin/Pemetrexed (Phase III) n=218 participants at risk Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin Pemetrexed	Arm B - Cisplatin/Pemetrexed/Pembrolizumab (Phase III) n=222 participants at risk Pembrolizumab 200 mg\* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles
General disorders Pain	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.0% 6/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.0% 13/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.3% 14/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Hepatobiliary disorders Hepatic pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Immune system disorders Allergic reaction	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Myelitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Nervous system disorders - Other specify	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Neuralgia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Immune system disorders Immune system disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Photophobia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Uveitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Watering eyes	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.4% 14/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	13.1% 29/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Abdominal distension	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.5% 12/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	14.9% 33/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Anal mucositis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Anal pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Anal ulcer	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Bloating	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Cheilitis	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Colitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Constipation	52.4% 11/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	42.1% 8/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	35.0% 14/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	25.2% 55/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	36.9% 82/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Diarrhea	19.0% 4/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	31.6% 6/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	22.5% 9/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	13.8% 30/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	30.2% 67/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Dry mouth	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.4% 12/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Dyspepsia	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.0% 4/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.4% 14/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	8.6% 19/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Dysphagia	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.8% 6/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 11/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Esophageal pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Esophageal ulcer	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Esophagitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Fecal incontinence	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Flatulence	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Gastric hemorrhage	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Gastritis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Gastroesophageal reflux disease	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	21.1% 4/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.7% 8/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Gastrointestinal disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Gastroparesis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Gingival pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Hemorrhoids	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Mucositis oral	33.3% 7/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	36.8% 7/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	17.0% 37/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	21.2% 47/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Nausea	61.9% 13/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	68.4% 13/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	22.5% 9/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	45.4% 99/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	54.1% 120/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Oral dysesthesia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Oral pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Pancreatitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Rectal hemorrhage	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Salivary duct inflammation	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Stomach pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Toothache	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Gastrointestinal disorders Vomiting	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	36.8% 7/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	16.1% 35/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	25.7% 57/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Chills	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.6% 8/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Edema face	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Edema limbs	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.5% 5/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	8.7% 19/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	11.7% 26/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Edema trunk	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Facial pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Fatigue	81.0% 17/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	73.7% 14/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	60.0% 24/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	64.7% 141/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	68.9% 153/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Fever	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	21.1% 4/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.0% 4/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	8.3% 18/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	22.5% 50/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Flu like symptoms	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	26.3% 5/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.0% 6/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.8% 6/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.8% 15/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Gait disturbance	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders General disorders and administration site conditions - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Infusion related reaction	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.6% 8/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Infusion site extravasation	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Injection site reaction	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Irritability	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Localized edema	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Malaise	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Neck edema	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
General disorders Non-cardiac chest pain	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	31.6% 6/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	20.0% 8/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	18.3% 40/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	23.0% 51/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Bladder infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Bronchial infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Catheter related infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Conjunctivitis infective	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Enterocolitis infectious	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Eye infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Gum infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Infections and infestations - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.4% 12/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Laryngitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Lip infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Lung infection	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.7% 8/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.9% 13/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Mucosal infection	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.0% 4/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.1% 9/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Otitis externa	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Papulopustular rash	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Paronychia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Penile infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Pleural infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Rash pustular	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Sinusitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Skin infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Tooth infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Upper respiratory infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 11/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Urethral infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Urinary tract infection	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.0% 4/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.8% 15/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Vaginal infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Infections and infestations Wound infection	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Bruising	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Burn	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Fall	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.5% 10/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Fracture	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Injury poisoning and procedural complications - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Seroma	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Vascular access complication	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Injury, poisoning and procedural complications Wound dehiscence	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Investigations GGT increased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Anorexia	38.1% 8/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	31.6% 6/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	25.0% 10/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	25.2% 55/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	29.3% 65/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Dehydration	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.9% 13/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Glucose intolerance	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	17.5% 7/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.6% 28/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Back pain	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	26.3% 5/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	20.0% 8/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.8% 28/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	16.2% 36/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Bone pain	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 11/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Buttock pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Chest wall pain	19.0% 4/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	26.3% 5/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	20.0% 8/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.8% 28/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.6% 28/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Muscle weakness right-sided	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.4% 12/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.0% 4/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Musculoskeletal and connective tissue disorders Pain in extremity	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	20.0% 8/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.5% 12/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	9.9% 22/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukemia secondary to oncology chemotherapy	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign malignant and unspecified (incl cysts and polyps) - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.0% 13/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.2% 16/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Ataxia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Cognitive disturbance	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Concentration impairment	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Dizziness	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.9% 15/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.8% 24/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Dysarthria	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Dysesthesia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Dysgeusia	19.0% 4/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	13.3% 29/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.2% 27/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Extrapyramidal disorder	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Headache	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.5% 5/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.5% 12/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	9.5% 21/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Ischemia cerebrovascular	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Lethargy	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Memory impairment	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Movements involuntary	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Paresthesia	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.5% 12/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	9.5% 21/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Peripheral motor neuropathy	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Peripheral sensory neuropathy	19.0% 4/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	26.3% 5/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.0% 4/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	8.7% 19/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	14.0% 31/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Presyncope	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Seizure	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Sinus pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Somnolence	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Spasticity	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Syncope	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Nervous system disorders Tremor	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Agitation	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Anxiety	28.6% 6/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.5% 12/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.2% 16/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Confusion	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Depression	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.5% 10/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Hallucinations	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Insomnia	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	21.1% 4/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	17.5% 7/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.3% 16/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	14.4% 32/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Mania	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Psychiatric disorders Restlessness	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Acute kidney injury	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Cystitis noninfective	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Hematuria	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Renal and urinary disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Urinary frequency	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.8% 6/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.1% 9/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Urinary incontinence	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Urinary retention	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Urinary tract pain	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.9% 13/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Renal and urinary disorders Urinary urgency	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Breast pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Genital edema	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Gynecomastia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Menorrhagia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Pelvic pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Penile pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Reproductive system and breast disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Scrotal pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Vaginal dryness	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Reproductive system and breast disorders Vaginal pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.8% 6/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.4% 12/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Cough	28.6% 6/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	57.9% 11/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	32.5% 13/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	25.2% 55/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	31.5% 70/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	61.9% 13/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	57.9% 11/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	55.0% 22/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	42.7% 93/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	53.2% 118/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.9% 13/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Hiccups	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.4% 12/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Hoarseness	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Nasal congestion	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pharyngolaryngeal pain	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.0% 4/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.5% 12/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.2% 16/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.5% 10/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Postnasal drip	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.6% 8/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Productive cough	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.5% 5/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 11/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.4% 12/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Respiratory thoracic and mediastinal disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.1% 9/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Sleep apnea	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Sore throat	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Voice alteration	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Alopecia	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.8% 6/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.4% 12/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Body odor	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Bullous dermatitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Dry skin	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	17.5% 7/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.7% 17/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Erythema multiforme	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Fat atrophy	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.1% 9/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Pain of skin	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia syndrome	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Periorbital edema	9.5% 2/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Photosensitivity	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Pruritus	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.5% 5/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.5% 12/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	18.0% 40/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Rash acneiform	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.0% 4/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.4% 12/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Rash maculo-papular	19.0% 4/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	26.3% 5/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	17.5% 7/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	8.3% 18/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	16.7% 37/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.4% 14/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	12.2% 27/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Skin hypopigmentation	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Surgical and medical procedures Surgical and medical procedures - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Flushing	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Hematoma	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Hot flashes	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Hypertension	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.2% 7/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.5% 10/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Hypotension	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.1% 9/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Phlebitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Superficial thrombophlebitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Thromboembolic event	14.3% 3/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.3% 16/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	11.7% 26/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Vascular disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.3% 5/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Vascular disorders Vasculitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Heart failure	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Palpitations	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.7% 6/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Chest pain - cardiac	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Atrioventricular block first degree	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Cardiac disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Atrial fibrillation	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Atrial flutter	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.0% 2/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Paroxysmal atrial tachycardia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Sinus bradycardia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Sinus tachycardia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Cardiac disorders Supraventricular tachycardia	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders Ear and labyrinth disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders Ear pain	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders External ear inflammation	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders Hearing impaired	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.0% 13/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.5% 10/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders Middle ear inflammation	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.90% 2/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders Tinnitus	19.0% 4/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	6.4% 14/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	8.1% 18/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders Vertigo	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Ear and labyrinth disorders Vestibular disorder	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Endocrine disorders Adrenal insufficiency	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Endocrine disorders Cushingoid	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Endocrine disorders Hyperthyroidism	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.92% 2/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Endocrine disorders Hypothyroidism	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.8% 3/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	15.0% 6/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	8.6% 19/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Blurred vision	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	10.5% 2/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.5% 3/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.8% 4/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.9% 13/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Conjunctivitis	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.3% 1/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	7.8% 17/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.9% 13/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Dry eye	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	5.5% 12/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.1% 9/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Eye disorders - Other specify	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	3.7% 8/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	4.5% 10/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Eye pain	4.8% 1/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	1.4% 3/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Flashing lights	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.45% 1/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Floaters	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	2.5% 1/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.
Eye disorders Glaucoma	0.00% 0/21 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/19 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/40 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.46% 1/218 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.	0.00% 0/222 • Adverse events were monitored continuously throughout the study and during follow-up. Patients were evaluated before each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.

Additional Information

Dr. Lesley Seymour

Canadian Cancer Trials Group

Phone: 613533600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place