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Clinical Trial Results:
A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel or Atezolizumab in Combination With Carboplatin+Nab-Paclitaxel Versus Carboplatin+Nab-Paclitaxel in Chemotherapy-Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer

Summary
EudraCT number	2014-003208-59
Trial protocol	IT LV DE AT BE ES NL LT BG PT FR SK
Global end of trial date	17 Feb 2021

Results information
Results version number	v3(current)
This version publication date	18 Apr 2022
First version publication date	13 Oct 2019
Other versions	v1 , v2
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GO29437

ISRCTN number

US NCT number

NCT02367794

WHO universal trial number (UTN)

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com

Scientific contact

F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

17 Feb 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Feb 2021

Was the trial ended prematurely?

Main objective of the trial

The main objective of this randomized, Phase III, multicenter, open-label study was to evaluate the safety and efficacy of atezolizumab in combination with carboplatin + paclitaxel or with carboplatin + nab-paclitaxel compared with treatment with carboplatin + nab-paclitaxel in approximately 1025 chemotherapy-naive patients with Stage IV squamous non-small cell lung cancer (NSCLC).

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Jun 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 12

Country: Number of subjects enrolled

Australia: 33

Country: Number of subjects enrolled

Austria: 3

Country: Number of subjects enrolled

Belgium: 16

Country: Number of subjects enrolled

Bulgaria: 9

Country: Number of subjects enrolled

Brazil: 27

Country: Number of subjects enrolled

Canada: 16

Country: Number of subjects enrolled

Chile: 20

Country: Number of subjects enrolled

Germany: 72

Country: Number of subjects enrolled

Spain: 142

Country: Number of subjects enrolled

France: 35

Country: Number of subjects enrolled

Israel: 21

Country: Number of subjects enrolled

Italy: 37

Country: Number of subjects enrolled

Japan: 83

Country: Number of subjects enrolled

Lithuania: 1

Country: Number of subjects enrolled

Latvia: 12

Country: Number of subjects enrolled

Mexico: 4

Country: Number of subjects enrolled

Netherlands: 16

Country: Number of subjects enrolled

Peru: 6

Country: Number of subjects enrolled

Portugal: 12

Country: Number of subjects enrolled

Russian Federation: 35

Country: Number of subjects enrolled

Singapore: 12

Country: Number of subjects enrolled

Slovakia: 6

Country: Number of subjects enrolled

Taiwan: 12

Country: Number of subjects enrolled

Ukraine: 178

Country: Number of subjects enrolled

United States: 201

Worldwide total number of subjects

1021

EEA total number of subjects

361

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

476

From 65 to 84 years

543

85 years and over

Subject disposition

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Recruitment details

'Study Terminated By Sponsor' Reason for Not Completed is a data entry error; reason for not completed is unknown. The study was Completed and not Terminated.

Screening details

Participants in this study included chemotherapy-naive patients with Stage IV squamous non-small cell lung cancer (NSCLC).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Arm C: Nab-Paclitaxel + Carboplatin

Arm description

The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Participants who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, participants received best supportive care.

Arm type

Active comparator

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles.

Investigational medicinal product name

Nab-Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nab-paclitaxel 100 milligrams per meter squared (mg/m^2) IV on Day 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles.

Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Arm description

The induction phase of the study consisted of four or six cycles; atezolizumab and carboplatin were administered on Day 1 of each 21-day cycle. Nab-Paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then nab-paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab 1200 milligrams (mg) intravenous infusion (IV) on day 1 of each 21-day cycle.

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles.

Investigational medicinal product name

Nab-Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Nab-paclitaxel 100 milligrams per meter squared (mg/m^2) IV on Day 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles.

Arm A: Atezolizumab + Paclitaxel + Carboplatin

Arm description

The induction phase of the study consisted of four or six cycles; atezolizumab, paclitaxel, and carboplatin were administered on Day 1 of each 21-day cycle. The Day 1 order of drug administration was as follows: atezolizumab, then paclitaxel, then carboplatin. Participants who experienced no further clinical benefit at any time during the induction phase discontinued all study treatments. In the absence of the above criteria, after the 4- or 6-cycle induction phase, participants began maintenance therapy with atezolizumab. Atezolizumab was continued as long as there was clinical benefit to the participant.

Arm type

Experimental

Investigational medicinal product name

Atezolizumab

Investigational medicinal product code

Other name

Tecentriq

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Atezolizumab 1200 milligrams (mg) intravenous infusion (IV) on day 1 of each 21-day cycle.

Investigational medicinal product name

Paclitaxel

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Paclitaxel 200 mg/m^2 IV on Day 1 of each 21-day cycle for 4 or 6 cycles. Participants of Asian race/ethnicity will be administered paclitaxel 175 mg/m2 IV.

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles.

Number of subjects in period 1	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Started	340	343	338
Completed	0	0	0
Not completed	340	343	338
Adverse event, serious fatal	252	245	243
Randomized in error	-	-	1
Physician decision	-	5	3
Discontinuation Matched Treatment Discontinuation	-	-	1
Patient unable to receive carboplatin	-	-	1
Investigational Product in Commercial Stock	-	1	-
Moved to Commercial Atezolizumab Use	-	2	1
Brain metastasis	1	-	-
Consent withdrawn by subject	25	12	20
Moved to Roll-Over Study	-	15	13
Study Terminated By Sponsor	-	1	1
Adverse event, non-fatal	-	-	2
Participant Enrolled in Extended Protocol	-	1	-
Lost to follow-up	1	2	2
Sponsor Request	60	57	45
Moved into PTAP Study	-	2	3
Protocol deviation	1	-	1
Hypercalcemia prior to C1D1	-	-	1

Baseline characteristics

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Reporting group title

Arm C: Nab-Paclitaxel + Carboplatin

Reporting group description

Reporting group title

Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Reporting group description

Reporting group title

Arm A: Atezolizumab + Paclitaxel + Carboplatin

Reporting group description

Reporting group values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin	Total
Number of subjects	340	343	338	1021
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	0	0	0	0
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	156	170	150	476
From 65-84 years	183	173	187	543
85 years and over	1	0	1	2
Age Continuous
Units: Years
arithmetic mean (standard deviation)	64.9 ± 8.1	64.0 ± 9.2	65.0 ± 8.3	-
Sex: Female, Male
Units: Participants
Female	63	63	60	186
Male	277	280	278	835
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	24	27	28	79
Not Hispanic or Latino	299	306	297	902
Unknown or Not Reported	17	10	13	40
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	1	1	3	5
Asian	37	41	34	112
Native Hawaiian or Other Pacific Islander	0	0	1	1
Black or African American	7	4	3	14
White	290	289	290	869
More than one race	1	6	1	8
Unknown or Not Reported	4	2	6	12

End points

Top of page

Reporting group title

Arm C: Nab-Paclitaxel + Carboplatin

Reporting group description

Reporting group title

Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Reporting group description

Reporting group title

Arm A: Atezolizumab + Paclitaxel + Carboplatin

Reporting group description

Primary: Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population

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End point title

Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population

End point description

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT population.

End point type

Primary

End point timeframe

Up to approximately 30 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	340	343	338
Units: Months
median (confidence interval 95%)	5.6 (5.5 to 5.7)	6.5 (5.7 to 7.1)	5.6 (5.5 to 6.9)

PFS in ITT

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

683

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0006

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.75

Confidence interval

level

95%

sides

2-sided

lower limit

0.64

upper limit

0.88

Primary: Overall Survival (OS) in the ITT Population

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End point title

Overall Survival (OS) in the ITT Population

End point description

OS is defined as the time between the date of randomization and date of death from any cause in the ITT population.

End point type

Primary

End point timeframe

Up to approximately 39 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	340	343	338
Units: Months
median (confidence interval 95%)	13.5 (12.2 to 15.1)	14.2 (12.3 to 16.8)	12.6 (11.6 to 14.7)

OS in ITT

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

683

Analysis specification

Pre-specified

Analysis type

P-value

= 0.1581

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.05

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population

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End point title

PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population

End point description

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population.

End point type

Secondary

End point timeframe

Up to approximately 30 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	108	115	100
Units: Months
median (confidence interval 95%)	5.6 (5.1 to 5.7)	8.4 (6.8 to 10.4)	7.0 (5.6 to 8.3)

PFS in TC 2/3 or IC 2/3 Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

^[1]

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.4

upper limit

0.72

Notes
[1] - Unstratified Analysis

PFS in TC 2/3 or IC 2/3 Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

^[2]

P-value

= 0.0018

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.45

upper limit

0.84

Notes
[2] - Unstratified Analysis

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population

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End point title

PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population

End point description

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the TC1/2/3 or IC1/2/3 Population.

End point type

Secondary

End point timeframe

Up to approximately 30 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	169	182	167
Units: Months
median (confidence interval 95%)	5.6 (5.3 to 5.7)	7.1 (5.8 to 8.3)	7.0 (5.6 to 8.3)

PFS in TC 1/2/3 or IC 1/2/3 Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

^[3]

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

0.77

Notes
[3] - Unstratified Analysis

PFS in TC 1/2/3 or IC 1/2/3 Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

351

Analysis specification

Pre-specified

Analysis type

^[4]

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.48

upper limit

0.77

Notes
[4] - Unstratified Analysis

Secondary: OS in the TC2/3 or IC2/3 Population

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End point title

OS in the TC2/3 or IC2/3 Population

End point description

OS is defined as the time between the date of randomization and date of death from any cause, in the TC2/3 or IC2/3 Population.

End point type

Secondary

End point timeframe

Up to approximately 39 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	108	115	100
Units: Months
median (confidence interval 95%)	14.5 (12.1 to 17.2)	20.4 (13.8 to 24.1)	14.8 (11.1 to 23.7)

OS in TC 2/3 or IC 2/3 Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

^[5]

P-value

= 0.0518

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.725

Confidence interval

level

95%

sides

2-sided

lower limit

0.524

upper limit

1.004

Notes
[5] - Unstratified Analysis

OS in TC 2/3 or IC 2/3 Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

223

Analysis specification

Pre-specified

Analysis type

^[6]

P-value

= 0.2841

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.832

Confidence interval

level

95%

sides

2-sided

lower limit

0.594

upper limit

1.165

Notes
[6] - Unstratified Analysis

Secondary: OS in the TC1/2/3 or IC1/2/3 Population

Top of page

End point title

OS in the TC1/2/3 or IC1/2/3 Population

End point description

OS is defined as the time between the date of randomization and date of death from any cause in the TC1/2/3 or IC1/2/3 Population.

End point type

Secondary

End point timeframe

Up to approximately 39 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	169	182	167
Units: Months
median (confidence interval 95%)	15.0 (12.4 to 17.2)	14.8 (12.1 to 19.6)	14.9 (12.5 to 18.2)

OS in TC 1/2/3 or IC 1/2/3 Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

351

Analysis specification

Pre-specified

Analysis type

^[7]

P-value

= 0.2473

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.861

Confidence interval

level

95%

sides

2-sided

lower limit

0.668

upper limit

1.109

Notes
[7] - Unstratified Analysis

OS in TC 1/2/3 or IC 1/2/3 Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

336

Analysis specification

Pre-specified

Analysis type

^[8]

P-value

= 0.2956

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.871

Confidence interval

level

95%

sides

2-sided

lower limit

0.671

upper limit

1.129

Notes
[8] - Unstratified Analysis

Secondary: Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

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End point title

Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

End point description

Proportion of participants with an objective response (CR or PR) in the ITT population.

End point type

Secondary

End point timeframe

Up to approximately 30 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	339	342	337
Units: Percentage of participants
number (not applicable)	41.0	49.7	49.3

OR in ITT Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

681

Analysis specification

Pre-specified

Analysis type

^[9]

P-value

= 0.0248

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.04

upper limit

1.91

Notes
[9] - Stratified Analysis

OR in ITT Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

676

Analysis specification

Pre-specified

Analysis type

^[10]

P-value

= 0.0308

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

1.9

Notes
[10] - Stratified Analysis

Secondary: Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

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End point title

Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

End point description

Duration of response is defined as the time from the first documented objective response to documented PD or death from any cause, whichever occurred first, in the ITT Population.

End point type

Secondary

End point timeframe

Up to approximately 30 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	139	170	166
Units: Months
median (confidence interval 95%)	5.2 (4.4 to 5.6)	7.2 (6.8 to 9.5)	7.0 (5.7 to 8.3)

DOR in ITT Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

305

Analysis specification

Pre-specified

Analysis type

^[11]

P-value

= 0.0007

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.64

Confidence interval

level

95%

sides

2-sided

lower limit

0.493

upper limit

0.831

Notes
[11] - Unstratified Analysis

DOR in ITT Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

309

Analysis specification

Pre-specified

Analysis type

^[12]

P-value

< 0.0001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.53

Confidence interval

level

95%

sides

2-sided

lower limit

0.408

upper limit

0.689

Notes
[12] - Unstratified Analysis

Secondary: Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population

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End point title

Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population

End point description

TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population. The EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC scales and single-item measures will be linearly transformed so that each score has a range of 0-100. A high score for a functional scale represents a high or healthy level of functioning, and a high score for the global health status and HRQoL represents a high HRQoL; however, a high score for a symptom scale or item represents a high level of symptomatology or problems.

End point type

Secondary

End point timeframe

Up to approximately 30 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	340	343	338
Units: Months
median (confidence interval 95%)	3.2 (2.6 to 4.1)	4.2 (3.2 to 5.6)	3.0 (2.6 to 3.9)

TTD Using EORTC QLQ-C30 in ITT Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

678

Analysis specification

Pre-specified

Analysis type

^[13]

P-value

= 0.7295

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.834

upper limit

1.296

Notes
[13] - Stratified Analysis

TTD Using EORTC QLQ-C30 in ITT Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

683

Analysis specification

Pre-specified

Analysis type

^[14]

P-value

= 0.0461

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.797

Confidence interval

level

95%

sides

2-sided

lower limit

0.638

upper limit

0.996

Notes
[14] - Stratified Analysis

Secondary: TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population

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End point title

TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population

End point description

TTD was documented for a 3-symptom composite endpoint using the following EORTC QLQ-LC13 symptom scores: cough, chest pain, and dyspnea multi--item scale. In this instance, symptom deterioration will be determined as a >= 10-point increase above baseline in any of the listed symptom scores, whichever occurs first (cough, chest pain, and dyspnea multi-item scale). Confirmed clinically meaningful symptom deterioration will need to be held for the original symptom; a >= 10-point increase above baseline in a symptom score must be held for at least two consecutive assessments or an initial>=10-point increase above baseline followed by death within 3 weeks from the last assessment. A >= 10-point change in the EORTC scale score is perceived by patients as clinically significant.

End point type

Secondary

End point timeframe

Up to approximately 30 months after the first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	340	343	338
Units: Months
median (confidence interval 95%)	2.6 (2.2 to 3.0)	3.4 (2.7 to 5.1)	2.8 (2.1 to 3.7)

TTD Using EORTC QLQ-LC13 in ITT Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

678

Analysis specification

Pre-specified

Analysis type

^[15]

P-value

= 0.7692

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.968

Confidence interval

level

95%

sides

2-sided

lower limit

0.779

upper limit

1.203

Notes
[15] - Unstratified Analysis

TTD Using EORTC QLQ-LC13 in ITT Population

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

683

Analysis specification

Pre-specified

Analysis type

^[16]

P-value

= 0.0906

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.828

Confidence interval

level

95%

sides

2-sided

lower limit

0.666

upper limit

1.031

Notes
[16] - Unstratified Analysis

Secondary: Change from Baseline in Patient-reported Lung Cancer Symptoms Score using the SILC Scale Symptom Severity Score in the ITT Population

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End point title

Change from Baseline in Patient-reported Lung Cancer Symptoms Score using the SILC Scale Symptom Severity Score in the ITT Population

End point description

Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for chest pain score is considered to be clinically significant. (Note: PD=progression of disease. FU=follow up. Note: 999999=not available.)

End point type

Secondary

End point timeframe

Baseline up to approximately 30 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	189	215	195
Units: Units on a scale
arithmetic mean (standard deviation)
Chest Pain, Week 1 (n=171, 192,166)	0.04 ± 0.93	0.14 ± 0.87	0.44 ± 1.03
Chest Pain, Week 2 (n=160, 186, 165)	-0.08 ± 0.89	0.09 ± 0.98	0.28 ± 1.00
Chest Pain, Week 3 (n=165, 175, 165)	-0.14 ± 0.95	-0.03 ± 0.78	-0.05 ± 1.00
Chest Pain, Week 4 (n=157, 173, 169)	-0.19 ± 0.98	-0.05 ± 0.98	0.09 ± 1.12
Chest Pain, Week 5 (n=160, 172, 159)	-0.17 ± 1.10	-0.08 ± 0.99	-0.16 ± 1.09
Chest Pain, Week 6 (n=151, 170, 161)	-0.35 ± 1.08	-0.13 ± 0.99	-0.20 ± 1.02
Chest Pain, Week 7 (n=138, 166, 143)	-0.38 ± 1.12	-0.18 ± 0.92	-0.14 ± 1.16
Chest Pain, Week 8 (n=140, 162, 152)	-0.35 ± 1.12	-0.17 ± 1.02	-0.17 ± 1.09
Chest Pain, Week 9 (n=135, 162, 143)	-0.36 ± 1.00	-0.19 ± 0.97	-0.21 ± 1.10
Chest Pain, Week 10 (n=133, 158, 146)	-0.20 ± 1.09	-0.16 ± 1.00	-0.08 ± 1.19
Chest Pain, Week 11 (n=132, 157, 137)	-0.27 ± 1.08	-0.24 ± 0.91	-0.09 ± 1.16
Chest Pain, Week 12 (n=128, 151, 136)	-0.34 ± 1.05	-0.21 ± 1.01	-0.30 ± 1.05
Chest Pain, Week 13 (n=117, 144, 130)	-0.31 ± 1.24	-0.22 ± 1.02	-0.17 ± 1.10
Chest Pain, Week 14 (n=105, 139, 138)	-0.32 ± 1.18	-0.24 ± 0.88	-0.15 ± 1.13
Chest Pain, Week 15 (n=97, 143, 132)	-0.45 ± 1.19	-0.28 ± 0.99	-0.17 ± 1.00
Chest Pain, Week 16 (n=102, 138, 121)	-0.28 ± 1.10	-0.14 ± 1.00	-0.23 ± 1.10
Chest Pain, Week 17 (n=101, 135, 129)	-0.32 ± 1.11	-0.17 ± 0.99	-0.24 ± 1.10
Chest Pain, Week 18 (n=93, 141, 129)	-0.28 ± 1.08	-0.13 ± 0.99	-0.17 ± 1.09
Chest Pain, Week 19 (n=85, 129, 118)	-0.18 ± 1.09	-0.10 ± 0.99	-0.16 ± 1.07
Chest Pain, Week 20 (n=75, 130, 114)	-0.23 ± 1.07	-0.15 ± 0.94	-0.17 ± 1.13
Chest Pain, Week 21 (n=69, 129, 113)	-0.37 ± 1.02	-0.07 ± 1.02	-0.18 ± 1.14
Chest Pain, Week 22 (n=79, 125, 109)	-0.27 ± 1.18	-0.08 ± 1.01	-0.14 ± 1.16
Chest Pain, Week 23 (n=70, 128, 106)	-0.29 ± 1.16	0.04 ± 0.96	-0.10 ± 1.07
Chest Pain, Week 24 (n=67, 121, 105)	-0.43 ± 1.15	-0.15 ± 0.97	-0.17 ± 1.14
Chest Pain, Week 25 (n=48, 118, 104)	-0.25 ± 1.24	-0.17 ± 1.06	-0.20 ± 1.10
Chest Pain, Week 26 (n=48, 111, 99)	-0.50 ± 1.20	-0.06 ± 1.08	-0.11 ± 1.09
Chest Pain, Week 27 (n=42, 110, 95)	-0.35 ± 1.29	-0.17 ± 1.03	0.04 ± 1.14
Chest Pain, Week 28 (n=41, 103, 88)	-0.22 ± 1.27	-0.12 ± 1.09	-0.19 ± 1.24
Chest Pain, Week 29 (n=38, 100, 89)	-0.30 ± 1.23	-0.11 ± 0.96	-0.18 ± 1.11
Chest Pain, Week 30 (n=46, 104, 86)	-0.15 ± 1.36	-0.21 ± 1.02	-0.08 ± 1.09
Chest Pain, Week 31 (n=35, 97, 77)	-0.49 ± 1.25	-0.16 ± 0.99	-0.15 ± 1.08
Chest Pain, Week 32 (n=29, 91, 70)	-0.29 ± 1.16	-0.15 ± 0.88	-0.16 ± 1.01
Chest Pain, Week 33 (n=29, 93, 68)	-0.29 ± 1.35	-0.20 ± 0.97	-0.10 ± 1.09
Chest Pain, Week 34 (n=33, 92, 73)	-0.15 ± 1.42	-0.04 ± 0.89	0.02 ± 1.16
Chest Pain, Week 35 (n=33, 90, 72)	-0.26 ± 1.31	-0.14 ± 0.88	-0.19 ± 1.09
Chest Pain, Week 36 (n=31, 83, 64)	-0.24 ± 1.34	-0.06 ± 0.88	-0.06 ± 1.12
Chest Pain, Week 37 (n=24, 84, 65)	-0.27 ± 1.37	0.05 ± 1.06	-0.08 ± 1.08
Chest Pain, Week 38 (n=24, 86, 65)	-0.19 ± 1.30	-0.09 ± 0.97	-0.14 ± 1.13
Chest Pain, Week 39 (n=25, 75, 68)	-0.06 ± 1.53	-0.18 ± 0.96	-0.13 ± 1.13
Chest Pain, Week 40 (n=24, 74, 62)	0.06 ± 1.31	-0.11 ± 0.85	-0.06 ± 1.01
Chest Pain, Week 41 (n=22, 69, 60)	0.14 ± 1.21	-0.14 ± 0.92	-0.13 ± 1.05
Chest Pain, Week 42 (n=24, 77, 60)	-0.10 ± 1.50	-0.05 ± 0.94	-0.11 ± 1.02
Chest Pain, Week 43 (n=23, 72, 58)	0.13 ± 1.59	-0.08 ± 0.99	0.05 ± 1.13
Chest Pain, Week 44 (n=20, 93, 60)	-0.08 ± 1.52	-0.25 ± 0.99	-0.10 ± 1.07
Chest Pain, Week 45 (n=20, 64, 51)	0.15 ± 1.70	-0.21 ± 0.97	-0.05 ± 1.20
Chest Pain, Week 46 (n=20, 61, 53)	0.00 ± 1.39	-0.16 ± 1.04	-0.07 ± 1.33
Chest Pain, Week 47 (n=20, 64, 48)	0.18 ± 1.29	-0.16 ± 0.99	0.04 ± 1.29
Chest Pain, Week 48 (n=19, 62, 52)	-0.08 ± 1.53	-0.17 ± 0.97	0.00 ± 1.32
Chest Pain, Week 49 (n=13, 57, 45)	-0.23 ± 1.59	-0.24 ± 1.05	-0.09 ± 1.31
Chest Pain, Week 50 (n=15, 60, 45)	0.00 ± 1.73	-0.17 ± 0.98	-0.14 ± 1.36
Chest Pain, Week 51 (n=11, 58, 37)	0.55 ± 1.39	-0.16 ± 1.07	-0.19 ± 1.24
Chest Pain, Week 52 (n=13, 58, 43)	0.15 ± 1.30	-0.09 ± 0.98	0.02 ± 1.30
Chest Pain, Week 53 (n=14, 53, 35)	0.18 ± 1.27	-0.12 ± 0.95	-0.20 ± 1.22
Chest Pain, Week 54 (n=13, 56, 36)	0.08 ± 1.17	-0.18 ± 0.92	-0.24 ± 1.34
Chest Pain, Week 55 (n=12, 47, 36)	0.21 ± 1.37	-0.11 ± 0.79	-0.15 ± 1.19
Chest Pain, Week 56 (n=11, 50, 36)	0.05 ± 1.39	-0.22 ± 0.91	-0.08 ± 1.36
Chest Pain, Week 57 (n=10, 52, 33)	0.05 ± 1.46	-0.22 ± 0.95	-0.27 ± 1.22
Chest Pain, Week 58 (n=8, 45, 29)	0.13 ± 1.25	-0.22 ± 0.86	-0.24 ± 1.12
Chest Pain, Week 59 (n=11, 47, 27)	0.00 ± 1.32	-0.20 ± 1.01	-0.28 ± 1.17
Chest Pain, Week 60 (n=11, 41, 31)	0.09 ± 1.59	-0.27 ± 0.97	-0.26 ± 1.22
Chest Pain, Week 61 (n=9, 40, 28)	0.61 ± 1.29	-0.23 ± 0.83	-0.34 ± 1.23
Chest Pain, Week 62 (n=10, 39, 25)	0.05 ± 1.34	-0.03 ± 1.00	-0.36 ± 0.96
Chest Pain, Week 63 (n=8, 42, 22)	-0.44 ± 1.21	-0.12 ± 0.92	-0.55 ± 1.13
Chest Pain, Week 64 (n=8, 42, 18)	0.19 ± 1.49	-0.13 ± 0.99	-0.42 ± 1.33
Chest Pain, Week 65 (n=6, 39, 20)	0.25 ± 1.37	-0.13 ± 0.95	-0.25 ± 1.21
Chest Pain, Week 66 (n=6, 37, 19)	0.42 ± 1.53	0.00 ± 1.26	-0.47 ± 1.18
Chest Pain, Week 67 (n=5, 33, 20)	-0.50 ± 1.27	-0.08 ± 1.04	-0.43 ± 1.27
Chest Pain, Week 68 (n=6, 33, 19)	0.08 ± 1.77	-0.09 ± 1.02	-0.53 ± 1.23
Chest Pain, Week 69 (n=5, 31, 18)	0.70 ± 1.60	-0.15 ± 1.08	-0.03 ± 1.14
Chest Pain, Week 70 (n=5, 32, 19)	0.30 ± 1.79	-0.06 ± 0.97	-0.32 ± 1.08
Chest Pain, Week 71 (n=6, 27, 15)	0.08 ± 1.72	-0.13 ± 0.91	-0.43 ± 1.22
Chest Pain, Week 72 (n=6, 27, 18)	0.25 ± 1.70	-0.20 ± 0.94	-0.14 ± 1.00
Chest Pain, Week 73 (n=6, 27, 13)	0.42 ± 1.53	-0.02 ± 1.09	-0.08 ± 1.27
Chest Pain, Week 74 (n=7, 29, 12)	0.43 ± 1.62	-0.10 ± 1.14	-0.38 ± 1.21
Chest Pain, Week 75 (n=6, 24, 12)	0.25 ± 1.70	-0.17 ± 0.89	-0.21 ± 1.18
Chest Pain, Week 76 (n=6, 23, 14)	0.00 ± 1.76	-0.02 ± 1.03	-0.21 ± 1.25
Chest Pain, Week 77 (n=6, 22, 10)	0.00 ± 1.76	0.00 ± 1.15	-0.05 ± 1.21
Chest Pain, Week 78 (n=7, 22, 11)	0.07 ± 1.62	-0.11 ± 1.11	0.00 ± 1.02
Chest Pain, Week 79 (n=6, 24, 9)	0.08 ± 1.72	-0.13 ± 0.86	0.17 ± 0.94
Chest Pain, Week 80 (n=7, 20, 11)	0.14 ± 1.65	-0.35 ± 0.99	0.09 ± 1.14
Chest Pain, Week 81 (n=6, 18, 9)	0.25 ± 1.70	-0.25 ± 0.90	0.22 ± 0.97
Chest Pain, Week 82 (n=7, 21, 9)	0.07 ± 1.62	-0.31 ± 1.03	0.22 ± 1.12
Chest Pain, Week 83 (n=5, 19, 10)	0.00 ± 1.77	-0.32 ± 1.03	-0.05 ± 1.01
Chest Pain, Week 84 (n=5, 15, 10)	0.00 ± 1.84	-0.33 ± 1.08	0.35 ± 1.00
Chest Pain, Week 85 (n=4, 17, 10)	1.13 ± 1.31	-0.35 ± 1.03	0.30 ± 1.14
Chest Pain, Week 86 (n=3, 15, 6)	1.33 ± 1.53	-0.37 ± 0.95	0.33 ± 1.37
Chest Pain, Week 87 (n=3, 12, 8)	1.00 ± 1.73	-0.25 ± 1.10	0.13 ± 0.99
Chest Pain, Week 88 (n=3, 15, 7)	0.83 ± 1.44	-0.20 ± 1.22	0.00 ± 1.00
Chest Pain, Week 89 (n=3, 14, 7)	0.67 ± 2.08	-0.14 ± 1.08	-0.29 ± 1.25
Chest Pain, Week 90 (n=3, 13, 7)	0.67 ± 2.08	-0.04 ± 1.25	0.00 ± 1.29
Chest Pain, Week 91 (n=3, 13, 7)	1.17 ± 1.61	-0.42 ± 1.13	0.14 ± 1.07
Chest Pain, Week 92 (n=4, 13, 8)	0.88 ± 1.44	-0.15 ± 1.20	0.19 ± 1.25
Chest Pain, Week 93 (n=2, 13, 10)	1.50 ± 2.12	0.00 ± 1.24	-0.05 ± 1.01
Chest Pain, Week 94 (n=3, 11, 8)	0.67 ± 2.08	-0.23 ± 1.35	0.00 ± 1.20
Chest Pain, Week 95 (n=3, 11, 8)	0.67 ± 2.08	0.14 ± 1.19	0.25 ± 1.00
Chest Pain, Week 96 (n=3, 11, 8)	1.17 ± 1.61	0.09 ± 1.53	0.19 ± 0.92
Chest Pain, Week 97 (n=3, 11, 9)	1.17 ± 1.61	-0.18 ± 1.54	-0.11 ± 1.17
Chest Pain, Week 98 (n=3, 10, 7)	0.83 ± 2.02	0.05 ± 1.48	0.00 ± 1.00
Chest Pain, Week 99 (n=3, 10, 7)	0.67 ± 2.08	0.00 ± 1.53	0.07 ± 1.02
Chest Pain, Week 100 (n=2, 10, 8)	1.25 ± 1.77	-0.15 ± 1.43	0.00 ± 1.20
Chest Pain, Week 101 (n=3, 10, 7)	1.17 ± 1.61	-0.10 ± 1.54	0.21 ± 0.99
Chest Pain, Week 102 (n=3, 6, 6)	1.00 ± 1.32	-0.25 ± 0.88	0.08 ± 1.11
Chest Pain, Week 103 (n=2, 9, 6)	-0.50 ± 0.71	-0.56 ± 1.04	0.17 ± 1.17
Chest Pain, Week 104 (n=2, 8, 4)	0.25 ± 0.35	-0.56 ± 1.05	0.00 ± 1.41
Chest Pain, Week 105 (n=2, 6, 6)	0.50 ± 0.00	-0.50 ± 0.84	0.00 ± 1.10
Chest Pain, Week 106 (n=2, 9, 5)	0.00 ± 0.00	-0.72 ± 1.06	-0.40 ± 1.14
Chest Pain, Week 107 (n=2, 7, 4)	0.25 ± 0.35	-0.57 ± 1.17	-0.50 ± 0.58
Chest Pain, Week 108 (n=2, 5, 4)	0.25 ± 0.35	-0.30 ± 1.25	-0.38 ± 0.75
Chest Pain, Week 109 (n=2, 5, 2)	-0.50 ± 0.71	-0.90 ± 1.24	0.25 ± 1.77
Chest Pain, Week 110 (n=2, 3, 4)	0.00 ± 0.71	-0.50 ± 1.32	-0.38 ± 1.11
Chest Pain, Week 111 (n=2, 4, 4)	0.25 ± 0.35	-0.25 ± 1.26	-0.38 ± 0.48
Chest Pain, Week 112 (n=2, 3, 2)	0.50 ± 0.00	-0.67 ± 1.15	-1.00 ± 0.00
Chest Pain, Week 113 (n=1, 4, 3)	0.00 ± 999999	-0.50 ± 1.00	-0.67 ± 0.58
Chest Pain, Week 114 (n=2, 3, 2)	-0.25 ± 1.06	-0.50 ± 1.32	-1.00 ± 0.00
Chest Pain, Week 115 (n=2, 4, 3)	-0.25 ± 1.06	-0.50 ± 1.00	-0.67 ± 0.58
Chest Pain, Week 116 (n=2, 3, 3)	-0.50 ± 0.71	-0.67 ± 1.15	-0.67 ± 0.58
Chest Pain, Week 117 (n=2, 2, 2)	-0.25 ± 1.06	-1.00 ± 1.41	-1.00 ± 0.00
Chest Pain, Week 118 (n=1, 1, 2)	0.00 ± 999999	0.00 ± 999999	-1.00 ± 0.00
Chest Pain, Week 119 (n=0, 1, 2)	999999 ± 999999	0.00 ± 999999	-1.00 ± 0.00
Chest Pain, Week 120 (n=0, 1, 2)	999999 ± 999999	0.00 ± 999999	-1.00 ± 0.00
Chest Pain, Week 121 (n=0, 1, 2)	999999 ± 999999	0.00 ± 999999	-1.00 ± 0.00
Chest Pain, Week 122 (n=0, 1, 2)	999999 ± 999999	0.00 ± 999999	-1.00 ± 0.00
Chest Pain, Week 123 (n=0, 1, 1)	999999 ± 999999	0.00 ± 999999	-1.00 ± 999999
Chest Pain, Week 124 (n=0, 1, 1)	999999 ± 999999	0.00 ± 999999	-0.50 ± 999999
Chest Pain, Week 125 (n=0, 0, 1)	999999 ± 999999	999999 ± 999999	-0.50 ± 999999
Chest Pain, Week 126 (n=0, 0, 1)	999999 ± 999999	999999 ± 999999	-0.50 ± 999999
Chest Pain, Week 127 (n=0, 0, 1)	999999 ± 999999	999999 ± 999999	-1.00 ± 999999
Chest Pain, Time of First Pd (n=103, 107, 106)	-0.19 ± 1.13	0.10 ± 1.12	-0.11 ± 1.21
Chest Pain, Time of Last Tx Dose (n=161, 172, 151)	-0.18 ± 1.06	0.01 ± 1.09	0.05 ± 1.14
Chest Pain, Survival FU Month 1 (n=86, 0, 0)	0.03 ± 1.30	-0.10 ± 1.03	-0.08 ± 0.95
Chest Pain, Survival FU Month 2 (n=52, 0, 0)	-0.10 ± 1.23	-0.16 ± 1.04	-0.33 ± 1.07
Chest Pain, Survival FU Month 3 (n=40, 0, 0)	-0.09 ± 1.13	-0.24 ± 1.08	-0.19 ± 1.13
Chest Pain, Survival FU Month 4 (n=32, 0, 0)	-0.13 ± 1.15	-0.22 ± 1.01	-0.35 ± 1.11
Chest Pain, Survival FU Month 5 (n=26, 0, 0)	-0.02 ± 1.34	-0.27 ± 1.07	-0.47 ± 1.11
Chest Pain, Survival FU Month 6 (n=23, 0, 0)	-0.22 ± 0.99	-0.26 ± 0.97	-0.36 ± 1.09
Chest Pain, Survival FU Month 7 (n=3, 0, 0)	0.33 ± 0.58	-0.27 ± 1.01	-0.34 ± 1.09
Chest Pain, Survival FU Month 8 (n=2, 0, 0)	-0.75 ± 1.06	-0.28 ± 1.09	-0.42 ± 1.08
Cough, Week 1 (n=171, 192, 166)	0.01 ± 0.78	0.03 ± 0.82	-0.02 ± 0.74
Cough, Week 2 (n=160, 186, 165)	-0.02 ± 0.91	0.00 ± 0.90	0.17 ± 0.87
Cough, Week 3 (n=165, 175, 165)	-0.09 ± 0.90	-0.10 ± 1.03	-0.08 ± 0.95
Cough, Week 4 (n=157, 173, 169)	-0.26 ± 0.92	-0.16 ± 1.04	-0.33 ± 1.07
Cough, Week 5 (n=160, 172, 159)	-0.18 ± 1.02	-0.24 ± 1.08	-0.19 ± 1.13
Cough, Week 6 (n=151, 170, 161)	-0.27 ± 1.05	-0.22 ± 1.01	-0.35 ± 1.11
Cough, Week 7 (n=138, 166, 143)	-0.27 ± 1.06	-0.27 ± 1.07	-0.47 ± 1.11
Cough, Week 8 (n=140, 162, 152)	-0.26 ± 1.11	-0.26 ± 0.97	-0.36 ± 1.09
Cough, Week 9 (n=135, 162, 143)	-0.32 ± 1.16	-0.27 ± 1.01	-0.34 ± 1.09
Cough, Week 10 (n=133, 158, 146)	-0.28 ± 1.02	-0.28 ± 1.09	-0.42 ± 1.08
Cough, Week 11 (n=132, 157, 137)	-0.31 ± 0.98	-0.27 ± 1.14	-0.50 ± 1.06
Cough, Week 12 (n=128, 151, 136)	-0.30 ± 1.08	-0.25 ± 1.13	-0.46 ± 1.06
Cough, Week 13 (n=117, 144, 130)	-0.23 ± 1.14	-0.28 ± 1.17	-0.46 ± 1.10
Cough, Week 14 (n=105, 139, 138)	-0.31 ± 1.09	-0.29 ± 1.13	-0.50 ± 1.16
Cough, Week 15 (n=97, 143, 132)	-0.39 ± 1.11	-0.23 ± 1.03	-0.47 ± 1.18
Cough, Week 16 (n=102, 138, 121)	-0.19 ± 1.19	-0.18 ± 1.14	-0.52 ± 1.25
Cough, Week 17 (n=101, 135, 129)	-0.18 ± 1.08	-0.21 ± 1.06	-0.48 ± 1.16
Cough, Week 18 (n=93, 141, 129)	-0.26 ± 1.09	-0.34 ± 1.12	-0.48 ± 1.05
Cough, Week 19 (n=85, 129, 118)	-0.29 ± 1.05	-0.29 ± 1.12	-0.37 ± 1.04
Cough, Week 20 (n=75, 130, 114)	-0.29 ± 1.09	-0.24 ± 1.00	-0.51 ± 1.15
Cough, Week 21 (n=69, 129, 113)	-0.36 ± 1.01	-0.26 ± 1.06	-0.46 ± 1.09
Cough, Week 22 (n=79, 125, 109)	-0.25 ± 1.13	-0.27 ± 1.09	-0.44 ± 1.11
Cough, Week 23 (n=70, 128, 106)	-0.26 ± 1.19	-0.30 ± 1.07	-0.45 ± 1.17
Cough, Week 24 (n=67, 121, 105)	-0.28 ± 1.14	-0.33 ± 1.00	-0.46 ± 1.11
Cough, Week 25 (n=48, 118, 104)	-0.28 ± 1.18	-0.31 ± 1.09	-0.52 ± 1.06
Cough, Week 26 (n=48, 111, 99)	-0.41 ± 1.08	-0.32 ± 1.09	-0.54 ± 1.24
Cough, Week 27 (n=42, 110, 95)	-0.27 ± 1.11	-0.39 ± 1.10	-0.31 ± 1.20
Cough, Week 28 (n=41, 103, 88)	-0.34 ± 1.10	-0.36 ± 1.07	-0.52 ± 1.21
Cough, Week 29 (n=38, 100, 89)	-0.38 ± 1.15	-0.33 ± 1.06	-0.48 ± 1.13
Cough, Week 30 (n=46, 104, 86)	-0.29 ± 1.15	-0.31 ± 1.02	-0.54 ± 1.14
Cough, Week 31 (n=35, 97, 77)	-0.46 ± 1.14	-0.34 ± 1.11	-0.49 ± 1.10
Cough, Week 32 (n=29, 91, 70)	-0.17 ± 0.98	-0.41 ± 1.02	-0.53 ± 1.04
Cough, Week 33 (n=29, 93, 68)	-0.31 ± 1.11	-0.35 ± 0.97	-0.53 ± 1.13
Cough, Week 34 (n=33, 92, 73)	-0.03 ± 0.93	-0.34 ± 0.84	-0.41 ± 1.14
Cough, Week 35 (n=33, 90, 72)	-0.14 ± 1.01	-0.38 ± 0.91	-0.47 ± 1.05
Cough, Week 36 (n=31, 83, 64)	-0.05 ± 0.93	-0.39 ± 0.96	-0.43 ± 0.99
Cough, Week 37 (n=24, 84, 65)	-0.08 ± 1.11	-0.22 ± 0.94	-0.54 ± 1.12
Cough, Week 38 (n=24, 86, 65)	0.02 ± 1.09	-0.36 ± 0.97	-0.45 ± 1.16
Cough, Week 39 (n=25, 75, 68)	0.00 ± 1.05	-0.46 ± 1.05	-0.50 ± 1.06
Cough, Week 40 (n=24, 74, 62)	0.10 ± 1.12	-0.39 ± 1.04	-0.47 ± 1.02
Cough, Week 41 (n=22, 69, 60)	0.07 ± 1.21	-0.43 ± 1.10	-0.58 ± 1.06
Cough, Week 42 (n=24, 77, 60)	-0.04 ± 1.16	-0.41 ± 1.05	-0.68 ± 1.05
Cough, Week 43 (n=23, 72, 58)	-0.02 ± 0.87	-0.38 ± 1.04	-0.45 ± 0.99
Cough, Week 44 (n=20, 63, 60)	-0.05 ± 1.24	-0.48 ± 1.21	-0.56 ± 1.09
Cough, Week 45 (n=20, 64, 51)	0.10 ± 1.24	-0.32 ± 1.11	-0.69 ± 1.00
Cough, Week 46 (n=20, 61, 53)	0.03 ± 0.95	-0.38 ± 1.11	-0.67 ± 1.10
Cough, Week 47 (n=20, 64, 48)	0.10 ± 1.15	-0.38 ± 1.13	-0.54 ± 0.97
Cough, Week 48 (n=19, 62, 52)	0.00 ± 1.22	-0.41 ± 1.09	-0.55 ± 1.09
Cough, Week 49 (n=13, 57, 45)	-0.12 ± 1.04	-0.44 ± 1.10	-0.63 ± 1.06
Cough, Week 50 (n=15, 60, 45)	0.23 ± 0.98	-0.29 ± 1.16	-0.72 ± 1.07
Cough, Week 51 (n=11, 58, 37)	0.05 ± 0.88	-0.22 ± 1.20	-0.69 ± 1.11
Cough, Week 52 (n=13, 58, 43)	0.12 ± 0.79	-0.33 ± 1.19	-0.64 ± 1.03
Cough, Week 53 (n=14, 53, 35)	0.21 ± 0.78	-0.28 ± 1.14	-0.53 ± 1.19
Cough, Week 54 (n=13, 56, 36)	0.08 ± 0.89	-0.45 ± 1.06	-0.63 ± 1.23
Cough, Week 55 (n=12, 47, 36)	0.29 ± 1.05	-0.38 ± 1.12	-0.68 ± 1.17
Cough, Week 56 (n=11, 50, 36)	0.14 ± 1.05	-0.46 ± 1.13	-0.51 ± 1.07
Cough, Week 57 (n=10, 52, 33)	0.10 ± 0.81	-0.36 ± 1.25	-0.74 ± 1.10
Cough, Week 58 (n=8, 45, 29)	0.06 ± 0.94	-0.51 ± 1.14	-0.67 ± 1.06
Cough, Week 59 (n=11, 47, 27)	0.18 ± 0.81	-0.45 ± 1.19	-0.81 ± 1.12
Cough, Week 60 (n=11, 41, 31)	0.14 ± 0.71	-0.41 ± 1.26	-0.69 ± 1.04
Cough, Week 61 (n=9, 40, 28)	0.00 ± 0.97	-0.38 ± 1.27	-0.84 ± 1.08
Cough, Week 62 (n=10, 39, 25)	-0.05 ± 0.86	-0.29 ± 1.29	-0.78 ± 1.04
Cough, Week 63 (n=8, 42, 22)	0.19 ± 0.70	-0.30 ± 1.09	-0.82 ± 0.99
Cough, Week 64 (n=8, 42, 18)	0.13 ± 1.16	-0.27 ± 1.21	-0.81 ± 0.93
Cough, Week 65 (n=6, 39, 20)	0.08 ± 0.97	-0.28 ± 1.26	-0.70 ± 1.15
Cough, Week 66 (n=6, 37, 19)	0.08 ± 0.86	-0.30 ± 1.22	-0.82 ± 1.15
Cough, Week 67 (n=5, 33, 20)	-0.30 ± 0.67	-0.44 ± 1.29	-0.78 ± 1.09
Cough, Week 68 (n=6, 33, 19)	0.00 ± 0.95	-0.21 ± 1.36	-0.66 ± 1.17
Cough, Week 69 (n=5, 31, 18)	0.20 ± 0.91	-0.26 ± 1.29	-0.78 ± 1.14
Cough, Week 70 (n=5, 32, 19)	0.20 ± 0.91	-0.28 ± 1.13	-0.92 ± 1.18
Cough, Week 71 (n=6, 27, 15)	-0.17 ± 1.21	-0.15 ± 1.01	-0.90 ± 1.21
Cough, Week 72 (n=9, 27, 18)	0.00 ± 1.38	-0.19 ± 1.10	-0.72 ± 1.05
Cough, Week 73 (n=60, 27, 13)	0.00 ± 1.38	-0.22 ± 1.15	-1.00 ± 1.38
Cough, Week 74 (n=7, 29, 12)	0.07 ± 0.89	-0.22 ± 0.97	-1.04 ± 1.21
Cough, Week 75 (n=6, 24, 12)	0.08 ± 1.24	-0.17 ± 1.12	-1.04 ± 1.29
Cough, Week 76 (n=6, 23, 14)	0.00 ± 1.38	0.07 ± 1.16	-1.18 ± 1.12
Cough, Week 77 (n=6, 22, 10)	0.25 ± 1.29	-0.18 ± 1.29	-0.60 ± 1.05
Cough, Week 78 (n=7, 22, 11)	0.00 ± 1.26	-0.30 ± 1.08	-0.86 ± 1.12
Cough, Week 79 (n=6, 24, 9)	0.00 ± 1.38	-0.04 ± 1.04	-0.61 ± 1.41
Cough, Week 80 (n=7, 20, 11)	0.21 ± 1.07	-0.45 ± 1.17	-0.95 ± 1.13
Cough, Week 81 (n=6, 18, 9)	0.08 ± 1.02	-0.31 ± 1.14	-0.72 ± 1.25
Cough, Week 82 (n=7, 21, 9)	0.43 ± 1.17	-0.33 ± 1.06	-0.44 ± 1.13
Cough, Week 83 (n=5, 19, 10)	0.30 ± 1.44	-0.39 ± 1.06	-1.00 ± 1.20
Cough, Week 84 (n=5, 15, 10)	0.20 ± 1.30	-0.10 ± 1.28	-0.90 ± 1.26
Cough, Week 85 (n=4, 17, 10)	1.00 ± 0.58	-0.24 ± 1.13	-0.60 ± 1.60
Cough, Week 86 (n=3, 15, 6)	1.17 ± 0.58	-0.27 ± 1.28	-0.42 ± 1.32
Cough, Week 87 (n=3, 12, 8)	0.83 ± 0.58	0.00 ± 1.30	-0.94 ± 1.35
Cough, Week 88 (n=3, 15, 7)	0.67 ± 0.76	-0.37 ± 1.19	-1.29 ± 1.41
Cough, Week 89 (n=3, 14, 7)	0.83 ± 0.58	-0.29 ± 1.17	-1.14 ± 1.31
Cough, Week 90 (n=3, 13, 7)	1.00 ± 0.50	-0.35 ± 1.14	-0.79 ± 1.29
Cough, Week 91 (n=3, 13, 7)	0.67 ± 0.76	-0.58 ± 1.19	-0.93 ± 1.37
Cough, Week 92 (n=4, 13, 8)	1.00 ± 0.58	-0.19 ± 1.18	-0.94 ± 1.37
Cough, Week 93 (n=2, 13, 10)	1.00 ± 0.71	-0.42 ± 1.26	-0.90 ± 1.13
Cough, Week 94 (n=3, 11, 8)	0.83 ± 0.58	-0.41 ± 1.26	-0.88 ± 1.25
Cough, Week 95 (n=3, 11, 8)	0.83 ± 0.58	0.00 ± 1.28	-0.81 ± 1.31
Cough, Week 96 (n=3, 11, 8)	0.83 ± 0.58	-0.18 ± 1.45	-1.00 ± 1.31
Cough, Week 97 (n=3, 11, 9)	1.00 ± 0.50	-0.14 ± 1.12	-0.78 ± 1.23
Cough, Week 98 (n=3, 10, 7)	0.50 ± 0.50	-0.35 ± 1.18	-1.00 ± 1.29
Cough, Week 99 (n=3, 10, 7)	0.83 ± 0.58	0.00 ± 1.41	-0.64 ± 1.14
Cough, Week 100 (n=2, 10, 8)	1.00 ± 0.71	-0.35 ± 1.16	-0.81 ± 1.25
Cough, Week 101 (n=3, 10, 7)	0.83 ± 0.58	-0.20 ± 1.32	-0.79 ± 1.32
Cough, Week 102 (n=3, 6, 6)	0.67 ± 0.76	0.00 ± 1.30	-0.75 ± 1.44
Cough, Week 103 (n=2, 9, 6)	0.50 ± 0.00	-0.56 ± 1.07	-0.67 ± 1.44
Cough, Week 104 (n=2, 8, 4)	0.50 ± 0.00	-0.38 ± 1.19	0.00 ± 1.08
Cough, Week 105 (n=2, 6, 6)	0.50 ± 0.00	0.08 ± 0.80	-0.25 ± 1.33
Cough, Week 106 (n=2, 9, 5)	0.50 ± 0.00	-0.28 ± 1.23	-0.80 ± 1.04
Cough, Week 107 (n=2, 7, 4)	0.25 ± 0.35	-0.57 ± 1.48	-1.25 ± 1.19
Cough, Week 108 (n=2, 5, 4)	0.25 ± 0.35	-0.70 ± 1.64	-1.38 ± 1.11
Cough, Week 109 (n=2, 5, 2)	0.50 ± 0.00	-0.30 ± 1.82	-0.75 ± 1.06
Cough, Week 110 (n=2, 3, 4)	0.50 ± 0.00	0.50 ± 1.80	-1.25 ± 1.04
Cough, Week 111 (n=2, 4, 4)	0.75 ± 0.35	-0.13 ± 1.93	-1.25 ± 1.04
Cough, Week 112 (n=2, 3, 2)	0.50 ± 0.00	0.17 ± 1.44	-1.75 ± 0.35
Cough, Week 113 (n=1, 4, 3)	0.50 ± 999999	0.13 ± 1.75	-1.17 ± 1.04
Cough, Week 114 (n=2, 3, 2)	0.25 ± 0.35	0.50 ± 1.80	-1.50 ± 0.71
Cough, Week 115 (n=2, 4, 3)	0.50 ± 0.00	-0.88 ± 1.31	-1.00 ± 1.00
Cough, Week 116 (n=2, 3, 3)	0.75 ± 0.35	-0.50 ± 1.32	-1.33 ± 1.15
Cough, Week 117 (n=2, 2, 2)	0.75 ± 0.35	-0.25 ± 1.77	-1.50 ± 0.71
Cough, Week 118 (n=1, 1, 2)	0.50 ± 0.80	1.00 ± 0.76	-1.50 ± 0.71
Cough, Week 119 (n=0, 1, 2)	0.13 ± 0.75	1.00 ± 0.86	-1.00 ± 0.71
Cough, Week 120 (n=0, 1, 2)	0.06 ± 0.83	1.00 ± 0.81	-1.00 ± 0.71
Cough, Week 121 (n=0, 1, 2)	0.17 ± 0.89	1.00 ± 0.83	-1.00 ± 0.71
Cough, Week 122 (n=0, 1, 2)	0.21 ± 0.89	1.00 ± 0.88	-1.25 ± 0.35
Cough, Week 123 (n=0, 1, 1)	0.17 ± 0.97	1.00 ± 0.83	-2.00 ± 0.88
Cough, Week 124 (n=0, 1, 1)	0.20 ± 0.98	2.00 ± 0.91	-1.00 ± 0.96
Cough, Week 125 (n=0, 0, 1)	0.26 ± 0.95	0.29 ± 0.91	-2.00 ± 0.97
Cough, Week 126 (n=0, 0, 1)	0.23 ± 0.97	0.26 ± 0.85	-1.00 ± 0.98
Cough, Week 127 (n=0, 0, 1)	0.37 ± 0.99	0.34 ± 0.94	-1.00 ± 0.95
Cough, Time of First Pd (n=103, 107, 106)	-0.15 ± 1.05	-0.16 ± 1.12	-0.16 ± 1.05
Cough, Time of Last Tx Dose (n=161, 172, 151)	-0.31 ± 1.10	-0.24 ± 1.09	-0.21 ± 1.13
Cough, Survival FU Month 1 (n=86, 0, 0)	-0.03 ± 1.13	0.32 ± 0.92	0.34 ± 0.94
Cough, Survival FU Month 2 (n=52, 0, 0)	0.03 ± 1.04	0.29 ± 0.92	0.34 ± 0.91
Cough, Survival FU Month 3 (n=40, 0, 0)	-0.18 ± 1.06	0.32 ± 0.92	0.30 ± 0.91
Cough, Survival FU Month 4 (n=32, 0, 0)	-0.09 ± 1.32	0.32 ± 0.93	0.36 ± 0.92
Cough, Survival FU Month 5 (n=26, 0, 0)	-0.04 ± 1.14	0.25 ± 0.90	0.29 ± 0.91
Cough, Survival FU Month 6 (n=23, 0, 0)	-0.17 ± 1.17	0.28 ± 0.93	0.34 ± 0.97
Cough, Survival FU Month 7 (n=3, 0, 0)	1.33 ± 0.29	0.28 ± 0.98	0.44 ± 0.96
Cough, Survival FU Month 8 (n=2, 0, 0)	-0.50 ± 2.12	0.28 ± 0.93	0.24 ± 0.99
Dyspnoea, Week 1 (n=171, 192, 166)	0.18 ± 0.80	0.11 ± 0.76	0.17 ± 0.73
Dyspnoea, Week 2 (n=160, 186, 165)	0.13 ± 0.75	0.11 ± 0.86	0.27 ± 0.88
Dyspnoea, Week 3 (n=165, 175, 165)	0.06 ± 0.83	0.16 ± 0.81	0.30 ± 0.89
Dyspnoea, Week 4 (n=157, 173, 169)	0.17 ± 0.89	0.16 ± 0.83	0.26 ± 0.89
Dyspnoea, Week 5 (n=160, 172, 159)	0.21 ± 0.89	0.25 ± 0.88	0.31 ± 0.85
Dyspnoea, Week 6 (n=151, 170, 161)	0.17 ± 0.97	0.23 ± 0.83	0.29 ± 0.88
Dyspnoea, Week 7 (n=138, 166, 143)	0.20 ± 0.98	0.25 ± 0.91	0.27 ± 0.96
Dyspnoea, Week 8 (n=140, 162, 152)	0.26 ± 0.95	0.29 ± 0.91	0.31 ± 0.97
Dyspnoea, Week 9 (n=135, 162, 143)	0.23 ± 0.97	0.26 ± 0.85	0.33 ± 0.98
Dyspnoea, Week 10 (n=133, 158, 146)	0.37 ± 0.99	0.34 ± 0.94	0.34 ± 0.95
Dyspnoea, Week 11 (n=132, 157, 137)	0.40 ± 0.95	0.31 ± 0.91	0.35 ± 0.97
Dyspnoea, Week 12 (n=128, 151, 136)	0.44 ± 0.98	0.41 ± 1.01	0.29 ± 0.90
Dyspnoea, Week 13 (n=117, 144, 130)	0.40 ± 1.03	0.32 ± 0.92	0.34 ± 0.94
Dyspnoea, Week 14 (n=105, 139, 138)	0.42 ± 0.95	0.29 ± 0.92	0.34 ± 0.91
Dyspnoea, Week 15 (n=97, 143, 132)	0.36 ± 0.98	0.32 ± 0.92	0.30 ± 0.91
Dyspnoea, Week 16 (n=102, 138, 121)	0.45 ± 0.95	0.32 ± 0.93	0.36 ± 0.92
Dyspnoea, Week 17 (n=101, 135, 129)	0.55 ± 0.99	0.25 ± 0.90	0.29 ± 0.91
Dyspnoea, Week 18 (n=93, 141, 129)	0.46 ± 0.93	0.28 ± 0.93	0.34 ± 0.97
Dyspnoea, Week 19 (n=85, 129, 118)	0.48 ± 0.97	0.28 ± 0.98	0.44 ± 0.96
Dyspnoea, Week 20 (n=75, 130, 114)	0.37 ± 0.97	0.28 ± 0.93	0.24 ± 0.99
Dyspnoea, Week 21 (n=69, 129, 113)	0.51 ± 0.94	0.23 ± 0.98	0.19 ± 1.00
Dyspnoea, Week 22 (n=79, 125, 109)	0.50 ± 0.95	0.25 ± 0.96	0.24 ± 1.07
Dyspnoea, Week 23 (n=70, 128, 106)	0.44 ± 0.94	0.30 ± 0.99	0.20 ± 0.98
Dyspnoea, Week 24 (n=67, 121, 105)	0.25 ± 1.01	0.20 ± 0.91	0.29 ± 1.02
Dyspnoea, Week 25 (n=48, 118, 104)	0.27 ± 0.94	0.18 ± 0.95	0.25 ± 1.00
Dyspnoea, Week 26 (n=48, 111, 99)	0.20 ± 0.84	0.31 ± 0.96	0.39 ± 1.02
Dyspnoea, Week 27 (n=42, 110, 95)	0.31 ± 0.80	0.21 ± 0.95	0.36 ± 1.14
Dyspnoea, Week 28 (n=41, 103, 88)	0.24 ± 0.83	0.17 ± 0.86	0.30 ± 1.07
Dyspnoea, Week 29 (n=38, 100, 89)	0.30 ± 0.82	0.19 ± 0.96	0.31 ± 1.07
Dyspnoea, Week 30 (n=46, 104, 86)	0.30 ± 0.82	0.12 ± 0.94	0.39 ± 1.08
Dyspnoea, Week 31 (n=35, 97, 77)	0.34 ± 0.76	0.18 ± 0.96	0.36 ± 1.12
Dyspnoea, Week 32 (n=29, 91, 70)	0.28 ± 0.79	0.09 ± 0.84	0.26 ± 1.05
Dyspnoea, Week 33 (n=29, 93, 68)	0.39 ± 0.74	0.02 ± 0.85	0.31 ± 1.05
Dyspnoea, Week 34 (n=33, 92, 73)	0.32 ± 0.69	0.05 ± 0.76	0.30 ± 1.05
Dyspnoea, Week 35 (n=33, 90, 72)	0.35 ± 0.88	0.04 ± 0.82	0.38 ± 1.05
Dyspnoea, Week 36 (n=31, 83, 64)	0.32 ± 0.68	0.11 ± 0.82	0.37 ± 0.98
Dyspnoea, Week 37 (n=24, 84, 65)	0.24 ± 0.76	0.16 ± 0.92	0.32 ± 0.92
Dyspnoea, Week 38 (n=24, 86, 65)	0.31 ± 0.75	0.10 ± 0.78	0.40 ± 1.01
Dyspnoea, Week 39 (n=25, 75, 68)	0.39 ± 0.76	0.04 ± 0.87	0.36 ± 1.01
Dyspnoea, Week 40 (n=24, 74, 62)	0.38 ± 0.74	0.24 ± 0.92	0.37 ± 0.91
Dyspnoea, Week 41 (n=22, 69, 60)	0.45 ± 0.92	0.13 ± 0.84	0.33 ± 0.89
Dyspnoea, Week 42 (n=24, 77, 60)	0.37 ± 0.82	0.05 ± 0.81	0.29 ± 1.02
Dyspnoea, Week 43 (n=23, 72, 58)	0.48 ± 0.94	0.16 ± 0.76	0.41 ± 1.05
Dyspnoea, Week 44 (n=20, 63, 60)	0.22 ± 0.95	0.11 ± 0.88	0.33 ± 1.08
Dyspnoea, Week 45 (n=20, 64, 51)	0.32 ± 1.04	0.20 ± 0.84	0.27 ± 1.07
Dyspnoea, Week 46 (n=20, 61, 53)	0.36 ± 0.98	0.08 ± 0.78	0.26 ± 0.99
Dyspnoea, Week 47 (n=20, 64, 48)	0.32 ± 0.85	0.06 ± 0.80	0.31 ± 1.01
Dyspnoea, Week 48 (n=19, 62, 52)	0.32 ± 0.88	0.14 ± 0.85	0.22 ± 0.93
Dyspnoea, Week 49 (n=13, 57, 45)	0.46 ± 0.99	0.06 ± 0.78	0.14 ± 0.93
Dyspnoea, Week 50 (n=15, 60, 45)	0.41 ± 0.84	0.10 ± 0.85	0.06 ± 0.86
Dyspnoea, Week 51 (n=11, 58, 37)	0.71 ± 0.92	0.08 ± 0.78	0.15 ± 1.06
Dyspnoea, Week 52 (n=13, 58, 43)	0.60 ± 0.81	0.11 ± 0.86	0.34 ± 0.97
Dyspnoea, Week 53 (n=14, 53, 35)	0.70 ± 0.85	0.11 ± 0.89	0.11 ± 1.11
Dyspnoea, Week 54 (n=13, 56, 36)	0.71 ± 0.94	0.11 ± 0.80	0.10 ± 1.02
Dyspnoea, Week 55 (n=12, 47, 36)	0.82 ± 0.93	0.15 ± 0.85	0.16 ± 1.08
Dyspnoea, Week 56 (n=11, 50, 36)	0.69 ± 0.94	0.14 ± 0.95	0.12 ± 1.02
Dyspnoea, Week 57 (n=10, 52, 33)	0.74 ± 0.80	0.12 ± 0.90	0.13 ± 1.03
Dyspnoea, Week 58 (n=8, 45, 29)	0.80 ± 0.93	0.02 ± 0.98	0.12 ± 1.06
Dyspnoea, Week 59 (n=11, 47, 27)	0.78 ± 1.09	0.11 ± 1.00	-0.03 ± 1.04
Dyspnoea, Week 60 (n=11, 41, 31)	0.67 ± 0.86	0.06 ± 0.93	0.02 ± 1.02
Dyspnoea, Week 61 (n=9, 40, 28)	0.91 ± 0.91	0.05 ± 0.92	-0.18 ± 0.93
Dyspnoea, Week 62 (n=10, 39, 25)	0.58 ± 0.94	0.01 ± 0.96	-0.04 ± 1.01
Dyspnoea, Week 63 (n=8, 42, 22)	0.58 ± 1.14	0.10 ± 0.95	-0.06 ± 0.72
Dyspnoea, Week 64 (n=8, 42, 18)	0.63 ± 0.98	0.07 ± 1.08	-0.22 ± 0.74
Dyspnoea, Week 65 (n=6, 39, 20)	0.80 ± 1.06	0.05 ± 1.05	-0.18 ± 0.87
Dyspnoea, Week 66 (n=6, 37, 19)	0.70 ± 1.02	0.04 ± 1.07	-0.18 ± 0.85
Dyspnoea, Week 67 (n=5, 33, 20)	0.52 ± 0.95	0.04 ± 1.15	-0.24 ± 0.97
Dyspnoea, Week 68 (n=6, 33, 19)	0.63 ± 0.98	0.01 ± 1.07	-0.11 ± 0.86
Dyspnoea, Week 69 (n=5, 31, 18)	0.96 ± 0.59	0.06 ± 1.19	-0.20 ± 0.87
Dyspnoea, Week 70 (n=5, 32, 19)	1.00 ± 0.60	0.16 ± 1.08	-0.18 ± 0.94
Dyspnoea, Week 71 (n=6, 27, 15)	0.70 ± 0.91	0.22 ± 1.08	-0.01 ± 0.82
Dyspnoea, Week 72 (n=6, 27, 18)	0.57 ± 0.98	0.25 ± 1.16	-0.06 ± 0.79
Dyspnoea, Week 73 (n=6, 27, 13)	0.67 ± 1.07	0.10 ± 1.18	-0.11 ± 0.79
Dyspnoea, Week 74 (n=7, 29, 12)	0.74 ± 0.96	0.10 ± 1.15	-0.17 ± 0.86
Dyspnoea, Week 75 (n=6, 24, 12)	0.70 ± 0.99	0.05 ± 1.13	-0.22 ± 0.81
Dyspnoea, Week 76 (n=6, 23, 14)	0.67 ± 0.90	0.25 ± 1.33	-0.13 ± 0.90
Dyspnoea, Week 77 (n=6, 22, 10)	0.73 ± 0.95	0.04 ± 1.36	0.12 ± 0.76
Dyspnoea, Week 78 (n=7, 22, 11)	0.57 ± 0.94	0.09 ± 1.24	-0.20 ± 0.95
Dyspnoea, Week 79 (n=6, 24, 9)	0.57 ± 0.77	0.16 ± 1.29	-0.13 ± 0.93
Dyspnoea, Week 80 (n=7, 20, 11)	0.60 ± 0.78	-0.13 ± 1.17	0.00 ± 0.81
Dyspnoea, Week 81 (n=6, 18, 9)	0.50 ± 0.92	-0.02 ± 1.17	-0.04 ± 0.86
Dyspnoea, Week 82 (n=7, 21, 9)	0.57 ± 0.91	-0.05 ± 1.16	0.00 ± 0.90
Dyspnoea, Week 83 (n=5, 19, 10)	0.28 ± 0.69	-0.08 ± 1.26	-0.40 ± 0.98
Dyspnoea, Week 84 (n=5, 15, 10)	0.16 ± 0.59	-0.17 ± 1.23	-0.22 ± 0.99
Dyspnoea, Week 85 (n=4, 17, 10)	0.70 ± 0.50	-0.16 ± 1.11	-0.16 ± 1.03
Dyspnoea, Week 86 (n=3, 15, 6)	1.33 ± 1.45	-0.23 ± 1.12	-0.17 ± 1.26
Dyspnoea, Week 87 (n=3, 12, 8)	0.40 ± 0.40	0.08 ± 1.45	-0.25 ± 1.06
Dyspnoea, Week 88 (n=3, 15, 7)	0.40 ± 0.69	-0.21 ± 1.06	-0.51 ± 1.06
Dyspnoea, Week 89 (n=3, 14, 7)	0.53 ± 0.42	-0.13 ± 1.02	-0.06 ± 1.12
Dyspnoea, Week 90 (n=3, 13, 7)	0.27 ± 0.31	-0.32 ± 0.99	-0.17 ± 1.07
Dyspnoea, Week 91 (n=3, 13, 7)	0.33 ± 0.31	-0.52 ± 0.81	-0.17 ± 1.13
Dyspnoea, Week 92 (n=4, 13, 8)	0.75 ± 0.66	-0.28 ± 1.02	-0.10 ± 1.06
Dyspnoea, Week 93(n=2, 13, 10)	0.40 ± 0.28	-0.23 ± 0.93	-0.14 ± 0.90
Dyspnoea, Week 94 (n=3, 11, 8)	0.67 ± 0.70	-0.38 ± 0.85	-0.25 ± 0.98
Dyspnoea, Week 95 (n=3, 11, 8)	0.53 ± 0.23	-0.07 ± 1.21	-0.20 ± 1.04
Dyspnoea, Week 96 (n=3, 11, 8)	0.33 ± 0.42	-0.02 ± 1.21	-0.18 ± 1.09
Dyspnoea, Week 97 (n=3, 11, 9)	0.67 ± 0.42	-0.22 ± 1.18	0.04 ± 1.13
Dyspnoea, Week 98 (n=3, 10, 7)	0.73 ± 0.50	-0.18 ± 1.19	-0.29 ± 1.08
Dyspnoea, Week 99 (n=3, 10, 7)	0.47 ± 0.46	-0.26 ± 1.25	-0.29 ± 1.09
Dyspnoea, Week 100 (n=2, 10, 8)	0.50 ± 0.42	-0.24 ± 1.24	-0.20 ± 1.08
Dyspnoea, Week 101 (n=3, 10, 7)	0.40 ± 0.35	-0.26 ± 1.23	-0.03 ± 1.09
Dyspnoea, Week 102 (n=3, 6, 9)	0.40 ± 0.35	-0.67 ± 0.89	0.00 ± 1.08
Dyspnoea, Week 103 (n=2, 9, 6)	0.70 ± 0.42	-0.60 ± 0.73	-0.03 ± 1.24
Dyspnoea, Week 104 (n=2, 8, 4)	0.50 ± 0.71	-0.63 ± 0.82	-0.35 ± 1.42
Dyspnoea, Week 105 (n=2, 6, 6)	0.40 ± 0.57	-0.20 ± 0.33	0.23 ± 0.92
Dyspnoea, Week 106 (n=2, 9, 5)	0.30 ± 0.42	-0.24 ± 0.31	-0.04 ± 0.57
Dyspnoea, Week 107(n=2, 7, 4)	0.60 ± 0.28	-0.17 ± 0.35	-0.30 ± 0.74
Dyspnoea, Week 108 (n=2, 5, 4)	0.60 ± 0.28	-0.36 ± 0.43	-0.40 ± 0.88
Dyspnoea, Week 109(n=2, 5, 2)	0.80 ± 0.00	-0.40 ± 0.47	0.10 ± 0.99
Dyspnoea, Week 110(n=2, 3, 4)	0.60 ± 0.28	-0.27 ± 0.50	-0.40 ± 0.94
Dyspnoea, Week 111 (n=2, 4, 4)	0.30 ± 0.42	-0.15 ± 0.34	-0.45 ± 0.91
Dyspnoea, Week 112 (n=2, 3, 2)	0.50 ± 0.42	-0.20 ± 0.40	-1.30 ± 0.14
Dyspnoea, Week 113(n=1, 4, 3)	1.00 ± 999999	-0.35 ± 0.44	-0.47 ± 1.14
Dyspnoea, Week 114(n=2, 3, 2)	0.50 ± 0.71	-0.27 ± 0.50	-1.30 ± 0.14
Dyspnoea, Week 115(n=2, 4, 3)	0.50 ± 0.71	-0.40 ± 0.28	-0.67 ± 1.10
Dyspnoea, Week 116(n=2, 3, 3)	0.40 ± 0.57	-0.20 ± 0.53	-0.73 ± 1.17
Dyspnoea, Week 117(n=2, 2, 2)	0.40 ± 0.28	-0.60 ± 0.28	-1.20 ± 0.28
Dyspnoea, Week 118 (n=1, 1, 2)	1.00 ± 999999	-0.80 ± 999999	-1.20 ± 0.57
Dyspnoea, Week 119(n=0, 1, 2)	999999 ± 999999	-0.80 ± 999999	-1.40 ± 0.28
Dyspnoea, Week 120 (n=0, 1, 2)	999999 ± 999999	-0.80 ± 999999	-1.10 ± 0.42
Dyspnoea, Week 121 (n=0, 1, 2)	999999 ± 999999	-0.80 ± 999999	-1.30 ± 0.14
Dyspnoea, Week 122(n=0, 1, 2)	999999 ± 999999	-0.80 ± 999999	-1.30 ± 0.14
Dyspnoea, Week 123(n=0, 1, 1)	999999 ± 999999	-0.80 ± 999999	-1.00 ± 999999
Dyspnoea, Week 124 (n=0, 1, 1)	999999 ± 999999	-0.80 ± 999999	-1.20 ± 999999
Dyspnoea, Week 125 (n=0, 0, 1)	999999 ± 999999	999999 ± 999999	-1.00 ± 999999
Dyspnoea, Week 126 (n=0, 0, 1)	999999 ± 999999	999999 ± 999999	-1.20 ± 999999
Dyspnoea, Week 127(n=0, 0, 1)	999999 ± 999999	999999 ± 999999	-1.20 ± 999999
Dyspnoea, Time of First Pd (n=103, 107, 106)	0.38 ± 1.06	0.42 ± 0.95	0.27 ± 1.13
Dyspnoea, Time of Last Tx Dose (n=161, 172, 151)	0.43 ± 0.91	0.28 ± 1.01	0.28 ± 1.00
Dyspnoea, Survival FU Month 1 (n=86, 0, 0)	0.56 ± 1.09	999999 ± 999999	999999 ± 999999
Dyspnoea, Survival FU Month 2 (n=52, 0, 0)	0.71 ± 0.89	999999 ± 999999	999999 ± 999999
Dyspnoea, Survival FU Month 3 (n=40, 0, 0)	0.67 ± 1.06	999999 ± 999999	999999 ± 999999
Dyspnoea, Survival FU Month 4 (n=32, 0, 0)	0.57 ± 0.91	999999 ± 999999	999999 ± 999999
Dyspnoea, Survival FU Month 5 (n=29, 0, 0)	0.66 ± 1.02	999999 ± 999999	999999 ± 999999
Dyspnoea, Survival FU Month 6 (n=23, 0, 0)	0.63 ± 1.09	999999 ± 999999	999999 ± 999999
Dyspnoea, Survival FU Month 7 (n=3, 0, 0)	1.07 ± 1.36	999999 ± 999999	999999 ± 999999
Dyspnoea, Survival FU Month 8 (n=2, 0, 0)	0.10 ± 0.14	999999 ± 999999	999999 ± 999999

No statistical analyses for this end point

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A and Arm B)

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End point title

PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A and Arm B) ^[17]

End point description

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT Population Arm A and Arm B.

End point type

Secondary

End point timeframe

Up to approximately 30 months after first participant enrolled

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	343	338
Units: Months
median (confidence interval 95%)	6.5 (5.7 to 7.1)	5.6 (5.5 to 6.9)

PFS in ITT

Comparison groups

Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

681

Analysis specification

Pre-specified

Analysis type

^[18]

P-value

= 0.4007

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.93

Confidence interval

level

95%

sides

2-sided

lower limit

0.784

upper limit

1.102

Notes
[18] - Stratified Analysis

Secondary: OS in the ITT Population (Arm A and Arm B)

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End point title

OS in the ITT Population (Arm A and Arm B) ^[19]

End point description

OS is defined as the time between the date of randomization and date of death from any cause in the ITT Population, Arm A and Arm B.

End point type

Secondary

End point timeframe

Up to approximately 39 months after first participant enrolled

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	343	338
Units: Months
median (confidence interval 95%)	14.2 (12.3 to 16.8)	12.6 (11.6 to 14.7)

No statistical analyses for this end point

Secondary: Percentage of Participants With Adverse Events

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End point title

Percentage of Participants With Adverse Events

End point description

Percentage of participants with at least one adverse event.

End point type

Secondary

End point timeframe

Up to approximately 68 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	334	334	332
Units: Percentage of participants
number (not applicable)	28.7	50.3	45.5

No statistical analyses for this end point

Secondary: Percentage of Participants with Anti-therapeutic Antibody (ATA) Response to Atezolizumab

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End point title

Percentage of Participants with Anti-therapeutic Antibody (ATA) Response to Atezolizumab ^[20]

End point description

Percentage of participants with Anti-therapeutic Antibody (ATA) response to atezolizumab.

End point type

Secondary

End point timeframe

Up to approximately 30 months after first participant enrolled

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	343	338
Units: Percentage of participants
number (not applicable)
Baseline evaluable participants	1.9	3.1
Post-baseline evaluable participants	21.4	48.1

No statistical analyses for this end point

Secondary: Maximum Observed Serum Atezolizumab Concentration (Cmax)

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End point title

Maximum Observed Serum Atezolizumab Concentration (Cmax) ^[21]

End point description

Maximum observed serum atezolizumab concentration (Cmax). The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.

End point type

Secondary

End point timeframe

Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length = 21 days)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	328	327
Units: µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 Post dose	378 ± 124	372 ± 116
Cycle 3 Day 1 Post dose	444 ± 119	470 ± 147

No statistical analyses for this end point

Secondary: Minimum Observed Serum Atezolizumab Concentration (Cmin)

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End point title

Minimum Observed Serum Atezolizumab Concentration (Cmin) ^[22]

End point description

Minimum observed serum atezolizumab concentration (Cmin). The predose samples will be collected on the same day of treatment administration. (Note: 888888=Non-reportable. 777777=Not evaluable.)

End point type

Secondary

End point timeframe

Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle thereafter (up to 30 months), at treatment discontinuation (up to 30 months), and at 120 days after the last dose of atezolizumab (up to approximately 30 months, each cycle is 21 days)

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	328	327
Units: µg/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1	888888 ± 888888	888888 ± 888888
Cycle 2 Day 1	69.5 ± 34.7	63.9 ± 29.9
Cycle 3 Day 1	107 ± 52.0	103 ± 40.1
Cycle 4 Day 1	126 ± 68.4	128 ± 62.3
Cycle 8 Day 1	190 ± 84.6	188 ± 80.4
Cycle 16 Day 1	212 ± 78.1	201 ± 79.2
Cycle 24 Day 1	224 ± 134	187 ± 90.4
Cycle 32 Day 1	210 ± 102	242 ± 88.4
Cycle 40 Day 1	174 ± 777777	308 ± 141
Treatment Discontinuation Visit	137 ± 103	126 ± 93.7
Day 120 Post Last Dose	9.47 ± 13.1	7.81 ± 9.76

No statistical analyses for this end point

Secondary: Plasma Concentrations for Paclitaxel

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End point title

Plasma Concentrations for Paclitaxel ^[23]

End point description

Plasma concentrations for paclitaxel. (Note: 888888=Non-reportable.)

End point type

Secondary

End point timeframe

Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 180 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)

Notes
[23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	35
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 Prior to Infusion	888888 ± 888888
Cycle 1 Day 1 Before end of Infusion	5860 ± 2410
Cycle 1 Day 1 After Infusion	2960 ± 2770
Cycle 3 Day 1 Prior to Infusion	888888 ± 888888
Cycle 3 Day 1 Before end of Infusion	21900 ± 42600
Cycle 3 Day 1 After Infusion	11000 ± 30700

No statistical analyses for this end point

Secondary: Plasma Concentrations for Nab-Paclitaxel

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End point title

Plasma Concentrations for Nab-Paclitaxel ^[24]

End point description

Plasma concentrations for nab-paclitaxel. (Note: 888888=Non-reportable.)

End point type

Secondary

End point timeframe

Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis for this endpoint.

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
Number of subjects analysed	38	32
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 Prior to Infusion	888888 ± 888888	888888 ± 888888
Cycle 1 Day 1 Before End of Infusion	8160 ± 20900	3330 ± 3680
Cycle 1 Day 1 After Infusion	921 ± 2080	735 ± 1300
Cycle 3 Day 1 Prior to Infusion	888888 ± 888888	888888 ± 888888
Cycle 3 Day 1 Before End of Infusion	7180 ± 14400	7160 ± 12300
Cycle 3 Day 1 After Infusion	1140 ± 2070	296 ± 274

No statistical analyses for this end point

Secondary: Plasma Concentrations for Carboplatin

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End point title

Plasma Concentrations for Carboplatin

End point description

Plasma concentrations for carboplatin. (Note: 888888=Non-reportable.)

End point type

Secondary

End point timeframe

Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 15 to 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	39	33	34
Units: ng/mL
arithmetic mean (standard deviation)
Cycle 1 Day 1 Prior to Infusion	888888 ± 888888	888888 ± 888888	888888 ± 888888
Cycle 1 Day 1 Before End of Infusion	24900 ± 38200	15900 ± 9270	21100 ± 12400
Cycle 1 Day 1 After Infusion	10800 ± 6230	9890 ± 4780	11900 ± 6410
Cycle 3 Day 1 Prior to Infusion	161 ± 70.0	147 ± 60.9	238 ± 276
Cycle 3 Day 1 Before End of Infusion	26800 ± 31900	23500 ± 21600	33800 ± 38600
Cycle 3 Day 1 After Infusion	14700 ± 14600	11200 ± 5160	20000 ± 30900

No statistical analyses for this end point

Secondary: OS in the in the Teff Population

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End point title

OS in the in the Teff Population

End point description

OS is defined as the time between the date of randomization and date of death from any cause in the in the Teff Population.

End point type

Secondary

End point timeframe

Up to approximately 39 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	322	313	308
Units: Month
median (confidence interval 95%)
Teff >=-1.91 (n=147, 124, 123)	16.4 (12.2 to 19.7)	17.4 (12.3 to 23.8)	15.2 (13.4 to 22.8)
Teff<-1.91 (n=175, 189, 185)	12.4 (11.2 to 14.3)	13.0 (11.4 to 14.8)	10.5 (9.1 to 12.6)

OS Teff >=-1.91 in ITT Population

Statistical analysis description

Teff >=-1.91 in ITT

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

635

Analysis specification

Pre-specified

Analysis type

^[25]

P-value

= 0.4451

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.876

Confidence interval

level

95%

sides

2-sided

lower limit

0.623

upper limit

1.231

Notes
[25] - Stratified Analysis

OS Teff >=-1.91 in ITT Population

Statistical analysis description

Teff >=-1.91 in ITT

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

630

Analysis specification

Pre-specified

Analysis type

^[26]

P-value

= 0.7343

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.941

Confidence interval

level

95%

sides

2-sided

lower limit

0.664

upper limit

1.335

Notes
[26] - Stratified Analysis

OS Teff <-1.91 Negative in ITT Population

Statistical analysis description

Teff <-1.91 Negative in ITT

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

635

Analysis specification

Pre-specified

Analysis type

^[27]

P-value

= 0.661

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.942

Confidence interval

level

95%

sides

2-sided

lower limit

0.72

upper limit

1.232

Notes
[27] - Stratified Analysis

OS Teff <-1.91 Negative in ITT Population

Statistical analysis description

Teff <-1.91 Negative in ITT

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

630

Analysis specification

Pre-specified

Analysis type

^[28]

P-value

= 0.0893

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.253

Confidence interval

level

95%

sides

2-sided

lower limit

0.965

upper limit

1.627

Notes
[28] - Stratified Analysis

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population

Top of page

End point title

PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population

End point description

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the Teff Population.

End point type

Secondary

End point timeframe

Up to approximately 30 months after first participant enrolled

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	322	313	308
Units: Months
median (confidence interval 95%)
Teff >=-1.91 (n=147, 124, 123)	5.6 (5.1 to 5.7)	7.0 (5.5 to 8.5)	7.0 (5.6 to 9.7)
Teff<-1.91 (n=175, 189, 185)	5.7 (5.5 to 6.6)	6.2 (5.6 to 7.0)	5.5 (4.5 to 5.6)

PFS in Teff>=-1.91 Population

Statistical analysis description

Teff>=-1.91

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

635

Analysis specification

Pre-specified

Analysis type

^[29]

P-value

= 0.0006

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.46

upper limit

0.81

Notes
[29] - Stratified Analysis

PFS in Teff>=-1.91 Population

Statistical analysis description

Teff>=-1.91

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

630

Analysis specification

Pre-specified

Analysis type

^[30]

P-value

= 0.63

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.33

Notes
[30] - Stratified Analysis

PFS in Teff<-1.91 Population

Statistical analysis description

Teff<-1.91

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

635

Analysis specification

Pre-specified

Analysis type

^[31]

P-value

= 0.258

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.88

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

1.1

Notes
[31] - Stratified Analysis

PFS in Teff<-1.91 Population

Statistical analysis description

Teff<-1.91

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

630

Analysis specification

Pre-specified

Analysis type

^[32]

P-value

= 0.63

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.84

upper limit

1.33

Notes
[32] - Stratified Analysis

Secondary: Event Free Rate at 1 and 2 Years in the ITT Population

Top of page

End point title

Event Free Rate at 1 and 2 Years in the ITT Population

End point description

Event free rate at 1 and 2 years is defined as the proportion of participants alive at 1 and 2 years after randomization estimated using Kaplan-Meier (KM) methodology for the ITT population.

End point type

Secondary

End point timeframe

1 and 2 years

End point values	Arm C: Nab-Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin
Number of subjects analysed	184	187	170
Units: Percentage of participants
number (not applicable)
1 Year (n=184, 187, 170)	56.28	56.34	52.30
2 Year (n=49, 68, 50)	26.58	32.51	27.79

Event Free Rate in ITT Population

Statistical analysis description

Event Free Rate (%) at Year 1

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

371

Analysis specification

Pre-specified

Analysis type

P-value

= 0.9871

Method

Z-test

Parameter type

Difference in Event Free Rate

Point estimate

0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-7.48

upper limit

7.61

Event Free Rate in ITT Population

Statistical analysis description

Event Free Rate (%) at Year 2

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Number of subjects included in analysis

371

Analysis specification

Pre-specified

Analysis type

P-value

= 0.1133

Method

Z-test

Parameter type

Difference in Event Free Rate

Point estimate

5.93

Confidence interval

level

95%

sides

2-sided

lower limit

-1.41

upper limit

13.26

Event Free Rate in ITT Population

Statistical analysis description

Event Free Rate (%) at Year 1

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

354

Analysis specification

Pre-specified

Analysis type

P-value

= 0.3072

Method

Z-test

Parameter type

Difference in Event Free Rate

Point estimate

-3.97

Confidence interval

level

95%

sides

2-sided

lower limit

-11.6

upper limit

3.65

Event Free Rate in ITT Population

Statistical analysis description

Event Free Rate (%) at Year 2

Comparison groups

Arm C: Nab-Paclitaxel + Carboplatin v Arm A: Atezolizumab + Paclitaxel + Carboplatin

Number of subjects included in analysis

354

Analysis specification

Pre-specified

Analysis type

P-value

= 0.743

Method

Z-test

Parameter type

Difference in Event Free Rate

Point estimate

1.21

Confidence interval

level

95%

sides

2-sided

lower limit

-6.01

upper limit

8.42

Adverse events

Top of page

Timeframe for reporting adverse events

From the first study drug administration to the data cutoff date: 17 February 2021 (up to approximately 68 months).

Adverse event reporting additional description

Safety-evaluable population included all participants who received at least one dose of any study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Arm C: Nab-Paclitaxel + Carboplatin

Reporting group description

Reporting group title

Arm A: Atezolizumab + Paclitaxel + Carboplatin

Reporting group description

Reporting group title

Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin

Reporting group description

Serious adverse events	Arm C: Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
Total subjects affected by serious adverse events
subjects affected / exposed	96 / 334 (28.74%)	151 / 332 (45.48%)	168 / 334 (50.30%)
number of deaths (all causes)	265	248	244
number of deaths resulting from adverse events	3	9	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA OF COLON
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PROSTATE CANCER
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TUMOUR EMBOLISM
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
BENIGN SALIVARY GLAND NEOPLASM
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFECTED NEOPLASM
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
BLADDER CANCER
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COLON CANCER
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GALLBLADDER ADENOCARCINOMA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MYELODYSPLASTIC SYNDROME
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
Vascular disorders
EMBOLISM
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
DEEP VEIN THROMBOSIS
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PERIPHERAL ISCHAEMIA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ARTERITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
THROMBOSIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOTENSION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMODYNAMIC INSTABILITY
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ORTHOSTATIC HYPOTENSION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ARTERIAL STENOSIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SUPERIOR VENA CAVA SYNDROME
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Surgical and medical procedures
TRANSURETHRAL PROSTATECTOMY
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
THERAPEUTIC EMBOLISATION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
OEDEMA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NON-CARDIAC CHEST PAIN
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PYREXIA
subjects affected / exposed	5 / 334 (1.50%)	6 / 332 (1.81%)	6 / 334 (1.80%)
occurrences causally related to treatment / all	3 / 6	3 / 8	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PAIN
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FATIGUE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	0 / 0	1 / 1	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ASTHENIA
subjects affected / exposed	1 / 334 (0.30%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CHEST PAIN
subjects affected / exposed	2 / 334 (0.60%)	3 / 332 (0.90%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PERFORMANCE STATUS DECREASED
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MUCOSAL INFLAMMATION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DEATH
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	8 / 334 (2.40%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 8
deaths causally related to treatment / all	0 / 0	1 / 2	0 / 8
MALAISE
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GAIT DISTURBANCE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Immune system disorders
HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DRUG HYPERSENSITIVITY
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ANAPHYLACTIC REACTION
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
PROSTATITIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
DIAPHRAGMATIC PARALYSIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DYSPNOEA
subjects affected / exposed	3 / 334 (0.90%)	8 / 332 (2.41%)	7 / 334 (2.10%)
occurrences causally related to treatment / all	0 / 4	0 / 8	1 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
DYSPNOEA AT REST
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LUNG DISORDER
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOXIA
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INTERSTITIAL LUNG DISEASE
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
IMMUNE-MEDIATED PNEUMONITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PLEURAL EFFUSION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
EMPHYSEMA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
EPISTAXIS
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	1 / 1	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LUNG CONSOLIDATION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA ASPIRATION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONITIS
subjects affected / exposed	2 / 334 (0.60%)	10 / 332 (3.01%)	10 / 334 (2.99%)
occurrences causally related to treatment / all	2 / 2	10 / 10	10 / 10
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
PARANASAL CYST
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COUGH
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BRONCHIAL HAEMORRHAGE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DYSPNOEA EXERTIONAL
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PULMONARY OEDEMA
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HAEMOPTYSIS
subjects affected / exposed	2 / 334 (0.60%)	6 / 332 (1.81%)	5 / 334 (1.50%)
occurrences causally related to treatment / all	0 / 2	1 / 8	0 / 5
deaths causally related to treatment / all	0 / 0	1 / 3	0 / 1
ASPIRATION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1
ATELECTASIS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMOTHORAX
subjects affected / exposed	3 / 334 (0.90%)	2 / 332 (0.60%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PULMONARY EMBOLISM
subjects affected / exposed	3 / 334 (0.90%)	7 / 332 (2.11%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	0 / 3	0 / 7	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 4	0 / 0
PNEUMOTHORAX SPONTANEOUS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LARYNGEAL HAEMORRHAGE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	3 / 334 (0.90%)	10 / 332 (3.01%)	7 / 334 (2.10%)
occurrences causally related to treatment / all	0 / 3	1 / 14	0 / 9
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 3
ACUTE RESPIRATORY FAILURE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RESPIRATORY FAILURE
subjects affected / exposed	3 / 334 (0.90%)	3 / 332 (0.90%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 3	2 / 4	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0
Psychiatric disorders
DEPRESSION
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HALLUCINATION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CONFUSIONAL STATE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COMPLETED SUICIDE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2
SUICIDAL IDEATION
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MENTAL STATUS CHANGES
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Product issues
DEVICE DISLOCATION
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
PLATELET COUNT DECREASED
subjects affected / exposed	2 / 334 (0.60%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	1 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEUTROPHIL COUNT DECREASED
subjects affected / exposed	1 / 334 (0.30%)	3 / 332 (0.90%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	1 / 1	3 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BLOOD CREATININE INCREASED
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LIVER FUNCTION TEST ABNORMAL
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BLOOD LACTIC ACID INCREASED
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GENERAL PHYSICAL CONDITION ABNORMAL
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
WEIGHT DECREASED
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
CHEST INJURY
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SUBDURAL HAEMATOMA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RADIATION OESOPHAGITIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RADIATION PNEUMONITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFUSION RELATED REACTION
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PERIORBITAL HAEMATOMA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEMORAL NECK FRACTURE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEMUR FRACTURE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HIP FRACTURE
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
THORACIC VERTEBRAL FRACTURE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TOXICITY TO VARIOUS AGENTS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HUMERUS FRACTURE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RIB FRACTURE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SKIN LACERATION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ALCOHOL POISONING
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FALL
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
TRACHEO-OESOPHAGEAL FISTULA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
SINUS TACHYCARDIA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ANGINA UNSTABLE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TACHYCARDIA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PERICARDIAL EFFUSION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	4 / 334 (1.20%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BRADYCARDIA
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ARRHYTHMIA
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ATRIAL THROMBOSIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ATRIAL FLUTTER
subjects affected / exposed	1 / 334 (0.30%)	5 / 332 (1.51%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	1 / 1	3 / 5	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0
CARDIAC FAILURE ACUTE
subjects affected / exposed	2 / 334 (0.60%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 2	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 2	1 / 1	0 / 0
ACUTE MYOCARDIAL INFARCTION
subjects affected / exposed	1 / 334 (0.30%)	2 / 332 (0.60%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
CARDIO-RESPIRATORY ARREST
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
CORONARY ARTERY STENOSIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CARDIAC ARREST
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 2	0 / 0
ATRIAL FIBRILLATION
subjects affected / exposed	3 / 334 (0.90%)	6 / 332 (1.81%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 3	2 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LEFT VENTRICULAR DYSFUNCTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CARDIAC TAMPONADE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MYOCARDIAL INFARCTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
CARDIAC FAILURE
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Nervous system disorders
BRAIN OEDEMA
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SPINAL CORD COMPRESSION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEMIPLEGIA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CEREBRAL ISCHAEMIA
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TRANSIENT ISCHAEMIC ATTACK
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DEPRESSED LEVEL OF CONSCIOUSNESS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SYNCOPE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PARAESTHESIA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GUILLAIN-BARRE SYNDROME
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
DIZZINESS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MOTOR DYSFUNCTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOTONIA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MYXOEDEMA COMA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SEIZURE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
EMBOLIC STROKE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
EPILEPSY
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERAESTHESIA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ISCHAEMIC STROKE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CEREBROVASCULAR ACCIDENT
subjects affected / exposed	1 / 334 (0.30%)	4 / 332 (1.20%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0
Blood and lymphatic system disorders
HAEMOLYSIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NEUTROPENIA
subjects affected / exposed	3 / 334 (0.90%)	2 / 332 (0.60%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	2 / 3	2 / 2	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ANAEMIA
subjects affected / exposed	3 / 334 (0.90%)	6 / 332 (1.81%)	7 / 334 (2.10%)
occurrences causally related to treatment / all	2 / 3	5 / 6	6 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FEBRILE NEUTROPENIA
subjects affected / exposed	5 / 334 (1.50%)	16 / 332 (4.82%)	13 / 334 (3.89%)
occurrences causally related to treatment / all	5 / 5	15 / 16	15 / 15
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
THROMBOCYTOPENIA
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	1 / 1	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PANCYTOPENIA
subjects affected / exposed	2 / 334 (0.60%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
RETINAL DETACHMENT
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
GASTROINTESTINAL TOXICITY
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CONSTIPATION
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VOMITING
subjects affected / exposed	1 / 334 (0.30%)	3 / 332 (0.90%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 1	2 / 3	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTRITIS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RECTAL HAEMORRHAGE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ANAL HAEMORRHAGE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
UPPER GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INTESTINAL PERFORATION
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COLITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	0 / 0	1 / 1	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIARRHOEA
subjects affected / exposed	4 / 334 (1.20%)	3 / 332 (0.90%)	6 / 334 (1.80%)
occurrences causally related to treatment / all	4 / 5	4 / 4	4 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PANCREATITIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DUODENAL PERFORATION
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL HAEMORRHAGE
subjects affected / exposed	2 / 334 (0.60%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1
OESOPHAGITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DYSPHAGIA
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL PERFORATION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTRIC ULCER
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ABDOMINAL PAIN UPPER
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PANCREATITIS CHRONIC
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ENTEROCOLITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0
INGUINAL HERNIA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
GASTROINTESTINAL NECROSIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SMALL INTESTINAL OBSTRUCTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
NAUSEA
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	1 / 1	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ABDOMINAL PAIN
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 1	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LARGE INTESTINE PERFORATION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1
IMMUNE-MEDIATED HEPATITIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BILE DUCT STONE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DRUG-INDUCED LIVER INJURY
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CHOLECYSTITIS ACUTE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEPATITIS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEPATITIS TOXIC
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
AUTOIMMUNE HEPATITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CHOLECYSTITIS
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	1 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
ERYTHEMA MULTIFORME
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RASH
subjects affected / exposed	0 / 334 (0.00%)	2 / 332 (0.60%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	1 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DERMATITIS ACNEIFORM
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
ACUTE KIDNEY INJURY
subjects affected / exposed	1 / 334 (0.30%)	2 / 332 (0.60%)	4 / 334 (1.20%)
occurrences causally related to treatment / all	0 / 1	2 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYDRONEPHROSIS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINARY RETENTION
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 1	1 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
HYPOPITUITARISM
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ADRENAL INSUFFICIENCY
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERTHYROIDISM
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
FLANK PAIN
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PATHOLOGICAL FRACTURE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
POLYMYOSITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
POLYARTHRITIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MUSCULOSKELETAL CHEST PAIN
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BACK PAIN
subjects affected / exposed	0 / 334 (0.00%)	5 / 332 (1.51%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OSTEONECROSIS OF JAW
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OSTEONECROSIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ARTHRALGIA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
ABDOMINAL SEPSIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BRONCHITIS
subjects affected / exposed	1 / 334 (0.30%)	6 / 332 (1.81%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	0 / 1	2 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PSEUDOMONAL SEPSIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LUNG ABSCESS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ABDOMINAL INFECTION
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COLONIC ABSCESS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFLUENZA
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
GASTROENTERITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA STAPHYLOCOCCAL
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA HAEMOPHILUS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HEPATITIS B
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
MENINGITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
OSTEOMYELITIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
BACTERAEMIA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
STOMATOCOCCAL INFECTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
APPENDICITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA STREPTOCOCCAL
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFECTION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PULMONARY SEPSIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
VASCULAR DEVICE INFECTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	3 / 334 (0.90%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PLEURAL INFECTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CLOSTRIDIUM DIFFICILE INFECTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
ENTEROCOLITIS INFECTIOUS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SINUSITIS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION STAPHYLOCOCCAL
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA BACTERIAL
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
UROSEPSIS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SEPSIS
subjects affected / exposed	6 / 334 (1.80%)	10 / 332 (3.01%)	5 / 334 (1.50%)
occurrences causally related to treatment / all	2 / 6	2 / 11	1 / 5
deaths causally related to treatment / all	0 / 2	1 / 3	0 / 2
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	21 / 334 (6.29%)	30 / 332 (9.04%)	33 / 334 (9.88%)
occurrences causally related to treatment / all	9 / 21	7 / 32	6 / 37
deaths causally related to treatment / all	1 / 1	2 / 4	2 / 6
INFECTED DERMAL CYST
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
RESPIRATORY TRACT INFECTION
subjects affected / exposed	3 / 334 (0.90%)	2 / 332 (0.60%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 3	1 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CELLULITIS
subjects affected / exposed	1 / 334 (0.30%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
CHRONIC HEPATITIS C
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
SEPTIC SHOCK
subjects affected / exposed	1 / 334 (0.30%)	1 / 332 (0.30%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	1 / 1	0 / 1	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 1	1 / 2
ENDOCARDITIS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
HYPONATRAEMIA
subjects affected / exposed	3 / 334 (0.90%)	1 / 332 (0.30%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	1 / 3	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERCALCAEMIA
subjects affected / exposed	2 / 334 (0.60%)	2 / 332 (0.60%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 2	0 / 2	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
FAILURE TO THRIVE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERGLYCAEMIA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DEHYDRATION
subjects affected / exposed	2 / 334 (0.60%)	4 / 332 (1.20%)	3 / 334 (0.90%)
occurrences causally related to treatment / all	2 / 2	4 / 4	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOKALAEMIA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOMAGNESAEMIA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DECREASED APPETITE
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPERKALAEMIA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
HYPOCALCAEMIA
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	2 / 334 (0.60%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
DIABETES MELLITUS
subjects affected / exposed	0 / 334 (0.00%)	1 / 332 (0.30%)	0 / 334 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
TYPE 2 DIABETES MELLITUS
subjects affected / exposed	0 / 334 (0.00%)	0 / 332 (0.00%)	1 / 334 (0.30%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Arm C: Nab-Paclitaxel + Carboplatin	Arm A: Atezolizumab + Paclitaxel + Carboplatin	Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin
Total subjects affected by non serious adverse events
subjects affected / exposed	315 / 334 (94.31%)	315 / 332 (94.88%)	325 / 334 (97.31%)
Vascular disorders
HYPOTENSION
subjects affected / exposed	12 / 334 (3.59%)	22 / 332 (6.63%)	18 / 334 (5.39%)
occurrences all number	18	25	25
General disorders and administration site conditions
PYREXIA
subjects affected / exposed	34 / 334 (10.18%)	46 / 332 (13.86%)	45 / 334 (13.47%)
occurrences all number	42	68	66
FATIGUE
subjects affected / exposed	88 / 334 (26.35%)	97 / 332 (29.22%)	107 / 334 (32.04%)
occurrences all number	101	112	137
ASTHENIA
subjects affected / exposed	66 / 334 (19.76%)	77 / 332 (23.19%)	58 / 334 (17.37%)
occurrences all number	85	101	81
CHEST PAIN
subjects affected / exposed	18 / 334 (5.39%)	28 / 332 (8.43%)	25 / 334 (7.49%)
occurrences all number	19	35	31
MUCOSAL INFLAMMATION
subjects affected / exposed	9 / 334 (2.69%)	17 / 332 (5.12%)	16 / 334 (4.79%)
occurrences all number	11	17	23
MALAISE
subjects affected / exposed	16 / 334 (4.79%)	10 / 332 (3.01%)	18 / 334 (5.39%)
occurrences all number	24	14	26
OEDEMA PERIPHERAL
subjects affected / exposed	22 / 334 (6.59%)	23 / 332 (6.93%)	25 / 334 (7.49%)
occurrences all number	25	28	32
Respiratory, thoracic and mediastinal disorders
DYSPHONIA
subjects affected / exposed	11 / 334 (3.29%)	17 / 332 (5.12%)	19 / 334 (5.69%)
occurrences all number	11	17	20
DYSPNOEA
subjects affected / exposed	57 / 334 (17.07%)	64 / 332 (19.28%)	68 / 334 (20.36%)
occurrences all number	65	75	100
EPISTAXIS
subjects affected / exposed	37 / 334 (11.08%)	8 / 332 (2.41%)	34 / 334 (10.18%)
occurrences all number	43	9	44
HAEMOPTYSIS
subjects affected / exposed	18 / 334 (5.39%)	18 / 332 (5.42%)	19 / 334 (5.69%)
occurrences all number	27	20	29
COUGH
subjects affected / exposed	51 / 334 (15.27%)	62 / 332 (18.67%)	65 / 334 (19.46%)
occurrences all number	61	69	85
Psychiatric disorders
INSOMNIA
subjects affected / exposed	27 / 334 (8.08%)	29 / 332 (8.73%)	30 / 334 (8.98%)
occurrences all number	28	32	34
ANXIETY
subjects affected / exposed	10 / 334 (2.99%)	17 / 332 (5.12%)	9 / 334 (2.69%)
occurrences all number	10	17	10
Investigations
PLATELET COUNT DECREASED
subjects affected / exposed	59 / 334 (17.66%)	40 / 332 (12.05%)	59 / 334 (17.66%)
occurrences all number	110	64	128
NEUTROPHIL COUNT DECREASED
subjects affected / exposed	65 / 334 (19.46%)	18 / 332 (5.42%)	60 / 334 (17.96%)
occurrences all number	144	25	132
BLOOD CREATININE INCREASED
subjects affected / exposed	3 / 334 (0.90%)	16 / 332 (4.82%)	25 / 334 (7.49%)
occurrences all number	4	16	28
BLOOD ALKALINE PHOSPHATASE INCREASED
subjects affected / exposed	8 / 334 (2.40%)	25 / 332 (7.53%)	17 / 334 (5.09%)
occurrences all number	8	33	18
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	17 / 334 (5.09%)	31 / 332 (9.34%)	34 / 334 (10.18%)
occurrences all number	27	56	64
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	18 / 334 (5.39%)	34 / 332 (10.24%)	40 / 334 (11.98%)
occurrences all number	23	56	64
WHITE BLOOD CELL COUNT DECREASED
subjects affected / exposed	36 / 334 (10.78%)	12 / 332 (3.61%)	32 / 334 (9.58%)
occurrences all number	68	19	64
WEIGHT DECREASED
subjects affected / exposed	14 / 334 (4.19%)	21 / 332 (6.33%)	32 / 334 (9.58%)
occurrences all number	14	22	38
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
subjects affected / exposed	30 / 334 (8.98%)	55 / 332 (16.57%)	48 / 334 (14.37%)
occurrences all number	35	68	54
DYSGEUSIA
subjects affected / exposed	22 / 334 (6.59%)	15 / 332 (4.52%)	26 / 334 (7.78%)
occurrences all number	22	15	30
HEADACHE
subjects affected / exposed	18 / 334 (5.39%)	38 / 332 (11.45%)	33 / 334 (9.88%)
occurrences all number	26	44	40
PARAESTHESIA
subjects affected / exposed	15 / 334 (4.49%)	28 / 332 (8.43%)	16 / 334 (4.79%)
occurrences all number	16	33	17
DIZZINESS
subjects affected / exposed	33 / 334 (9.88%)	33 / 332 (9.94%)	32 / 334 (9.58%)
occurrences all number	42	35	38
NEUROPATHY PERIPHERAL
subjects affected / exposed	36 / 334 (10.78%)	66 / 332 (19.88%)	34 / 334 (10.18%)
occurrences all number	39	73	39
Blood and lymphatic system disorders
NEUTROPENIA
subjects affected / exposed	124 / 334 (37.13%)	43 / 332 (12.95%)	121 / 334 (36.23%)
occurrences all number	214	61	261
ANAEMIA
subjects affected / exposed	193 / 334 (57.78%)	131 / 332 (39.46%)	188 / 334 (56.29%)
occurrences all number	244	153	257
THROMBOCYTOPENIA
subjects affected / exposed	92 / 334 (27.54%)	46 / 332 (13.86%)	91 / 334 (27.25%)
occurrences all number	171	66	163
LEUKOPENIA
subjects affected / exposed	34 / 334 (10.18%)	8 / 332 (2.41%)	42 / 334 (12.57%)
occurrences all number	54	8	86
Gastrointestinal disorders
CONSTIPATION
subjects affected / exposed	73 / 334 (21.86%)	75 / 332 (22.59%)	101 / 334 (30.24%)
occurrences all number	85	94	126
VOMITING
subjects affected / exposed	48 / 334 (14.37%)	50 / 332 (15.06%)	67 / 334 (20.06%)
occurrences all number	59	64	88
DIARRHOEA
subjects affected / exposed	77 / 334 (23.05%)	94 / 332 (28.31%)	92 / 334 (27.54%)
occurrences all number	107	116	135
NAUSEA
subjects affected / exposed	97 / 334 (29.04%)	94 / 332 (28.31%)	131 / 334 (39.22%)
occurrences all number	137	139	206
STOMATITIS
subjects affected / exposed	15 / 334 (4.49%)	20 / 332 (6.02%)	22 / 334 (6.59%)
occurrences all number	17	24	27
ABDOMINAL PAIN
subjects affected / exposed	8 / 334 (2.40%)	18 / 332 (5.42%)	9 / 334 (2.69%)
occurrences all number	8	20	13
ABDOMINAL PAIN UPPER
subjects affected / exposed	17 / 334 (5.09%)	12 / 332 (3.61%)	13 / 334 (3.89%)
occurrences all number	17	15	17
Skin and subcutaneous tissue disorders
RASH
subjects affected / exposed	18 / 334 (5.39%)	44 / 332 (13.25%)	47 / 334 (14.07%)
occurrences all number	19	57	55
PRURITUS
subjects affected / exposed	13 / 334 (3.89%)	32 / 332 (9.64%)	24 / 334 (7.19%)
occurrences all number	14	42	36
ALOPECIA
subjects affected / exposed	102 / 334 (30.54%)	130 / 332 (39.16%)	114 / 334 (34.13%)
occurrences all number	103	134	114
DRY SKIN
subjects affected / exposed	5 / 334 (1.50%)	13 / 332 (3.92%)	19 / 334 (5.69%)
occurrences all number	5	14	21
Endocrine disorders
HYPOTHYROIDISM
subjects affected / exposed	2 / 334 (0.60%)	27 / 332 (8.13%)	34 / 334 (10.18%)
occurrences all number	2	30	40
Musculoskeletal and connective tissue disorders
BACK PAIN
subjects affected / exposed	16 / 334 (4.79%)	33 / 332 (9.94%)	35 / 334 (10.48%)
occurrences all number	17	38	40
BONE PAIN
subjects affected / exposed	3 / 334 (0.90%)	23 / 332 (6.93%)	11 / 334 (3.29%)
occurrences all number	3	36	14
ARTHRALGIA
subjects affected / exposed	33 / 334 (9.88%)	78 / 332 (23.49%)	53 / 334 (15.87%)
occurrences all number	37	107	78
MYALGIA
subjects affected / exposed	19 / 334 (5.69%)	44 / 332 (13.25%)	22 / 334 (6.59%)
occurrences all number	24	63	23
PAIN IN EXTREMITY
subjects affected / exposed	17 / 334 (5.09%)	35 / 332 (10.54%)	32 / 334 (9.58%)
occurrences all number	17	48	35
Infections and infestations
RESPIRATORY TRACT INFECTION
subjects affected / exposed	6 / 334 (1.80%)	25 / 332 (7.53%)	10 / 334 (2.99%)
occurrences all number	6	38	17
NASOPHARYNGITIS
subjects affected / exposed	9 / 334 (2.69%)	23 / 332 (6.93%)	21 / 334 (6.29%)
occurrences all number	11	35	28
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	6 / 334 (1.80%)	18 / 332 (5.42%)	18 / 334 (5.39%)
occurrences all number	6	30	24
PNEUMONIA
subjects affected / exposed	16 / 334 (4.79%)	23 / 332 (6.93%)	29 / 334 (8.68%)
occurrences all number	19	28	30
URINARY TRACT INFECTION
subjects affected / exposed	16 / 334 (4.79%)	18 / 332 (5.42%)	26 / 334 (7.78%)
occurrences all number	20	27	45
Metabolism and nutrition disorders
HYPONATRAEMIA
subjects affected / exposed	5 / 334 (1.50%)	17 / 332 (5.12%)	11 / 334 (3.29%)
occurrences all number	5	22	17
HYPERGLYCAEMIA
subjects affected / exposed	17 / 334 (5.09%)	25 / 332 (7.53%)	18 / 334 (5.39%)
occurrences all number	19	28	29
DEHYDRATION
subjects affected / exposed	11 / 334 (3.29%)	20 / 332 (6.02%)	23 / 334 (6.89%)
occurrences all number	15	30	33
HYPOKALAEMIA
subjects affected / exposed	23 / 334 (6.89%)	24 / 332 (7.23%)	30 / 334 (8.98%)
occurrences all number	28	30	39
HYPOMAGNESAEMIA
subjects affected / exposed	38 / 334 (11.38%)	35 / 332 (10.54%)	54 / 334 (16.17%)
occurrences all number	56	47	91
DECREASED APPETITE
subjects affected / exposed	84 / 334 (25.15%)	93 / 332 (28.01%)	82 / 334 (24.55%)
occurrences all number	98	109	110

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Were there any global substantial amendments to the protocol? Yes

29 Mar 2015

Protocol was amended to clarify the inclusion criterion on contraception. In addition, reporting for serious adverse events and adverse events of special interest has been extended to 90 days after last dose of study treatment or until intitation of a new anticancer therapy, whichever occurs first.

14 Aug 2015

Protocol was amended to update the contraception requirements in the inclusion and exclusion criteria and the pregnancy-reporting information to be consistent with safety information for nab-paclitaxel. The study inclusion criteria have been modified, on the basis of an expanding safety database, to allow for patients with treated, asymptomatic cerebellar metastases to be enrolled provided specific criteria are met. The exclusion criteria for history of autoimmune disease has been broadened, on the basis of an expanding safety database, to allow for patients with eczema, psoriasis, or lichen simplex chronicus of vitiligo with dermatologic manifestations only to be permitted provided that they meet the specific conditions. The study exclusion criteria regarding treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug (whichever is shorter) prior to randomization has been modified to 4 weeks prior to randomization for consistency with more recent atezolizumab protocols. The exclusion criterion specifying that patients with a history of allergic reaction to intravenous contrast that requires steroid pretreatment should have baseline and subsequent tumor assessments performed via magnetic resonance imaging (MRI) has been removed.

11 Nov 2015

Protocol was amended to clarify that a wash-out period of at least 4 weeks or five half-lives, whichever is longer, of any systemic immunomodulatory agent is required prior to enrollment.

15 Jun 2016

Protocol was amended to add a co-primary endpoint of overall survival (OS) to the progression-free survival (PFS) primary endpoint. A secondary efficacy objective and outcome measure was added to evaluate the efficacy of atezolizumab + carboplatin + nab-paclitaxel compared with carboplatin + nab-paclitaxel as measured by investigator-assessed time to response (TTR) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) for both the ITT and PD-L1−selected populations. The inclusion criteria was modified to specify that patients who have received prior radiotherapy with curative intent must be treatment-free for at least a 6-month interval prior to randomization. Based on the half-life of atezolizumab of 27 days, the language regarding length of female patient contraception and follow-up of pregnancy reporting has been revised from 90 days to 5 months. The contraception requirements for male patients and pregnancy-reporting requirements for female partners of male patients who receive atezolizumab have been updated on the basis of the safety information for atezolizumab.

01 Mar 2017

Protocol was amended to include changes in the primary analysis populations fr the co-primary endpoints of progression-free survival (PFS) and overall survival (OS). OS will be analyzed in the intent-to-treat (ITT) population, PFS will be analyzed in the ITT population with a defined level of expression of a PD-L1 and T-effector gene signature in tumor tissue as determined by an RNA-based assay.

24 Oct 2018

Protocol was amended to include correction to the end of study definition. This correction ensures that the study continues until last patient, last visit or until the Sponsor terminates the stud. Inclusion criterion has been modified to address female contraception to specify when women must refrain from donating eggs.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population

Primary: Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population

Primary: Overall Survival (OS) in the ITT Population

Primary: Overall Survival (OS) in the ITT Population

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population

Secondary: OS in the TC2/3 or IC2/3 Population

Secondary: OS in the TC2/3 or IC2/3 Population

Secondary: OS in the TC1/2/3 or IC1/2/3 Population

Secondary: OS in the TC1/2/3 or IC1/2/3 Population

Secondary: Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

Secondary: Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

Secondary: Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

Secondary: Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

Secondary: Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population

Secondary: Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population

Secondary: TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population

Secondary: TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population

Secondary: Change from Baseline in Patient-reported Lung Cancer Symptoms Score using the SILC Scale Symptom Severity Score in the ITT Population

Secondary: Change from Baseline in Patient-reported Lung Cancer Symptoms Score using the SILC Scale Symptom Severity Score in the ITT Population

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A and Arm B)

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A and Arm B)

Secondary: OS in the ITT Population (Arm A and Arm B)

Secondary: OS in the ITT Population (Arm A and Arm B)

Secondary: Percentage of Participants With Adverse Events

Secondary: Percentage of Participants With Adverse Events

Secondary: Percentage of Participants with Anti-therapeutic Antibody (ATA) Response to Atezolizumab

Secondary: Percentage of Participants with Anti-therapeutic Antibody (ATA) Response to Atezolizumab

Secondary: Maximum Observed Serum Atezolizumab Concentration (Cmax)

Secondary: Maximum Observed Serum Atezolizumab Concentration (Cmax)

Secondary: Minimum Observed Serum Atezolizumab Concentration (Cmin)

Secondary: Minimum Observed Serum Atezolizumab Concentration (Cmin)

Secondary: Plasma Concentrations for Paclitaxel

Secondary: Plasma Concentrations for Paclitaxel

Secondary: Plasma Concentrations for Nab-Paclitaxel

Secondary: Plasma Concentrations for Nab-Paclitaxel

Secondary: Plasma Concentrations for Carboplatin

Secondary: Plasma Concentrations for Carboplatin

Secondary: OS in the in the Teff Population

Secondary: OS in the in the Teff Population

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population

Secondary: PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population

Secondary: Event Free Rate at 1 and 2 Years in the ITT Population

Secondary: Event Free Rate at 1 and 2 Years in the ITT Population

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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