Trial Outcomes & Findings for Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04] (NCT NCT03734029)

NCT ID: NCT03734029

Last Updated: 2025-10-06

Results Overview

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 557 participants
• Primary outcome timeframe: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
• Results posted on: 2025-10-06

Participant Flow

A total of 557 participants were enrolled and randomized to treatment at 161 study sites in the United States (27 study sites), Japan (18 sites), France (16 sites), China (15 sites), Italy (13 sites), Spain (12 sites), Greece (8 sites), Portugal (8 sites), Republic of Korea (8 sites), Israel (6 sites), Switzerland (6 sites), Austria (4 sites), Belgium (4 sites), Russia (3 sites), Sweden (3 sites), Taiwan (3 sites), Unted Kingdom (3 sites), Canada (2 sites), and Hungary (2 sites).

All participants had been previously treated with at least 1 and no more than 2 prior lines of chemotherapy in the recurrent or metastatic setting. The treatment chosen for the Physician's Choice arm was based on the label approved in the country of drug administration. The Physician's Choice group was combined to ensure an appropriate sample size for the comparator group.

Participant milestones

Measure	Trastuzumab Deruxtecan (T-DXd) Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Overall Study STARTED	373	184
Overall Study Full Analysis Set (All Randomized Patients)	373	184
Overall Study Safety Analysis Set (All Randomized Patients Who Received at Least 1 Dose of Study Treatment)	371	172
Overall Study COMPLETED	58	3
Overall Study NOT COMPLETED	315	181

Reasons for withdrawal

Measure	Trastuzumab Deruxtecan (T-DXd) Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Overall Study Progressive disease as per RECIST v1.1	220	130
Overall Study Adverse Event	60	14
Overall Study Withdrawal by Subject	12	11
Overall Study Clinical progression by investigator	10	8
Overall Study Death	5	2
Overall Study Physician Decision	4	3
Overall Study Other	2	0
Overall Study Lost to Follow-up	0	1
Overall Study Randomized, but not treated	2	12

Baseline Characteristics

Trastuzumab Deruxtecan (DS-8201a) Versus Investigator's Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04]

Baseline characteristics by cohort

Measure	Trastuzumab Deruxtecan (T-DXd) n=373 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=184 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.	Total n=557 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
Age, Categorical Between 18 and 65 years	290 Participants n=5 Participants	136 Participants n=7 Participants	426 Participants n=5 Participants
Age, Categorical >=65 years	83 Participants n=5 Participants	48 Participants n=7 Participants	131 Participants n=5 Participants
Age, Continuous	56.5 years STANDARD_DEVIATION 10.6 • n=5 Participants	56.5 years STANDARD_DEVIATION 11.5 • n=7 Participants	56.5 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	371 Participants n=5 Participants	184 Participants n=7 Participants	555 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	176 Participants n=5 Participants	91 Participants n=7 Participants	267 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Asian	151 Participants n=5 Participants	72 Participants n=7 Participants	223 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	38 Participants n=5 Participants	17 Participants n=7 Participants	55 Participants n=5 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years

Population: Progression-free survival (PFS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=331 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=163 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer	10.1 months Interval 9.5 to 11.5	5.4 months Interval 4.4 to 7.1

SECONDARY outcome

Timeframe: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years

Population: Progression-free survival (PFS) was assessed in the Full Analysis Set.

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=373 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=184 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status	9.9 months Interval 9.0 to 11.3	5.1 months Interval 4.2 to 6.8

SECONDARY outcome

Timeframe: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years

Population: Progression-free survival (PFS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=331 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=163 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer	9.6 months Interval 8.4 to 10.0	4.2 months Interval 3.4 to 4.9

SECONDARY outcome

Timeframe: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years

Population: Progression-free survival (PFS) was assessed in the Full Analysis Set.

Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=373 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=184 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients)	8.8 months Interval 8.3 to 9.8	4.2 months Interval 3.0 to 4.5

SECONDARY outcome

Timeframe: From the date of randomization up to the date of death due to any cause, up to approximately 3 years

Population: Overall survival (OS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.

Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=331 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=163 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer	23.9 months Interval 20.8 to 24.8	17.5 months Interval 15.2 to 22.4

SECONDARY outcome

Timeframe: From the date of randomization up to the date of death due to any cause, up to approximately 3 years

Population: Overall survival events (deaths) were analyzed in the Full Analysis Set (defined as all randomized participants).

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=373 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=184 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Number of Overall Survival Events (Deaths)	149 events (deaths)	90 events (deaths)

SECONDARY outcome

Timeframe: From the date of randomization up to the date of death due to any cause, up to approximately 3 years

Population: Overall survival (OS) was assessed in the Full Analysis Set (defined as all randomized participants).

Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=373 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=184 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Overall Survival (OS) in All Patients	23.4 months Interval 20.0 to 24.8	16.8 months Interval 14.5 to 20.0

SECONDARY outcome

Timeframe: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years

Population: Best overall response and confirmed objective response rate were assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.

Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=331 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=163 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer BICR: Complete response	12 Participants	1 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer Investigator: Progressive disease	28 Participants	34 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer Investigator: Not evaluable	11 Participants	19 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer BICR: Partial response	164 Participants	26 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer BICR: Stable disease	115 Participants	81 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer BICR: Progressive disease	26 Participants	34 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer BICR: Not evaluable	14 Participants	21 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer Investigator: Complete response	5 Participants	0 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer Investigator: Partial response	163 Participants	30 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer Investigator: Stable disease	124 Participants	80 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer BICR: Confirmed Objective response rate	175 Participants	27 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer Investigator: Confirmed Objective response rate	168 Participants	30 Participants

SECONDARY outcome

Timeframe: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years

Population: Best overall response and confirmed objective response rate were assessed in the Full Analysis Set.

Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=373 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=184 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) BICR: Complete response	13 Participants	2 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) BICR: Partial response	183 Participants	28 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) BICR: Progressive disease	31 Participants	41 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) BICR: Not evaluable	17 Participants	22 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) Investigator: Complete response	6 Participants	0 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) BICR: Stable disease	129 Participants	91 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) Investigator: Partial response	187 Participants	31 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) Investigator: Stable disease	135 Participants	93 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) Investigator: Progressive disease	32 Participants	40 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) Investigator: Not evaluable	13 Participants	20 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) BICR: Confirmed Objective response rate	195 Participants	30 Participants
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) Investigator: Confirmed Objective response rate	193 Participants	31 Participants

SECONDARY outcome

Timeframe: From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years

Population: Duration of response was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.

Duration of Response (DoR) is defined as the date of the first documented objective response (complete response [CR] or partial response [PR]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=331 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=163 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer BICR: DoR	10.7 months Interval 8.5 to 13.7	6.8 months Interval 6.5 to 9.9
Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer Investigator: DoR	8.3 months Interval 7.1 to 11.1	5.6 months Interval 3.6 to 6.8

SECONDARY outcome

Timeframe: From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years

Population: Duration of response was assessed in the Full Analysis Set.

Duration of Response (DoR) is defined as the date of the first documented objective response (complete response [CR] or partial response [PR]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=373 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=184 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Duration of Response in Participants With HER2-low Breast Cancer (All Patients) BICR: DoR	10.7 months Interval 8.5 to 13.2	6.8 months Interval 6.0 to 9.9
Duration of Response in Participants With HER2-low Breast Cancer (All Patients) Investigator: DoR	8.3 months Interval 7.0 to 9.9	5.6 months Interval 3.7 to 6.6

OTHER_PRE_SPECIFIED outcome

Timeframe: From the date of randomization up to the date of death due to any cause, up to approximately 3 years

Population: All-cause mortality was assessed in the Safety Analysis Set.

All-cause mortality is defined as all anticipated and unanticipated deaths due to any cause, with the number and frequency of such events by arm or comparison group of the clinical study.

Outcome measures

Measure	Trastuzumab Deruxtecan (T-DXd) n=371 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=172 Participants Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
All-Cause Mortality	148 Participants	88 Participants

Adverse Events

Trastuzumab Deruxtecan (T-DXd)

Serious events: 103 serious events

Other events: 366 other events

Deaths: 149 deaths

Physician's Choice

Serious events: 43 serious events

Other events: 167 other events

Deaths: 90 deaths

Serious adverse events

Measure	Trastuzumab Deruxtecan (T-DXd) n=371 participants at risk Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=172 participants at risk Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Blood and lymphatic system disorders Febrile neutropenia	1.1% 4/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	2.3% 4/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Blood and lymphatic system disorders Anaemia	1.1% 4/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Blood and lymphatic system disorders Thrombocytopenia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Blood and lymphatic system disorders Neutropenia	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Cardiac disorders Cardiac failure	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Cardiac disorders Stress cardiomyopathy	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Cardiac disorders Pericardial effusion	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Ear and labyrinth disorders Meniere's disease	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Endocrine disorders Adrenal insufficiency	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Eye disorders Cataract	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Nausea	1.1% 4/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Vomiting	1.1% 4/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Constipation	0.81% 3/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Ascites	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Colitis ischaemic	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Gastrointestinal obstruction	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Pancreatitis	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Small intestinal obstruction	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Subileus	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Colitis	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Ileus	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Pyrexia	1.1% 4/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Disease progression	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Asthenia	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders General physical health deterioration	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Fatigue	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Death	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Discomfort	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Mucosal inflammation	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Non-cardiac chest pain	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Oedema peripheral	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Pain	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Malaise	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Hepatobiliary disorders Cholecystitis	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Hepatobiliary disorders Hepatic failure	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Hepatobiliary disorders Hepatic function abnormal	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Hepatobiliary disorders Hyperbilirubinaemia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Hepatobiliary disorders Jaundice	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Hepatobiliary disorders Liver injury	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Immune system disorders Contrast media allergy	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Immune system disorders Sarcoidosis	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Pneumonia	1.9% 7/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Sepsis	1.3% 5/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations COVID-19	0.81% 3/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Urinary tract infection	0.81% 3/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Urosepsis	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Appendicitis	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Cellulitis	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Cytomegalovirus infection reactivation	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Device related infection	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Empyema	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Escherichia bacteraemia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Herpes zoster	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Osteomyelitis	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Peritonitis	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Peritonitis bacterial	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Pneumocystis jirovecii pneumonia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Pyelonephritis	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Staphylococcal bacteraemia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Streptococcal bacteraemia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Upper respiratory tract infection	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Ankle fracture	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Chemical peritonitis	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Fall	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Femoral neck fracture	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Radius fracture	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Tracheal obstruction	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Overdose	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	2.9% 5/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Medication error	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.7% 3/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Neutrophil count decreased	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Platelet count decreased	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Blood bilirubin increased	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Blood creatinine increased	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Weight decreased	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Hypercalcaemia	1.1% 4/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Hyponatraemia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Cachexia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Hypokalaemia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Hypomagnesaemia	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Bone pain	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Back pain	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Pain in extremity	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Pathological fracture	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Epilepsy	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Headache	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Movement disorder	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Hypoglycaemic coma	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Psychiatric disorders Confusional state	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Renal and urinary disorders Hydronephrosis	0.54% 2/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Renal and urinary disorders Renal colic	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Renal and urinary disorders Renal failure	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Renal and urinary disorders Ureteric obstruction	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.9% 7/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.9% 7/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 5/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.81% 3/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Cough	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Pulmonary toxicity	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Social circumstances Social problem	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Vascular disorders Embolism	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Vascular disorders Hypotension	0.27% 1/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Vascular disorders Superior vena cava occlusion	0.00% 0/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.58% 1/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.

Other adverse events

Measure	Trastuzumab Deruxtecan (T-DXd) n=371 participants at risk Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes.	Physician's Choice n=172 participants at risk Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines.
Blood and lymphatic system disorders Anaemia	36.9% 137/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	25.6% 44/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Blood and lymphatic system disorders Neutropenia	13.2% 49/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	16.9% 29/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Blood and lymphatic system disorders Thrombocytopenia	6.2% 23/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	2.3% 4/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Nausea	75.7% 281/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	30.2% 52/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Vomiting	39.9% 148/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	13.4% 23/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Constipation	33.4% 124/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	22.1% 38/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Diarrhoea	27.0% 100/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	22.1% 38/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Stomatitis	11.1% 41/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	9.9% 17/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Abdominal pain	9.4% 35/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	4.7% 8/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Dyspepsia	9.2% 34/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	6.4% 11/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Abdominal pain upper	8.4% 31/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	7.6% 13/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Dry mouth	7.0% 26/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.2% 9/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.2% 23/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.7% 3/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Gastrointestinal disorders Abdominal distension	5.4% 20/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	2.9% 5/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Fatigue	29.6% 110/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	28.5% 49/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Asthenia	18.6% 69/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	14.5% 25/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Pyrexia	11.3% 42/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	12.8% 22/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Malaise	8.9% 33/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.8% 10/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
General disorders Oedema peripheral	6.5% 24/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.8% 10/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Infections and infestations Urinary tract infection	7.3% 27/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	3.5% 6/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Aspartate aminotransferase increased	24.8% 92/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	24.4% 42/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Neutrophil count decreased	21.8% 81/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	35.5% 61/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations White blood cell count decreased	21.0% 78/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	28.5% 49/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Alanine aminotransferase increased	20.2% 75/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	25.0% 43/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Platelet count decreased	19.4% 72/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	7.0% 12/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Weight decreased	15.9% 59/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	8.1% 14/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Blood alkaline phosphatase increased	9.7% 36/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	2.9% 5/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Lymphocyte count decreased	7.8% 29/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	7.0% 12/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Blood bilirubin increased	6.7% 25/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	4.1% 7/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Gamma-glutamyltransferase increased	5.4% 20/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	4.7% 8/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Investigations Blood lactate dehydrogenase increased	5.1% 19/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.2% 9/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Decreased appetite	31.8% 118/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	19.2% 33/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Hypokalaemia	10.2% 38/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	7.0% 12/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Hypoalbuminaemia	8.6% 32/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	4.7% 8/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Metabolism and nutrition disorders Hypocalcaemia	5.1% 19/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	2.9% 5/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Arthralgia	11.6% 43/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	11.6% 20/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Back pain	8.9% 33/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.8% 10/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Pain in extremity	7.8% 29/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	2.9% 5/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Musculoskeletal and connective tissue disorders Myalgia	5.9% 22/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	9.3% 16/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Headache	14.3% 53/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	6.4% 11/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Dysgeusia	10.0% 37/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	9.3% 16/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Dizziness	8.6% 32/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.2% 9/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Peripheral sensory neuropathy	4.9% 18/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	11.0% 19/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Neuropathy peripheral	3.5% 13/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	9.3% 16/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Nervous system disorders Paraesthesia	2.2% 8/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.2% 9/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Psychiatric disorders Insomnia	6.5% 24/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.2% 9/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.5% 39/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	1.2% 2/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.2% 34/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	8.1% 14/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Cough	9.4% 35/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	8.1% 14/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.7% 21/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	0.00% 0/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Skin and subcutaneous tissue disorders Alopecia	39.6% 147/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	33.1% 57/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Skin and subcutaneous tissue disorders Rash	6.5% 24/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	5.2% 9/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	1.3% 5/371 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.	14.0% 24/172 • Adverse events (AEs) were collected from the time of signing the main informed consent form up to 40 days (+7 days) after the last treatment, whether observed by the investigator or reported by the participant, up to approximately 3 years in the Safety Analysis Set. All-cause mortality was assessed in all participants who were randomized (Full Analysis Set). Please refer to the other prespecified outcome measure that also reports all-cause mortality from the Safety Analysis Set. Other AEs and SAEs were assessed in the Safety Analysis Set. The Physician's Choice (PC) treatment was based on the label approved in each country. As prespecified in the protocol for safety analysis, the PC group was combined for an appropriate sample size for the comparator group.

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo

Phone: 908-992-6400

Email: CTRinfo@dsi.com

Results disclosure agreements

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