Trial Outcomes & Findings for A Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy After Definitive Local Therapy in Patients With High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck (NCT NCT03452137)

Last Updated: 2024-10-09

Results Overview

EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression \[per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)\] per assessment by investigator, or death from any cause, whichever occurred first. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

406 participants

Primary outcome timeframe

Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)

Results posted on

2024-10-09

Participant Flow

Participants took part in the study across 128 investigative sites in 23 countries from 03 April 2018 to 06 March 2024.

A total of 406 participants with locally advanced squamous cell carcinoma of the head and neck (SCCHN) were randomized in 1:1 ratio to receive either atezolizumab or placebo.

Participant milestones

Participant milestones
Measure	Placebo Participants received atezolizumab matching placebo, intravenous (IV) infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab Participants received atezolizumab 1200 milligrams (mg), IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Overall Study STARTED	203	203
Overall Study Received at Least One Dose of Study Drug	203	202
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	203	203

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received atezolizumab matching placebo, intravenous (IV) infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab Participants received atezolizumab 1200 milligrams (mg), IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Overall Study Death	67	70
Overall Study Lost to Follow-up	4	2
Overall Study Physician Decision	0	1
Overall Study Study Terminated by Sponsor	120	121
Overall Study Withdrawal by Subject	12	9

Baseline Characteristics

A Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy After Definitive Local Therapy in Patients With High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=203 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=203 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Total n=406 Participants Total of all reporting groups
Age, Continuous	57.7 years STANDARD_DEVIATION 10.1 • n=99 Participants	59.4 years STANDARD_DEVIATION 8.5 • n=107 Participants	58.5 years STANDARD_DEVIATION 9.4 • n=206 Participants
Sex: Female, Male Female	29 Participants n=99 Participants	35 Participants n=107 Participants	64 Participants n=206 Participants
Sex: Female, Male Male	174 Participants n=99 Participants	168 Participants n=107 Participants	342 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=99 Participants	11 Participants n=107 Participants	24 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	181 Participants n=99 Participants	183 Participants n=107 Participants	364 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=99 Participants	9 Participants n=107 Participants	18 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	61 Participants n=99 Participants	68 Participants n=107 Participants	129 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) White	135 Participants n=99 Participants	121 Participants n=107 Participants	256 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=99 Participants	12 Participants n=107 Participants	18 Participants n=206 Participants
Human papilloma virus (HPV) Status Negative	166 Participants n=99 Participants	168 Participants n=107 Participants	334 Participants n=206 Participants
Human papilloma virus (HPV) Status Positive	37 Participants n=99 Participants	35 Participants n=107 Participants	72 Participants n=206 Participants
Type of Definitive Local Therapy Primary Surgery	78 Participants n=99 Participants	79 Participants n=107 Participants	157 Participants n=206 Participants
Type of Definitive Local Therapy No Primary Surgery	125 Participants n=99 Participants	124 Participants n=107 Participants	249 Participants n=206 Participants
Response to Definitive Local Therapy Complete Response (CR)	170 Participants n=99 Participants	170 Participants n=107 Participants	340 Participants n=206 Participants
Response to Definitive Local Therapy Partial Response (PR) or Stable Disease (SD)	33 Participants n=99 Participants	33 Participants n=107 Participants	66 Participants n=206 Participants

PRIMARY outcome

Timeframe: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)

Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=203 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Investigator-Assessed Event-Free Survival (INV-assessed EFS)	52.73 months Interval 41.43 to The upper limit of the 95% confidence interval (CI) was not estimable for INV-EFS because there was an insufficient number of events.	59.47 months Interval 46.75 to The upper limit of the 95% CI was not estimable for INV-EFS because because there was an insufficient number of events.

SECONDARY outcome

Timeframe: Randomization to death from any cause (up to 5 years, 5 months)

Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment.

OS was defined as the time from randomization to death from any cause. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=203 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Overall Survival (OS)	NA months The median and lower and upper limits of the 95% CI for OS were not estimable because there was an insufficient number of events.	NA months Interval 59.47 to The median and upper limit of the 95% CI for OS were not estimable because there was an insufficient number of events.

SECONDARY outcome

Timeframe: Randomization to the first documented disease recurrence, disease progression or death from any cause, whichever occurs first (up to 5 years)

Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment.

EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. EFS was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=203 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Independent Review Facility (IRF) Assessed EFS	52.73 months Interval 43.1 to The upper limit of the 95% CI was not estimable for IRF-EFS because there was an insufficient number of events.	59.47 months Interval 45.17 to The upper limit of the 95% CI was not estimable for IRF-EFS because there was an insufficient number of events.

SECONDARY outcome

Timeframe: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years

Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Number analyzed per timepoint are unique number of participants out of all the assessed participants who remain at risk for an EFS event at that timepoint. Different participants may have contributed data for each timepoint.

EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by IRF, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 \& 4 years.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=203 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years 1 Year	72.59 percentage of participants Interval 66.41 to 78.77	71.92 percentage of participants Interval 65.68 to 78.16
Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years 2 Year	65.85 percentage of participants Interval 59.25 to 72.46	66.31 percentage of participants Interval 59.73 to 72.89
Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years 3 Year	59.87 percentage of participants Interval 52.99 to 66.76	61.07 percentage of participants Interval 54.25 to 67.88
Percentage of Participants Event-Free for IRF-assessed EFS at 1, 2, 3, and 4 Years 4 Year	54.71 percentage of participants Interval 47.51 to 61.9	54.72 percentage of participants Interval 47.52 to 61.91

SECONDARY outcome

Timeframe: From randomization to EFS event or date last known to be alive and event-free at 1, 2, 3, and 4 years

EFS was defined as the time from randomization to the first documented disease recurrence (per unequivocal radiographic evidence of local recurrence, new second primary SCCHN lesion, or development of distant metastasis), or disease progression (per RECIST v1.1) per assessment by the investigator, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD on study (including baseline). Participants without disease recurrence, progression or death at the time of analysis were censored at the time of the last tumor assessment. Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 2, 3 \& 4 years.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=203 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years 1 Year	70.84 percentage of participants Interval 64.58 to 77.1	76.01 percentage of participants Interval 70.09 to 81.93
Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years 2 Year	63.81 percentage of participants Interval 57.17 to 70.45	67.41 percentage of participants Interval 60.9 to 73.92
Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years 3 Year	58.57 percentage of participants Interval 51.73 to 65.41	61.71 percentage of participants Interval 54.94 to 68.49
Percentage of Participants Event-Free for INV-assessed EFS at 1, 2, 3, and 4 Years 4 Year	55.51 percentage of participants Interval 48.49 to 62.52	56.82 percentage of participants Interval 49.75 to 63.88

SECONDARY outcome

Timeframe: From randomization to OS event or date last known to be alive at 2, 3, and 5 Years

Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Number analyzed per timepoint are unique number of participants out of all the assessed participants who remain at risk for an OS event at that timepoint. Different participants may have contributed data for each timepoint.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=203 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Percentage of Participants Event-Free for OS at 2, 3, and 5 Years 2 Year	79.23 percentage of participants Interval 73.64 to 84.82	82.00 percentage of participants Interval 76.68 to 87.33
Percentage of Participants Event-Free for OS at 2, 3, and 5 Years 3 Year	73.59 percentage of participants Interval 67.48 to 79.7	72.34 percentage of participants Interval 66.11 to 78.56
Percentage of Participants Event-Free for OS at 2, 3, and 5 Years 5 Year	62.00 percentage of participants Interval 53.46 to 70.55	60.93 percentage of participants Interval 48.01 to 73.86

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 2 to 16 (Cycle length = 21 days); study discontinuation visit (up to 1 year); Follow-up approximately every 3 months until disease recurrence or progression (up to approximately 4.5 years)

Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptoms (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in PF was assessed using the PF scale, where participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves, or using the toilet) was scored on a 4-point scale (1=Not at All to 4=Very Much). Scores were linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.

Outcome measures

Outcome measures
Measure	Placebo n=201 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=200 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Baseline (Cycle 1 Day 1)	82.78 score on a scale Standard Deviation 16.36	83.46 score on a scale Standard Deviation 16.79
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 2 Day 1	2.40 score on a scale Standard Deviation 11.09	-0.58 score on a scale Standard Deviation 10.54
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 3 Day 1	3.75 score on a scale Standard Deviation 12.03	-0.13 score on a scale Standard Deviation 12.62
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 4 Day 1	2.90 score on a scale Standard Deviation 13.00	0.77 score on a scale Standard Deviation 13.42
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 5 Day 1	4.69 score on a scale Standard Deviation 13.86	1.60 score on a scale Standard Deviation 12.15
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 6 Day 1	4.03 score on a scale Standard Deviation 12.76	2.18 score on a scale Standard Deviation 13.87
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 7 Day 1	4.33 score on a scale Standard Deviation 13.07	3.56 score on a scale Standard Deviation 13.68
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 8 Day 1	4.63 score on a scale Standard Deviation 13.07	3.19 score on a scale Standard Deviation 13.71
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 9 Day 1	4.62 score on a scale Standard Deviation 13.86	2.96 score on a scale Standard Deviation 14.41
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 10 Day 1	4.41 score on a scale Standard Deviation 14.30	2.12 score on a scale Standard Deviation 14.22
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 11 Day 1	3.82 score on a scale Standard Deviation 14.20	3.69 score on a scale Standard Deviation 12.43
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 12 Day 1	4.35 score on a scale Standard Deviation 15.23	3.05 score on a scale Standard Deviation 14.89
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 13 Day 1	5.62 score on a scale Standard Deviation 13.63	3.30 score on a scale Standard Deviation 15.02
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 14 Day 1	6.73 score on a scale Standard Deviation 13.67	3.20 score on a scale Standard Deviation 13.36
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 15 Day 1	6.13 score on a scale Standard Deviation 13.11	3.99 score on a scale Standard Deviation 12.92
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Cycle 16 Day 1	5.92 score on a scale Standard Deviation 14.85	4.11 score on a scale Standard Deviation 12.88
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Study Discontinuation	2.94 score on a scale Standard Deviation 16.52	2.70 score on a scale Standard Deviation 14.20
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 1	1.47 score on a scale Standard Deviation 16.36	-6.63 score on a scale Standard Deviation 24.41
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 2	-1.15 score on a scale Standard Deviation 18.10	0.19 score on a scale Standard Deviation 17.34
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 3	-0.81 score on a scale Standard Deviation 17.17	2.68 score on a scale Standard Deviation 18.75
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 4	-1.90 score on a scale Standard Deviation 18.62	-2.56 score on a scale Standard Deviation 28.57
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 5	-2.00 score on a scale Standard Deviation 26.21	-6.03 score on a scale Standard Deviation 35.58
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 6	-3.61 score on a scale Standard Deviation 18.08	-3.24 score on a scale Standard Deviation 23.84
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 7	-6.75 score on a scale Standard Deviation 21.85	1.54 score on a scale Standard Deviation 24.82
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 8	-13.08 score on a scale Standard Deviation 28.96	1.36 score on a scale Standard Deviation 33.11
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 9	2.88 score on a scale Standard Deviation 14.38	4.63 score on a scale Standard Deviation 17.36
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 10	-16.43 score on a scale Standard Deviation 32.50	3.33 score on a scale Standard Deviation 13.80
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 11	-10.00 score on a scale Standard Deviation 35.31	-16.67 score on a scale Standard Deviation 24.65
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 12	-6.67 score on a scale Standard Deviation 8.43	0.00 score on a scale Standard Deviation 14.40
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 13	-5.71 score on a scale Standard Deviation 7.13	4.44 score on a scale Standard Deviation 10.18
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 14	-17.78 score on a scale Standard Deviation 42.86	-6.67 score on a scale Standard Deviation 0
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 15	-5.00 score on a scale Standard Deviation 6.38	—
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 16	2.22 score on a scale Standard Deviation 10.18	—
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 17	-3.33 score on a scale Standard Deviation 4.71	—
Change From Baseline in Physical Function (PF) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire- Core 30 (EORTC-QLQ-C30) Score Change at Follow Up 18	13.33 score on a scale Standard Deviation 0	—

SECONDARY outcome

Population: ITT population included all randomized participants, regardless of whether they received any of the assigned treatment. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

EORTC QLQ-C30 scale consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom (fatigue, nausea and vomiting, pain), global health/quality of life (QoL), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding Global Health Status (Question 29: GHS; "How would you rate your overall health during the past week?") and QoL (Question 30: QoL; "How would you rate your overall quality of life during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized. Scores range from 0-100. A higher score indicates a better outcome.

Outcome measures

Outcome measures
Measure	Placebo n=198 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=200 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 5 Day 1	5.29 score on a scale Standard Deviation 22.80	1.19 score on a scale Standard Deviation 18.25
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 6 Day 1	4.66 score on a scale Standard Deviation 23.81	3.17 score on a scale Standard Deviation 18.01
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 7 Day 1	7.25 score on a scale Standard Deviation 21.71	4.09 score on a scale Standard Deviation 17.47
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 8 Day 1	7.58 score on a scale Standard Deviation 21.48	4.25 score on a scale Standard Deviation 19.93
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 9 Day 1	6.30 score on a scale Standard Deviation 23.20	3.00 score on a scale Standard Deviation 17.93
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 10 Day 1	7.83 score on a scale Standard Deviation 22.29	3.85 score on a scale Standard Deviation 17.12
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 11 Day 1	7.65 score on a scale Standard Deviation 21.21	2.64 score on a scale Standard Deviation 17.35
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 12 Day 1	7.47 score on a scale Standard Deviation 22.52	2.60 score on a scale Standard Deviation 17.75
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 13 Day 1	8.45 score on a scale Standard Deviation 21.37	2.94 score on a scale Standard Deviation 18.41
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 14 Day 1	6.91 score on a scale Standard Deviation 21.82	3.39 score on a scale Standard Deviation 17.04
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 15 Day 1	7.21 score on a scale Standard Deviation 21.58	5.27 score on a scale Standard Deviation 18.13
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 16 Day 1	6.30 score on a scale Standard Deviation 22.87	6.05 score on a scale Standard Deviation 17.83
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Study Discontinuation	3.86 score on a scale Standard Deviation 23.64	1.55 score on a scale Standard Deviation 18.41
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 1	1.50 score on a scale Standard Deviation 25.01	-5.83 score on a scale Standard Deviation 25.32
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 2	4.67 score on a scale Standard Deviation 21.33	-0.95 score on a scale Standard Deviation 21.73
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 3	-1.77 score on a scale Standard Deviation 18.84	2.53 score on a scale Standard Deviation 18.57
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 4	0.74 score on a scale Standard Deviation 25.32	3.87 score on a scale Standard Deviation 22.51
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 5	3.16 score on a scale Standard Deviation 23.19	4.76 score on a scale Standard Deviation 23.36
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 6	6.32 score on a scale Standard Deviation 23.11	1.85 score on a scale Standard Deviation 17.28
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 7	2.45 score on a scale Standard Deviation 23.34	-10.26 score on a scale Standard Deviation 23.11
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 8	-8.33 score on a scale Standard Deviation 32.00	2.27 score on a scale Standard Deviation 11.84
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 9	3.70 score on a scale Standard Deviation 17.24	-1.85 score on a scale Standard Deviation 12.34
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 10	-15.00 score on a scale Standard Deviation 50.14	9.38 score on a scale Standard Deviation 9.38
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 11	-4.63 score on a scale Standard Deviation 50.88	-4.17 score on a scale Standard Deviation 19.84
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 12	20.00 score on a scale Standard Deviation 40.23	-14.58 score on a scale Standard Deviation 20.83
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 13	11.11 score on a scale Standard Deviation 38.61	-2.78 score on a scale Standard Deviation 12.73
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 14	8.33 score on a scale Standard Deviation 11.79	-16.67 score on a scale Standard Deviation 0
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 15	14.58 score on a scale Standard Deviation 34.94	—
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 16	2.78 score on a scale Standard Deviation 12.73	—
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 17	-8.33 score on a scale Standard Deviation 11.79	—
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Follow Up 18	8.33 score on a scale Standard Deviation 11.79	—
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Baseline (Cycle 1 Day 1)	66.92 score on a scale Standard Deviation 21.41	67.54 score on a scale Standard Deviation 20.79
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 2 Day 1	2.99 score on a scale Standard Deviation 20.32	0.09 score on a scale Standard Deviation 18.33
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 3 Day 1	4.87 score on a scale Standard Deviation 24.02	0.49 score on a scale Standard Deviation 17.35
Change From Baseline in Health-related Quality of Life (HRQoL) as Assessed by EORTC-QLQ-C30 Score Change at Cycle 4 Day 1	6.05 score on a scale Standard Deviation 21.04	1.34 score on a scale Standard Deviation 17.33

SECONDARY outcome

Timeframe: From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months)

Population: Safety evaluable population included all randomized participants who received any amount of the study treatment.

An AE is untoward medical occurrence in participant administered a pharmaceutical product \& regardless of causal relationship with this treatment. An AE can therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=202 Participants Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Number of Participants With at Least One Adverse Event (AE)	186 Participants	192 Participants

SECONDARY outcome

Timeframe: Predose and 0.5 hours post dose on Cycle 1 Day 1; Predose on Day 1 of Cycles 2, 4, 8, and 16 (Cycle length=21 days); study discontinuation visit (up to 1 year)

Population: Pharmacokinetic (PK)-evaluable population included all participants who received at least one dose of atezolizumab and provided at least one PK sample that was evaluable. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoint. Different participants may have contributed data for each timepoint.

Outcome measures

Outcome measures
Measure	Placebo n=194 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Serum Concentration of Atezolizumab Cycle 1 Day 1: Predose	NA micrograms per milliliters (ug/mL) Geometric Coefficient of Variation NA Geometric Mean and Geometric Coefficient of Variation were not evaluable as samples were below lower limit of quantification (BLLQ).	—
Serum Concentration of Atezolizumab Cycle 1 Day 1: 0.5 hours Post-dose	447 micrograms per milliliters (ug/mL) Geometric Coefficient of Variation 27.1	—
Serum Concentration of Atezolizumab Cycle 2 Day 1: Predose	99.2 micrograms per milliliters (ug/mL) Geometric Coefficient of Variation 31.1	—
Serum Concentration of Atezolizumab Cycle 4 Day 1: Predose	186 micrograms per milliliters (ug/mL) Geometric Coefficient of Variation 64.3	—
Serum Concentration of Atezolizumab Cycle 8 Day 1: Predose	238 micrograms per milliliters (ug/mL) Geometric Coefficient of Variation 40.6	—
Serum Concentration of Atezolizumab Cycle 16 Day 1: Predose	257 micrograms per milliliters (ug/mL) Geometric Coefficient of Variation 40.3	—
Serum Concentration of Atezolizumab Study Discontinuation	178 micrograms per milliliters (ug/mL) Geometric Coefficient of Variation 141.0	—

SECONDARY outcome

Timeframe: Predose on Day 1 of Cycles 1, 2, 4, 8 and 16 (Cycle length=21 days)

Population: ADA evaluable population included all randomized participants who received at least one dose of atezolizumab and who had at least one post-baseline ADA result.

Number of participants positive for Treatment Emergent ADA is the number of post-baseline evaluable participants determined to have treatment induced ADA or treatment-enhanced ADA during the study period.

Outcome measures

Outcome measures
Measure	Placebo n=192 Participants Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Number of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab	13 Participants	—

Adverse Events

Placebo

Serious events: 32 serious events

Other events: 144 other events

Deaths: 69 deaths

Atezolizumab

Serious events: 32 serious events

Other events: 155 other events

Deaths: 70 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=203 participants at risk Participants received atezolizumab matching placebo, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.	Atezolizumab n=202 participants at risk Participants received atezolizumab 1200 mg, IV infusion on Day 1 of each 21-day cycle for 16 cycles or up to 1 year or until disease recurrence, disease progression, unacceptable toxicity, consent withdrawal, or study termination by sponsor, whichever occurred first.
Blood and lymphatic system disorders Anaemia	8.9% 18/203 • Number of events 21 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	9.4% 19/202 • Number of events 24 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Blood and lymphatic system disorders Lymphopenia	10.8% 22/203 • Number of events 36 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	4.0% 8/202 • Number of events 11 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Endocrine disorders Hyperthyroidism	0.49% 1/203 • Number of events 1 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	5.4% 11/202 • Number of events 11 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Endocrine disorders Hypothyroidism	16.7% 34/203 • Number of events 36 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	26.7% 54/202 • Number of events 59 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Gastrointestinal disorders Constipation	2.5% 5/203 • Number of events 5 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	5.9% 12/202 • Number of events 13 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Gastrointestinal disorders Diarrhoea	4.9% 10/203 • Number of events 10 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	12.9% 26/202 • Number of events 40 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Gastrointestinal disorders Dry mouth	7.9% 16/203 • Number of events 16 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	8.9% 18/202 • Number of events 21 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
General disorders Asthenia	7.9% 16/203 • Number of events 22 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	5.4% 11/202 • Number of events 20 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
General disorders Fatigue	12.8% 26/203 • Number of events 30 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	14.4% 29/202 • Number of events 32 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Investigations Alanine aminotransferase increased	2.5% 5/203 • Number of events 8 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	6.4% 13/202 • Number of events 17 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Investigations Aspartate aminotransferase increased	3.0% 6/203 • Number of events 10 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	5.9% 12/202 • Number of events 14 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Investigations Blood creatinine increased	3.4% 7/203 • Number of events 7 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	5.4% 11/202 • Number of events 16 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Investigations Weight decreased	5.4% 11/203 • Number of events 11 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	6.4% 13/202 • Number of events 15 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Metabolism and nutrition disorders Decreased appetite	7.9% 16/203 • Number of events 16 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	7.9% 16/202 • Number of events 17 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Metabolism and nutrition disorders Hypomagnesaemia	5.9% 12/203 • Number of events 17 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	3.0% 6/202 • Number of events 9 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	7.9% 16/203 • Number of events 22 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	10.9% 22/202 • Number of events 27 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Musculoskeletal and connective tissue disorders Myalgia	2.5% 5/203 • Number of events 5 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	5.9% 12/202 • Number of events 13 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Nervous system disorders Headache	5.4% 11/203 • Number of events 11 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	6.9% 14/202 • Number of events 22 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Psychiatric disorders Anxiety	2.5% 5/203 • Number of events 5 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	5.9% 12/202 • Number of events 15 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Respiratory, thoracic and mediastinal disorders Cough	5.9% 12/203 • Number of events 12 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	8.4% 17/202 • Number of events 21 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.4% 11/203 • Number of events 15 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	3.0% 6/202 • Number of events 7 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Skin and subcutaneous tissue disorders Pruritus	7.4% 15/203 • Number of events 17 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	11.4% 23/202 • Number of events 27 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.
Skin and subcutaneous tissue disorders Rash	8.4% 17/203 • Number of events 18 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.	6.4% 13/202 • Number of events 25 • For adverse events (AEs): From first dose of study drug until 90 days after the last dose of study drug (up to 1 year, 3 months); For all-cause mortality: from randomization through the end of post-treatment survival follow-up (up to 5 years, 5 months) Safety-evaluable population included all randomized participants who received any amount of the study treatment.