A Study of Carboplatin Plus Etoposide With or Without Atezolizumab in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC) (IMpower133)

• ClinicalTrials.gov Identifier: NCT02763579
• Recruitment Status: Completed
• First Posted: May 5, 2016
• Results First Posted: June 13, 2019
• Last Update Posted: July 28, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Small Cell Lung Carcinoma
• Interventions: Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody; Drug: Carboplatin; Drug: Etoposide; Drug: Placebo
• Enrollment: 503

Participant Flow

Recruitment Details

Participants were enrolled at 114 centers in 21 countries: United States of America, Poland, Japan, Russia, Spain, Austria, Hungary, Czech Republic, South Korea, Italy, Serbia, Australia, Greece, United Kingdom, Germany, Taiwan, France, Chile, Brazil, Mexico, and China.

Pre-assignment Details

The total study population included 503 participants. The Global population included 403 participants. An additional 100 participants enrolled during the China Extension. The total China population included 10 Chinese participants from the Global population plus 100 participants from the China extension. 10 participants were part of the Global as well as China populations. Separate analyses were performed for the Global population and the China population in the study.

Arm/Group Title	Placebo + Carboplatin + Etoposide - Global	Atezolizumab + Carboplatin + Etoposide - Global	Placebo + Carboplatin + Etoposide - China	Atezolizumab + Carboplatin + Etoposide - China
Arm/Group Description	Participants in the Global population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants in the Global population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants in the China population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants in the China population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Period Title: Global Period
Started	202	201	0	0
Completed	0	0	0	0
Not Completed	202	201	0	0
Reason Not Completed
Death	167	151	0	0
Lost to Follow-up	2	4	0	0
Physician Decision	0	2	0	0
Study Terminated By Sponsor	21	26	0	0
Withdrawal by Subject	12	18	0	0
Period Title: China Period
Started	0	0	53 [1]	57 [2]
Completed	0	0	0	0
Not Completed	0	0	53	57
Reason Not Completed
Death	0	0	46	48
Lost to Follow-up	0	0	1	1
Physician Decision	0	0	0	1
Study Terminated By Sponsor	0	0	3	4
Withdrawal by Subject	0	0	3	3
[1] n=4 Chinese participants from the Global population are included in the China population.; [2] n=6 Chinese participants from the Global population are included in the China population.

Baseline Characteristics

Arm/Group Title		Placebo + Carboplatin + Etoposide - All	Atezolizumab + Carboplatin + Etoposide - All	Total
Arm/Group Description		All participants in the Global or China population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	All participants in the Global or China population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Total of all reporting groups
Overall Number of Baseline Participants		251	252	503
Baseline Analysis Population Description		The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension. Separate analyses were performed for the Global population and the China population in the study.
Age, Continuous [1]; Mean (Standard Deviation); Unit of measure: Years
Global	Number Analyzed	202 participants	201 participants	403 participants
		63.6 (9.0)	63.8 (8.8)	63.7 (8.9)
China	Number Analyzed	53 participants	57 participants	110 participants
		60.7 (8.8)	59.7 (9.0)	60.2 (8.9)
		[1] Measure Analysis Population Description: The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension.
Sex: Female, Male [1] [2]; Measure Type: Count of Participants; Unit of measure: Participants
Global	Number Analyzed	202 participants	201 participants	403 participants
	Female	70 34.7%	72 35.8%	142 35.2%
	Male	132 65.3%	129 64.2%	261 64.8%
China	Number Analyzed	53 participants	57 participants	110 participants
	Female	12 22.6%	11 19.3%	23 20.9%
	Male	41 77.4%	46 80.7%	87 79.1%
		[1] Measure Description: As reported from Electronic Case Report Form (eCRF).; [2] Measure Analysis Population Description: The Global population included 403 participants. The China population included 100 participants enrolled during the China Extension plus 10 Chinese participants from the Global population.
Ethnicity (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global	Number Analyzed	202 participants	201 participants	403 participants
	Hispanic or Latino	8 4.0%	8 4.0%	16 4.0%
	Not Hispanic or Latino	185 91.6%	187 93.0%	372 92.3%
	Unknown or Not Reported	9 4.5%	6 3.0%	15 3.7%
China	Number Analyzed	53 participants	57 participants	110 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	53 100.0%	57 100.0%	110 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension.
Race (NIH/OMB) [1]; Measure Type: Count of Participants; Unit of measure: Participants
Global	Number Analyzed	202 participants	201 participants	403 participants
	American Indian or Alaska Native	1 0.5%	0 0.0%	1 0.2%
	Asian	36 17.8%	33 16.4%	69 17.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 1.0%	1 0.5%	3 0.7%
	White	159 78.7%	163 81.1%	322 79.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	4 2.0%	4 2.0%	8 2.0%
China	Number Analyzed	53 participants	57 participants	110 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	53 100.0%	57 100.0%	110 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	0 0.0%	0 0.0%	0 0.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
		[1] Measure Analysis Population Description: The intent-to-treat (ITT) population included 503 participants (All) with 403 in the Global population. An additional 100 participants enrolled in the China Extension. The China population included 10 Chinese participants from the Global population plus 100 participants from the China Extension.

Outcome Measures

1. Primary Outcome

Title	Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
Description	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s).
Time Frame	Baseline until PD or death, whichever occurs first (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Arm/Group Title	Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	202	201
Median (95% Confidence Interval); Unit of Measure: Months
	4.3; (4.2 to 4.5)	5.2; (4.4 to 5.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0170
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.96
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Duration of Overall Survival (OS) in the Global Population
Description	OS is defined as the time from randomization to death from any cause.
Time Frame	Baseline until death from any cause (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Arm/Group Title	Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	202	201
Median (95% Confidence Interval); Unit of Measure: Months
	10.3; (9.3 to 11.3)	12.3; (10.8 to 15.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0069
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.54 to 0.91
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
Description	Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1.
Time Frame	Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Arm/Group Title	Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	202	201
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	76.7; (70.29 to 82.38)	74.1; (67.50 to 80.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.37
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
Description	DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first.
Time Frame	First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Arm/Group Title	Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	155	149
Median (95% Confidence Interval); Unit of Measure: Months
	3.1; (2.9 to 3.9)	4.1; (3.5 to 4.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0063
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.715
	Confidence Interval	(2-Sided) 95%; 0.562 to 0.911
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	PFS Rate at 6 Months and at 1 Year in Global Population
Description	PFS rates at 6 months and at 1 year is defined as the proportion of participants who are alive without disease progression 6 months and 1 year after randomization, respectively.
Time Frame	6 months, 1 year

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Arm/Group Title	Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	202	201
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
6 Months	22.39; (16.56 to 28.22)	30.86; (24.26 to 37.45)
1 Year	5.35; (2.14 to 8.56)	12.62; (7.85 to 17.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	PFS Rate at 6 months
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0593
	Comments	[Not Specified]
	Method	Z-test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	8.47
	Confidence Interval	(2-Sided) 95%; -0.33 to 17.27
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	PFS Rate at 1 year
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0133
	Comments	[Not Specified]
	Method	Z-test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	7.27
	Confidence Interval	(2-Sided) 95%; 1.52 to 13.02
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	OS Rate at 1 Year and 2 Years in the Global Population
Description	OS rates at 1 and 2 years is defined as the proportion of participants who are alive 1 year and 2 years after randomization, respectively.
Time Frame	1 year, 2 years

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Arm/Group Title	Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	202	201
Measure Type: Number; Unit of Measure: Percentage of participants
1 Year	38.23	51.69
2 Years	NA [1]	NA [1]

[1]

Insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	OS Rate at 1 year
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0095
	Comments	[Not Specified]
	Method	Z-test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Event Free Rate
	Estimated Value	13.46
	Confidence Interval	(2-Sided) 95%; 3.29 to 23.64
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population
Description	TTD according to the EORTC QLQ-C30 and EORTC QLQ-LC13 measures were evaluated in each of the following linearly transformed symptom scores: cough, dyspnea (single item), dyspnea (multi-item subscale), chest pain, or arm/shoulder pain. The linear transformation gives each individual symptom subscale a possible score of 0 to 100. For the symptom to be considered "deteriorated," a score increase of ≥10 points above baseline must be held for at least two consecutive assessments or an initial score increase of ≥10 points is followed by death within 3 weeks from the last assessment. A ≥ 10-point change in the symptoms subscale score is perceived by participants as clinically significant.
Time Frame	Baseline until deterioration per symptom subscale (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

The ITT population was defined as all randomized participants, regardless of whether the participant received the assigned treatment.

Arm/Group Title	Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	202	201
Median (95% Confidence Interval); Unit of Measure: Month
Cough	NA [1]; (16.6 to NA)	20.3 [1]; (NA to NA)
Pain in Chest	NA [1]; (10.9 to NA)	NA [1]; (NA to NA)
Pain in Arm or Shoulder	NA [1]; (8.8 to NA)	NA [1]; (9.2 to NA)
Dyspnea	5.6; (3.6 to 8.8)	NA [1]; (5.5 to NA)

[1]

Insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	Cough
	Type of Statistical Test	Superiority
	Comments	Stratified analysis. Stratification factors: Sex (male vs female) and ECOG (0 vs 1).
Statistical Test of Hypothesis	P-Value	0.3604
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.221
	Confidence Interval	(2-Sided) 95%; 0.795 to 1.874
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	Pain in Chest
	Type of Statistical Test	Superiority
	Comments	Stratified analysis. Stratification factors: Sex (male vs female) and ECOG (0 vs 1).
Statistical Test of Hypothesis	P-Value	0.7712
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.058
	Confidence Interval	(2-Sided) 95%; 0.722 to 1.553
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	Pain in Arm or Shoulder
	Type of Statistical Test	Superiority
	Comments	Stratified analysis. Stratification factors: Sex (male vs female) and ECOG (0 vs 1).
Statistical Test of Hypothesis	P-Value	0.6922
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.077
	Confidence Interval	(2-Sided) 95%; 0.747 to 1.552
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo + Carboplatin + Etoposide, Atezolizumab + Carboplatin + Etoposide
	Comments	Dyspnea
	Type of Statistical Test	Superiority
	Comments	Stratified analysis. Stratification factors: Sex (male vs female) and ECOG (0 vs 1).
Statistical Test of Hypothesis	P-Value	0.0650
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.748
	Confidence Interval	(2-Sided) 95%; 0.549 to 1.019
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Percentage of Participants With at Least One Adverse Event in the Global Population
Description	The percentage of participants with at least one adverse event in the global population.
Time Frame	Baseline until up to 90 days after end of treatment (up to approximately 49 months)

Outcome Measure Data

Analysis Population Description

The safety population included all treated participants, defined as participants who received any amount of any component of study treatment. For the safety analyses, patrticipants who received any amount of atezolizumab were analyzed as part of the Atezo + CE arm, even if atezolizumab was given in error.

Arm/Group Title	Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	196	198
Measure Type: Number; Unit of Measure: Percentage of participants
	96.4	100.0

9. Secondary Outcome

Title	Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population
Description	The baseline prevalence and post-baseline incidence of ADAs against atezolizumab.
Time Frame	Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 23 months) and 120 days after last dose (up to approximately 23 months overall)

Outcome Measure Data

Analysis Population Description

ADA analyses were based on ADA observations from participants who had received atezolizumab treatment and were evaluated for immunogenicity.

Arm/Group Title		Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:		Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed		198
Measure Type: Number; Unit of Measure: Percentage of participants
Baseline evaluable participants	Number Analyzed	196 participants
		2.0
Post-baseline evaluable participants	Number Analyzed	188 participants
		18.6

10. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population
Description	Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day.
Time Frame	Post-dose Day 1 of Cycle 1 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample.

Arm/Group Title	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed	185
Mean (Standard Deviation); Unit of Measure: μg/mL
	389 (135)

11. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population
Description	Atezolizumab pre-dose plasma concentration (Cmin) for each respective day.
Time Frame	Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days)

Outcome Measure Data

Analysis Population Description

PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample.

Arm/Group Title		Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:		Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed		194
Mean (Standard Deviation); Unit of Measure: μg/mL
Cycle 1 Day 1	Number Analyzed	194 participants
		NA [1] (NA)
Cycle 3 Day1	Number Analyzed	174 participants
		80.6 (32.1)
Cycle 4 Day 1	Number Analyzed	156 participants
		138 (56.4)
Cycle 8 Day 1	Number Analyzed	88 participants
		186 (73.5)
Cycle 16 Day 1	Number Analyzed	22 participants
		196 (63.1)
Cycle 24 Day 1	Number Analyzed	4 participants
		221 (43.4)

[1]

Below the level of detection.

12. Secondary Outcome

Title	Plasma Concentration of Carboplatin in the Global Population
Description	Plasma concentration of carboplatin in the Global population.
Time Frame	Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

Outcome Measure Data

Analysis Population Description

PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample.

Arm/Group Title		Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:		Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed		13	13
Mean (Standard Deviation); Unit of Measure: ng/mL
Pre-Dose on Day 1 of Cycle 1	Number Analyzed	12 participants	11 participants
		NA [1] (NA)	NA [1] (NA)
Before End of Infusion on Day 1 of Cycle 1	Number Analyzed	12 participants	11 participants
		13300 (4880)	11200 (5060)
Post Infusion on Day 1 of Cycle 1	Number Analyzed	11 participants	12 participants
		7200 (1880)	6860 (1670)
Pre-Dose on Day 1 of Cycle 3	Number Analyzed	12 participants	13 participants
		144 (58.3)	126 (48.1)
Before End of Infusion on Day 1 of Cycle 3	Number Analyzed	13 participants	13 participants
		13900 (3590)	11300 (5090)
Post Infusion on Day 1 of Cycle 3	Number Analyzed	13 participants	13 participants
		7180 (1630)	6540 (2200)

[1]

Below level of detection.

13. Secondary Outcome

Title	Plasma Concentration of Etoposide in the Global Population
Description	Plasma concentration of etoposide in the Global Population.
Time Frame	Predose, before end of infusion, 1 and 4 hours after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

Outcome Measure Data

Analysis Population Description

PK analyses were based on PK observations from all participants who had received atezolizumab, carboplatin, or etoposide treatment and who provided at least one evaluable atezolizumab PK sample.

Arm/Group Title		Placebo + Carboplatin + Etoposide	Atezolizumab + Carboplatin + Etoposide
Arm/Group Description:		Participants received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.	Participants received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
Overall Number of Participants Analyzed		13	13
Mean (Standard Deviation); Unit of Measure: ng/mL
Pre-Dose on Day 1 of Cycle 1	Number Analyzed	12 participants	13 participants
		NA [1] (NA)	NA [1] (NA)
Before End of Infusion on Day 1 of Cycle 1	Number Analyzed	10 participants	10 participants
		17000 (3640)	19400 (2860)
1 Hour Post Infusion on Day 1 of Cycle 1	Number Analyzed	8 participants	12 participants
		11100 (2010)	12600 (1960)
4 Hours Post Infusion on Day 1 of Cycle 1	Number Analyzed	9 participants	9 participants
		7640 (2360)	7300 (1230)
Pre-Dose on Day 1 of Cycle 3	Number Analyzed	13 participants	13 participants
		NA [1] (NA)	NA [1] (NA)
Before End of Infusion on Day 1 of Cycle 3	Number Analyzed	11 participants	9 participants
		16600 (2180)	17700 (3600)
1 Hour Post Infusion on Day 1 of Cycle 3	Number Analyzed	10 participants	13 participants
		12400 (3740)	12200 (2810)
4 Hours Post Infusion on Day 1 of Cycle 3	Number Analyzed	10 participants	11 participants
		6740 (1230)	7960 (2090)

[1]

Below level of detection.

Adverse Events

Time Frame	From the first study drug administration to the data cutoff date: 7 July 2022 (up to 49 months).
Adverse Event Reporting Description	All-cause mortality reported for deaths that occurred during study based on ITT, which included all randomized participants. Serious & other adverse events reported based on safety population, which included participants who received any amount of any component of study treatment.
Arm/Group Title	Placebo + Carboplatin + Etoposide - Global		Atezolizumab + Carboplatin + Etoposide - Global		Placebo + Carboplatin + Etoposide - China		Atezolizumab + Carboplatin + Etoposide - China
Arm/Group Description	Participants in the Global population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.		Participants in the Global population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.		Participants in the China population received intravenous infusions of placebo in combination with carboplatin to achieve an initial target AUC of 5 mg/mL/min followed by etoposide 100 mg/m^2 on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) placebo on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.		Participants in the China population received intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min) followed by etoposide 100 milligrams per square meter (mg/m^2) on Day 1 of every 21-day cycle during the induction phase (Cycles 1-4). On Days 2 and 3 of every 21-day cycle during the induction phase (Cycles 1-4), etoposide 100 mg/m^2 was administered alone. Thereafter, participants received maintenance (Cycle 5 onward) atezolizumab 1200 mg on Day 1 of every 21-day cycle until persistent radiographic PD, symptomatic deterioration, intolerable toxicity, withdrawal of consent, death, or study termination by the Sponsor.
All-Cause Mortality
	Placebo + Carboplatin + Etoposide - Global		Atezolizumab + Carboplatin + Etoposide - Global		Placebo + Carboplatin + Etoposide - China		Atezolizumab + Carboplatin + Etoposide - China
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	11/196 (5.61%)		5/198 (2.53%)		1/52 (1.92%)		3/57 (5.26%)
Serious Adverse Events
	Placebo + Carboplatin + Etoposide - Global		Atezolizumab + Carboplatin + Etoposide - Global		Placebo + Carboplatin + Etoposide - China		Atezolizumab + Carboplatin + Etoposide - China
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/196 (35.20%)		81/198 (40.91%)		14/52 (26.92%)		22/57 (38.60%)
Blood and lymphatic system disorders
Anaemia † 1	2/196 (1.02%)	2	3/198 (1.52%)	4	1/52 (1.92%)	1	0/57 (0.00%)	0
Disseminated intravascular coagulation † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Febrile neutropenia † 1	9/196 (4.59%)	9	5/198 (2.53%)	5	2/52 (3.85%)	2	1/57 (1.75%)	1
Granulocytopenia † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	1/52 (1.92%)	1	0/57 (0.00%)	0
Leukocytosis † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Leukopenia † 1	1/196 (0.51%)	1	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Myelosuppression † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	1/52 (1.92%)	1	1/57 (1.75%)	1
Neutropenia † 1	8/196 (4.08%)	8	7/198 (3.54%)	7	1/52 (1.92%)	1	1/57 (1.75%)	1
Pancytopenia † 1	4/196 (2.04%)	4	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Thrombocytopenia † 1	4/196 (2.04%)	4	5/198 (2.53%)	5	2/52 (3.85%)	2	0/57 (0.00%)	0
Cardiac disorders
Atrial fibrillation † 1	3/196 (1.53%)	4	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Atrioventricular block complete † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Cardiac failure † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Cardiac tamponade † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Cardiopulmonary failure † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Coronary artery disease † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Palpitations † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	1/52 (1.92%)	1	0/57 (0.00%)	0
Pericardial effusion † 1	1/196 (0.51%)	1	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Supraventricular tachycardia † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Endocrine disorders
Autoimmune thyroiditis † 1	0/196 (0.00%)	0	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Inappropriate antidiuretic hormone secretion † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Gastrointestinal disorders
Abdominal adhesions † 1	0/196 (0.00%)	0	1/198 (0.51%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Abdominal pain † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Autoimmune colitis † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Colitis † 1	0/196 (0.00%)	0	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Diarrhoea † 1	1/196 (0.51%)	1	3/198 (1.52%)	3	0/52 (0.00%)	0	0/57 (0.00%)	0
Diverticular perforation † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Faeces discoloured † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Gastric ulcer perforation † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Gastritis † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Gastrointestinal haemorrhage † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Ileus † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Intestinal obstruction † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	1/57 (1.75%)	1
Lip oedema † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Nausea † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Pancreatitis † 1	1/196 (0.51%)	3	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Pancreatitis acute † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Proctitis † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Small intestinal obstruction † 1	0/196 (0.00%)	0	1/198 (0.51%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Vomiting † 1	3/196 (1.53%)	3	3/198 (1.52%)	3	0/52 (0.00%)	0	0/57 (0.00%)	0
General disorders
Asthenia † 1	1/196 (0.51%)	1	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Chest discomfort † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Chest pain † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Death † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	2/57 (3.51%)	2
Fatigue † 1	0/196 (0.00%)	0	3/198 (1.52%)	3	0/52 (0.00%)	0	0/57 (0.00%)	0
General physical health deterioration † 1	1/196 (0.51%)	1	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Influenza like illness † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Non-cardiac chest pain † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Pain † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Pyrexia † 1	0/196 (0.00%)	0	2/198 (1.01%)	2	1/52 (1.92%)	1	0/57 (0.00%)	0
Systemic inflammatory response syndrome † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Hepatobiliary disorders
Cholangitis † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Drug-induced liver injury † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Jaundice † 1	0/196 (0.00%)	0	1/198 (0.51%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Infections and infestations
Bronchitis † 1	0/196 (0.00%)	0	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Clostridium difficile colitis † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Clostridium difficile infection † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Cytomegalovirus infection † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Device related sepsis † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Lower respiratory tract infection † 1	0/196 (0.00%)	0	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Lung abscess † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Myelitis † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Neutropenic sepsis † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Pneumonia † 1	10/196 (5.10%)	11	12/198 (6.06%)	15	4/52 (7.69%)	5	4/57 (7.02%)	7
Pulmonary sepsis † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Pyopneumothorax † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Respiratory tract infection † 1	1/196 (0.51%)	1	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Sepsis † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Septic shock † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Upper respiratory tract infection † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Urinary tract infection † 1	2/196 (1.02%)	2	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Injury, poisoning and procedural complications
Femur fracture † 1	1/196 (0.51%)	1	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Head injury † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Infusion related reaction † 1	2/196 (1.02%)	2	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Limb injury † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Radiation oesophagitis † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Thoracic vertebral fracture † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/196 (0.51%)	1	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Aspartate aminotransferase increased † 1	1/196 (0.51%)	1	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Blood alkaline phosphatase increased † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Blood bilirubin increased † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Blood creatinine increased † 1	0/196 (0.00%)	0	1/198 (0.51%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
C-reactive protein increased † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Liver function test increased † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Neutrophil count decreased † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	2/52 (3.85%)	2	2/57 (3.51%)	2
Platelet count decreased † 1	2/196 (1.02%)	2	0/198 (0.00%)	0	1/52 (1.92%)	1	4/57 (7.02%)	4
Transaminases increased † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
White blood cell count decreased † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Metabolism and nutrition disorders
Decreased appetite † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	1/52 (1.92%)	1	0/57 (0.00%)	0
Dehydration † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Electrolyte imbalance † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Hyperglycaemia † 1	0/196 (0.00%)	0	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Hypokalaemia † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Hypomagnesaemia † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Hyponatraemia † 1	4/196 (2.04%)	4	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Muscular weakness † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Myalgia † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Pain in extremity † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Paraneoplastic syndrome † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Plasma cell myeloma † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Tumour pain † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Nervous system disorders
Cerebral infarction † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	1/52 (1.92%)	1	0/57 (0.00%)	0
Cerebrovascular accident † 1	1/196 (0.51%)	1	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Dysarthria † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Guillain-Barre syndrome † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Neuropathy peripheral † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Somnolence † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Spinal cord oedema † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Syncope † 1	0/196 (0.00%)	0	3/198 (1.52%)	3	0/52 (0.00%)	0	0/57 (0.00%)	0
Transient ischaemic attack † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Trigeminal neuralgia † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Psychiatric disorders
Alcohol abuse † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Depression † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/196 (0.00%)	0	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Tubulointerstitial nephritis † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	2/196 (1.02%)	2	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Asthma † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Bronchial obstruction † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Chronic obstructive pulmonary disease † 1	2/196 (1.02%)	3	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Dyspnoea † 1	2/196 (1.02%)	2	1/198 (0.51%)	1	1/52 (1.92%)	1	0/57 (0.00%)	0
Haemoptysis † 1	1/196 (0.51%)	1	2/198 (1.01%)	2	1/52 (1.92%)	1	0/57 (0.00%)	0
Hypercapnia † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Pleural effusion † 1	1/196 (0.51%)	1	2/198 (1.01%)	2	0/52 (0.00%)	0	0/57 (0.00%)	0
Pneumonitis † 1	2/196 (1.02%)	2	2/198 (1.01%)	4	0/52 (0.00%)	0	2/57 (3.51%)	2
Pneumothorax † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Pulmonary embolism † 1	2/196 (1.02%)	2	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Pulmonary oedema † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Respiratory failure † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	1/57 (1.75%)	1
Skin toxicity † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Vascular disorders
Peripheral arterial occlusive disease † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Peripheral artery occlusion † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	0/57 (0.00%)	0
Superior vena cava syndrome † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
Venous thrombosis limb † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	0/52 (0.00%)	0	0/57 (0.00%)	0
1 Term from vocabulary, MedDRA version 25.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo + Carboplatin + Etoposide - Global		Atezolizumab + Carboplatin + Etoposide - Global		Placebo + Carboplatin + Etoposide - China		Atezolizumab + Carboplatin + Etoposide - China
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	187/196 (95.41%)		191/198 (96.46%)		52/52 (100.00%)		56/57 (98.25%)
Blood and lymphatic system disorders
Anaemia † 1	69/196 (35.20%)	84	86/198 (43.43%)	101	40/52 (76.92%)	50	46/57 (80.70%)	76
Leukopenia † 1	19/196 (9.69%)	32	24/198 (12.12%)	44	14/52 (26.92%)	22	9/57 (15.79%)	24
Neutropenia † 1	66/196 (33.67%)	105	71/198 (35.86%)	122	17/52 (32.69%)	41	11/57 (19.30%)	32
Thrombocytopenia † 1	29/196 (14.80%)	44	31/198 (15.66%)	46	16/52 (30.77%)	31	17/57 (29.82%)	27
Cardiac disorders
Sinus tachycardia † 1	1/196 (0.51%)	2	2/198 (1.01%)	2	4/52 (7.69%)	4	1/57 (1.75%)	1
Endocrine disorders
Hyperthyroidism † 1	5/196 (2.55%)	5	11/198 (5.56%)	11	0/52 (0.00%)	0	2/57 (3.51%)	2
Hypothyroidism † 1	1/196 (0.51%)	1	20/198 (10.10%)	20	2/52 (3.85%)	2	8/57 (14.04%)	9
Gastrointestinal disorders
Abdominal distension † 1	2/196 (1.02%)	2	5/198 (2.53%)	5	1/52 (1.92%)	1	3/57 (5.26%)	3
Abdominal pain † 1	11/196 (5.61%)	11	10/198 (5.05%)	10	0/52 (0.00%)	0	0/57 (0.00%)	0
Constipation † 1	58/196 (29.59%)	70	52/198 (26.26%)	65	8/52 (15.38%)	12	10/57 (17.54%)	19
Diarrhoea † 1	30/196 (15.31%)	46	34/198 (17.17%)	46	2/52 (3.85%)	2	4/57 (7.02%)	5
Nausea † 1	65/196 (33.16%)	95	77/198 (38.89%)	112	10/52 (19.23%)	15	21/57 (36.84%)	47
Stomatitis † 1	9/196 (4.59%)	9	11/198 (5.56%)	11	1/52 (1.92%)	1	1/57 (1.75%)	1
Vomiting † 1	34/196 (17.35%)	49	40/198 (20.20%)	52	7/52 (13.46%)	7	14/57 (24.56%)	20
General disorders
Asthenia † 1	20/196 (10.20%)	26	25/198 (12.63%)	29	4/52 (7.69%)	5	4/57 (7.02%)	4
Chest discomfort † 1	5/196 (2.55%)	5	2/198 (1.01%)	2	2/52 (3.85%)	2	5/57 (8.77%)	5
Chest pain † 1	14/196 (7.14%)	14	18/198 (9.09%)	22	4/52 (7.69%)	4	5/57 (8.77%)	5
Fatigue † 1	51/196 (26.02%)	67	52/198 (26.26%)	66	0/52 (0.00%)	0	6/57 (10.53%)	8
Oedema peripheral † 1	7/196 (3.57%)	8	13/198 (6.57%)	14	0/52 (0.00%)	0	1/57 (1.75%)	1
Pyrexia † 1	16/196 (8.16%)	18	20/198 (10.10%)	32	4/52 (7.69%)	7	13/57 (22.81%)	19
Hepatobiliary disorders
Hepatic function abnormal † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	3/52 (5.77%)	3	3/57 (5.26%)	3
Infections and infestations
Nasopharyngitis † 1	2/196 (1.02%)	2	4/198 (2.02%)	5	4/52 (7.69%)	4	3/57 (5.26%)	3
Upper respiratory tract infection † 1	17/196 (8.67%)	20	15/198 (7.58%)	19	2/52 (3.85%)	2	3/57 (5.26%)	3
Urinary tract infection † 1	6/196 (3.06%)	6	13/198 (6.57%)	18	5/52 (9.62%)	5	2/57 (3.51%)	5
Injury, poisoning and procedural complications
Infusion related reaction † 1	8/196 (4.08%)	9	10/198 (5.05%)	13	1/52 (1.92%)	1	1/57 (1.75%)	1
Investigations
Alanine aminotransferase increased † 1	6/196 (3.06%)	6	6/198 (3.03%)	13	10/52 (19.23%)	15	13/57 (22.81%)	21
Aspartate aminotransferase increased † 1	5/196 (2.55%)	7	8/198 (4.04%)	9	9/52 (17.31%)	16	11/57 (19.30%)	15
Blood alkaline phosphatase increased † 1	3/196 (1.53%)	3	8/198 (4.04%)	8	3/52 (5.77%)	4	1/57 (1.75%)	2
Blood bilirubin increased † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	5/52 (9.62%)	6	2/57 (3.51%)	2
Blood cholesterol increased † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	4/52 (7.69%)	4	8/57 (14.04%)	23
Blood creatinine increased † 1	3/196 (1.53%)	3	7/198 (3.54%)	13	3/52 (5.77%)	3	4/57 (7.02%)	8
Blood glucose increased † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	3/52 (5.77%)	3	3/57 (5.26%)	3
Blood triglycerides increased † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	4/52 (7.69%)	5	6/57 (10.53%)	18
Electrocardiogram QT prolonged † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	3/52 (5.77%)	4	1/57 (1.75%)	1
Gamma-glutamyltransferase increased † 1	1/196 (0.51%)	1	1/198 (0.51%)	4	4/52 (7.69%)	4	2/57 (3.51%)	2
Haemoglobin decreased † 1	3/196 (1.53%)	3	1/198 (0.51%)	1	0/52 (0.00%)	0	4/57 (7.02%)	6
Neutrophil count decreased † 1	45/196 (22.96%)	80	37/198 (18.69%)	74	33/52 (63.46%)	85	41/57 (71.93%)	107
Platelet count decreased † 1	30/196 (15.31%)	41	26/198 (13.13%)	38	14/52 (26.92%)	26	24/57 (42.11%)	40
Protein urine present † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	3/52 (5.77%)	4	1/57 (1.75%)	1
Weight decreased † 1	10/196 (5.10%)	11	21/198 (10.61%)	21	6/52 (11.54%)	6	10/57 (17.54%)	10
Weight increased † 1	6/196 (3.06%)	7	3/198 (1.52%)	3	4/52 (7.69%)	4	1/57 (1.75%)	1
White blood cell count decreased † 1	24/196 (12.24%)	43	18/198 (9.09%)	35	29/52 (55.77%)	73	34/57 (59.65%)	101
Metabolism and nutrition disorders
Decreased appetite † 1	41/196 (20.92%)	45	55/198 (27.78%)	64	12/52 (23.08%)	16	13/57 (22.81%)	22
Diabetes mellitus † 1	0/196 (0.00%)	0	1/198 (0.51%)	1	3/52 (5.77%)	3	0/57 (0.00%)	0
Hyperglycaemia † 1	5/196 (2.55%)	7	9/198 (4.55%)	13	2/52 (3.85%)	3	4/57 (7.02%)	4
Hypertriglyceridaemia † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	0/52 (0.00%)	0	3/57 (5.26%)	3
Hypoalbuminaemia † 1	2/196 (1.02%)	2	3/198 (1.52%)	5	5/52 (9.62%)	5	9/57 (15.79%)	14
Hypochloraemia † 1	2/196 (1.02%)	3	0/198 (0.00%)	0	4/52 (7.69%)	7	5/57 (8.77%)	6
Hypokalaemia † 1	17/196 (8.67%)	18	9/198 (4.55%)	9	5/52 (9.62%)	10	5/57 (8.77%)	8
Hypomagnesaemia † 1	10/196 (5.10%)	10	13/198 (6.57%)	19	2/52 (3.85%)	3	1/57 (1.75%)	1
Hyponatraemia † 1	12/196 (6.12%)	14	10/198 (5.05%)	10	11/52 (21.15%)	17	10/57 (17.54%)	12
Hypoproteinaemia † 1	0/196 (0.00%)	0	0/198 (0.00%)	0	3/52 (5.77%)	4	4/57 (7.02%)	4
Musculoskeletal and connective tissue disorders
Arthralgia † 1	22/196 (11.22%)	29	25/198 (12.63%)	31	4/52 (7.69%)	4	1/57 (1.75%)	1
Back pain † 1	18/196 (9.18%)	20	19/198 (9.60%)	19	0/52 (0.00%)	0	3/57 (5.26%)	3
Pain in extremity † 1	8/196 (4.08%)	9	13/198 (6.57%)	13	2/52 (3.85%)	2	2/57 (3.51%)	2
Nervous system disorders
Dizziness † 1	11/196 (5.61%)	14	20/198 (10.10%)	23	2/52 (3.85%)	2	2/57 (3.51%)	2
Headache † 1	23/196 (11.73%)	26	25/198 (12.63%)	30	3/52 (5.77%)	3	3/57 (5.26%)	3
Psychiatric disorders
Insomnia † 1	14/196 (7.14%)	14	16/198 (8.08%)	19	3/52 (5.77%)	9	4/57 (7.02%)	8
Renal and urinary disorders
Proteinuria † 1	1/196 (0.51%)	1	0/198 (0.00%)	0	7/52 (13.46%)	10	2/57 (3.51%)	3
Respiratory, thoracic and mediastinal disorders
Cough † 1	28/196 (14.29%)	33	22/198 (11.11%)	28	10/52 (19.23%)	12	14/57 (24.56%)	20
Dyspnoea † 1	17/196 (8.67%)	18	21/198 (10.61%)	24	2/52 (3.85%)	2	2/57 (3.51%)	2
Haemoptysis † 1	12/196 (6.12%)	12	14/198 (7.07%)	20	5/52 (9.62%)	6	4/57 (7.02%)	4
Oropharyngeal pain † 1	5/196 (2.55%)	6	13/198 (6.57%)	17	0/52 (0.00%)	0	2/57 (3.51%)	2
Productive cough † 1	9/196 (4.59%)	14	10/198 (5.05%)	10	5/52 (9.62%)	5	7/57 (12.28%)	7
Skin and subcutaneous tissue disorders
Alopecia † 1	69/196 (35.20%)	72	73/198 (36.87%)	75	18/52 (34.62%)	18	25/57 (43.86%)	26
Pruritus † 1	9/196 (4.59%)	10	15/198 (7.58%)	17	1/52 (1.92%)	1	2/57 (3.51%)	3
Rash † 1	13/196 (6.63%)	15	15/198 (7.58%)	25	1/52 (1.92%)	1	6/57 (10.53%)	9
Rash maculo-papular † 1	2/196 (1.02%)	3	11/198 (5.56%)	11	0/52 (0.00%)	0	0/57 (0.00%)	0
Vascular disorders
Hypertension † 1	6/196 (3.06%)	8	15/198 (7.58%)	20	2/52 (3.85%)	2	0/57 (0.00%)	0
1 Term from vocabulary, MedDRA version 25.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. doi: 10.1200/JCO.20.01055. Epub 2021 Jan 13.

Mansfield AS, Kazarnowicz A, Karaseva N, Sanchez A, De Boer R, Andric Z, Reck M, Atagi S, Lee JS, Garassino M, Liu SV, Horn L, Wen X, Quach C, Yu W, Kabbinavar F, Lam S, Morris S, Califano R. Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Ann Oncol. 2020 Feb;31(2):310-317. doi: 10.1016/j.annonc.2019.10.021. Epub 2019 Dec 9.

Nishio M, Sugawara S, Atagi S, Akamatsu H, Sakai H, Okamoto I, Takayama K, Hayashi H, Nakagawa Y, Kawakami T. Subgroup Analysis of Japanese Patients in a Phase III Study of Atezolizumab in Extensive-stage Small-cell Lung Cancer (IMpower133). Clin Lung Cancer. 2019 Nov;20(6):469-476.e1. doi: 10.1016/j.cllc.2019.07.005. Epub 2019 Jul 31.

Horn L, Mansfield AS, Szczesna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. doi: 10.1056/NEJMoa1809064. Epub 2018 Sep 25.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02763579
• Other Study ID Numbers: GO30081; 2015-004861-97 ( EudraCT Number )
• First Submitted: May 4, 2016
• First Posted: May 5, 2016
• Results First Submitted: April 19, 2019
• Results First Posted: June 13, 2019
• Last Update Posted: July 28, 2023