Trial Outcomes & Findings for An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma (NCT NCT02576509)

Last Updated: 2025-02-17

Results Overview

OS is defined as the time from the date of randomization to the date of death due to any cause in all randomized participants. Participants who are alive will be censored at the last known alive dates. Based on Kaplan-Meier Estimates.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

743 participants

Primary outcome timeframe

time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)

Results posted on

2025-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Nivolumab 240 mg Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Pre-Treatment Period STARTED	371	372
Pre-Treatment Period COMPLETED	367	363
Pre-Treatment Period NOT COMPLETED	4	9
Treatment Period STARTED	367	363
Treatment Period COMPLETED	0	0
Treatment Period NOT COMPLETED	367	363

Reasons for withdrawal

Reasons for withdrawal
Measure	Nivolumab 240 mg Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Pre-Treatment Period Participant request to stop therapy	0	2
Pre-Treatment Period Participant withdrew consent	1	5
Pre-Treatment Period Participant no longer meets criteria	3	2
Treatment Period Disease progression	263	244
Treatment Period Study drug toxicity	37	41
Treatment Period Death	1	1
Treatment Period Adverse event unrelated to study drug	39	41
Treatment Period Participant request to stop treatment	8	18
Treatment Period Participant withdrew consent	3	7
Treatment Period Lost to Follow-up	0	1
Treatment Period Maximum clinical benefit	1	0
Treatment Period Poor/non-compliance	1	1
Treatment Period Participant no longer meets criteria	1	0
Treatment Period Other reason	12	8
Treatment Period NOT REPORTED	1	0
Treatment Period Administrative reason by sponsor	0	1

Baseline Characteristics

An Investigational Immuno-therapy Study of Nivolumab Compared to Sorafenib as a First Treatment in Patients With Advanced Hepatocellular Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nivolumab 240 mg n=371 Participants Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg n=372 Participants Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity	Total n=743 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	185 Participants n=5 Participants	176 Participants n=7 Participants	361 Participants n=5 Participants
Age, Categorical >=65 years	186 Participants n=5 Participants	196 Participants n=7 Participants	382 Participants n=5 Participants
Age, Continuous	63.9 years STANDARD_DEVIATION 10.61 • n=5 Participants	64.5 years STANDARD_DEVIATION 10.91 • n=7 Participants	64.2 years STANDARD_DEVIATION 10.76 • n=5 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	55 Participants n=7 Participants	112 Participants n=5 Participants
Sex: Female, Male Male	314 Participants n=5 Participants	317 Participants n=7 Participants	631 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	10 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	180 Participants n=5 Participants	170 Participants n=7 Participants	350 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	186 Participants n=5 Participants	192 Participants n=7 Participants	378 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	165 Participants n=5 Participants	167 Participants n=7 Participants	332 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	199 Participants n=5 Participants	196 Participants n=7 Participants	395 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: time from the date of randomization to the date of death due to any cause, assessed up to June 2019 (approximately 41 months)

Population: all randomized participants

Outcome measures

Outcome measures
Measure	Nivolumab 240 mg n=371 Participants Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg n=372 Participants Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Overall Survival (OS)	16.39 Months Interval 13.93 to 18.37	14.69 Months Interval 11.89 to 17.22

SECONDARY outcome

Timeframe: the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first, assessed up to May 2019 (approximately 40 months)

Population: all randomized participants

ORR is defined as the proportion of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR is defined as the best response designation, as determined based on BICR-assessed tumor response according to RECIST 1.1, recorded between the date of randomization and the date of first objectively documented progression or the date of subsequent anti-cancer therapy, whichever occurs first. For participants without documented progression or subsequent anti-cancer therapy, all available response designations will contribute to the BOR determination. For a BOR of CR or PR, the initial response assessment must be confirmed by a consecutive assessment no less than 4 weeks (28 days) later. Estimate of (Nivolumab - Sorafenib) is based on CMH method of weighting, stratified by stratification factors

Outcome measures

Outcome measures
Measure	Nivolumab 240 mg n=371 Participants Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg n=372 Participants Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Objective Response Rate (ORR) Per BICR RECIST 1.1	15.4 Percentage of participants Interval 11.8 to 19.4	7.0 Percentage of participants Interval 4.6 to 10.1

SECONDARY outcome

Timeframe: time from the date of randomization to the date of the first objectively documented tumor progression or death, assessed up to May 2019 (approximately 40 months)

Population: all randomized participants

PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression as assessed by BICR according to RECIST 1.1 or death due to any cause in all randomized participants. Participants who die without a reported prior progression and without initiation of subsequent anti-cancer therapy will be considered to have progressed on the date of their death. Participants who did not progress or die will be censored on the date of their last tumor assessment. Participants who did not have baseline tumor assessment will be censored on the date they were randomized. Participants who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Participants who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last tumor assessment prior to subsequent anti-cancer therapy.

Outcome measures

Outcome measures
Measure	Nivolumab 240 mg n=371 Participants Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg n=372 Participants Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Progression-Free Survival (PFS)	3.68 Months Interval 3.06 to 3.88	3.75 Months Interval 3.71 to 4.47

SECONDARY outcome

Population: all randomized participants with a \>=1% PD-L1 expression all randomized participants with a \<1% PD-L1 expression all randomized participants without PD-L1 quantifiable

PD-L1 expression is defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per Dako PD-L1 IHC assay unless otherwise specified. This is referred as quantifiable PD-L1 expression. If the PD-L1 staining could not be quantified, it is further classifies as: Indeterminate: Tumor cell membrane staining hampered for reasons attributed to the biology of the tumor biopsy specimen and not because of improper sample preparation or handling. Not evaluable: Tumor biopsy specimen was not optimally collected or prepared (e.g. PD-L1 expression is neither quantifiable nor indeterminate). PD-L1 status is a dichotomized variable using an X% cut-off for quantifiable PD-L1 expression: * PD-L1 \> X %: ≥ X % PD-L1 expression * PD-L1 \< X %: \< X % PD-L1 expression where X% denotes the PD-L1 expression cut-off of 1%. Additional cut off values may also be explored. Confidence interval based on the Clopper and Pearson method.

Outcome measures

Outcome measures
Measure	Nivolumab 240 mg n=371 Participants Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg n=372 Participants Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Efficacy Based on PD-L1 Expression - OS and PFS >=1%, PFS	3.84 Months Interval 2.1 to 7.62	3.58 Months Interval 1.97 to 5.36
Efficacy Based on PD-L1 Expression - OS and PFS >=1%, OS	16.07 Months Interval 8.41 to 22.34	8.62 Months Interval 5.72 to 16.3
Efficacy Based on PD-L1 Expression - OS and PFS <1%, OS	16.72 Months Interval 13.93 to 18.56	15.24 Months Interval 12.58 to 18.1
Efficacy Based on PD-L1 Expression - OS and PFS <1%, PFS	3.61 Months Interval 2.43 to 3.81	3.75 Months Interval 3.71 to 5.32
Efficacy Based on PD-L1 Expression - OS and PFS without PD-L1 quantifiable, OS	16.23 Months Interval 5.82 to Upper limit cannot be estimated based on the data	22.05 Months Interval 1.77 to Upper limit cannot be estimated based on the data
Efficacy Based on PD-L1 Expression - OS and PFS without PD-L1 quantifiable, PFS	2.00 Months Interval 1.87 to Upper limit cannot be estimated based on the data	6.13 Months Interval 1.08 to 11.17

SECONDARY outcome

Population: all randomized participants with a \>=1% PD-L1 expression all randomized participants with a \<1% PD-L1 expression all randomized participants without PD-L1 quantifiable Note: odds ratio for participants without PD-L1 quantifiable cannot be estimated based on the data

Outcome measures

Outcome measures
Measure	Nivolumab 240 mg n=371 Participants Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg n=372 Participants Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Efficacy Based on PD-L1 Expression - ORR >=1%, ORR	28.2 Percentage of participants Interval 18.1 to 40.1	9.4 Percentage of participants Interval 3.5 to 19.3
Efficacy Based on PD-L1 Expression - ORR <1%, ORR	12.2 Percentage of participants Interval 8.7 to 16.5	6.7 Percentage of participants Interval 4.1 to 10.1
Efficacy Based on PD-L1 Expression - ORR without PD-L1 quantifiable, ORR	20.0 Percentage of participants Interval 0.5 to 71.6	0.0 Percentage of participants Interval 0.0 to 36.9

Adverse Events

Nivolumab 240 mg

Serious events: 216 serious events

Other events: 339 other events

Deaths: 321 deaths

Sorafenib 400 mg

Serious events: 216 serious events

Other events: 351 other events

Deaths: 335 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email:

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Nivolumab 240 mg n=367 participants at risk Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg n=363 participants at risk Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Blood and lymphatic system disorders Anaemia	2.2% 8/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	1.7% 6/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Blood and lymphatic system disorders Iron deficiency anaemia	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Blood and lymphatic system disorders Neutropenia	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Acute coronary syndrome	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Angina pectoris	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Aortic valve incompetence	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Atrial fibrillation	1.4% 5/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Cardiac arrest	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Cardiac failure	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Cardiac failure acute	0.54% 2/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Coronary artery disease	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Myocardial infarction	0.82% 3/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Pericardial effusion	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Pericarditis	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Cardiac disorders Sinus tachycardia	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Endocrine disorders Adrenal insufficiency	0.54% 2/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Endocrine disorders Hypophysitis	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Eye disorders Cataract	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Eye disorders Eyelid function disorder	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Eye disorders Glaucoma	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Eye disorders Retinal artery occlusion	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Eye disorders Retinal vascular disorder	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal distension	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain	1.9% 7/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	3.0% 11/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain lower	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain upper	0.54% 2/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	1.4% 5/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Anal fistula	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Ascites	2.5% 9/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	1.9% 7/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Colitis	1.4% 5/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Colitis ulcerative	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Diaphragmatic hernia	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	1.4% 5/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Diverticulum intestinal	0.54% 2/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Duodenitis haemorrhagic	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Dysphagia	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Gastric ulcer	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Gastric varices	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Gastritis	0.27% 1/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.00% 0/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	0.28% 1/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.

Other adverse events
Measure	Nivolumab 240 mg n=367 participants at risk Nivolumab 240 mg intravenously (IV) every 2 weeks until disease progression or unacceptable toxicity	Sorafenib 400 mg n=363 participants at risk Sorafenib 400 mg orally (PO) twice a day (BID) until disease progression or unacceptable toxicity
Blood and lymphatic system disorders Anaemia	9.5% 35/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	8.3% 30/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Endocrine disorders Hypothyroidism	7.9% 29/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	3.3% 12/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal distension	4.1% 15/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	6.1% 22/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain	18.8% 69/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	22.6% 82/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Abdominal pain upper	11.4% 42/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	13.8% 50/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Ascites	12.5% 46/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	12.1% 44/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Constipation	13.6% 50/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	14.3% 52/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	27.2% 100/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	52.6% 191/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Nausea	16.9% 62/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	19.3% 70/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Stomatitis	4.4% 16/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	6.9% 25/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	9.8% 36/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	11.0% 40/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
General disorders Asthenia	10.9% 40/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	11.8% 43/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
General disorders Fatigue	28.1% 103/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	32.2% 117/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
General disorders Oedema peripheral	11.7% 43/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	11.3% 41/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
General disorders Pyrexia	19.3% 71/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	16.0% 58/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Infections and infestations Nasopharyngitis	9.0% 33/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	6.3% 23/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Infections and infestations Upper respiratory tract infection	7.9% 29/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	4.1% 15/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations Alanine aminotransferase increased	13.9% 51/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	10.5% 38/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations Amylase increased	7.1% 26/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	3.9% 14/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations Aspartate aminotransferase increased	22.9% 84/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	16.5% 60/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations Blood alkaline phosphatase increased	5.2% 19/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	4.7% 17/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations Blood bilirubin increased	11.2% 41/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	13.2% 48/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations Lipase increased	10.4% 38/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	7.4% 27/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations Platelet count decreased	4.6% 17/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	7.7% 28/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Investigations Weight decreased	9.3% 34/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	18.7% 68/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Metabolism and nutrition disorders Decreased appetite	21.0% 77/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	37.2% 135/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Metabolism and nutrition disorders Hyperglycaemia	5.7% 21/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	2.2% 8/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Metabolism and nutrition disorders Hypoalbuminaemia	5.2% 19/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	8.5% 31/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Metabolism and nutrition disorders Hypokalaemia	3.5% 13/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	5.8% 21/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	14.7% 54/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	9.9% 36/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	10.4% 38/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	9.1% 33/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	4.4% 16/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	8.0% 29/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	5.2% 19/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	3.3% 12/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Nervous system disorders Dizziness	6.3% 23/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	3.9% 14/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Nervous system disorders Headache	6.5% 24/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	9.1% 33/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Psychiatric disorders Insomnia	8.7% 32/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	8.5% 31/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	12.3% 45/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	12.9% 47/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dysphonia	3.0% 11/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	13.5% 49/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.4% 27/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	6.3% 23/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Alopecia	1.6% 6/367 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.	19.6% 71/363 • All cause mortality was collected from randomization up to last survival follow up (approximately up to 98 months). Serious and non-serious adverse events were collected from first dose till 100 days after last dose of study therapy (up to approximately 95 months). The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.