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    Clinical Trial Results:
    A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-Pd-L1 Antibody) in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Patients Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer

    Summary
    EudraCT number
    		 2015-003605-42
    Trial protocol
    		 ES   RO   BE   LT   SK   PT   HU   AT   LV   FR   NL   HR   IT  
    Global end of trial date
    13 Dec 2022

    Results information
    Results version number
    		 v4(current)
    This version publication date
    22 Nov 2023
    First version publication date
    23 Jul 2020
    Other versions
    		 v1 , v2 , v3
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    GO29438
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02657434
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland,
    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
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    13 Dec 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Dec 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study is to evaluate the efficacy and safety of atezolizumab in combination with carboplatin or cisplatin + pemetrexed compared with carboplatin or cisplatin+ pemetrexed in subjects who are chemotherapy-naive and have Stage IV non-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
    07 Apr 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Australia: 25
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    Belgium: 6
    Country: Number of subjects enrolled
    Bulgaria: 1
    Country: Number of subjects enrolled
    Chile: 12
    Country: Number of subjects enrolled
    Spain: 118
    Country: Number of subjects enrolled
    France: 47
    Country: Number of subjects enrolled
    United Kingdom: 40
    Country: Number of subjects enrolled
    Hungary: 17
    Country: Number of subjects enrolled
    Ireland: 2
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Italy: 30
    Country: Number of subjects enrolled
    Japan: 101
    Country: Number of subjects enrolled
    Korea, Republic of: 14
    Country: Number of subjects enrolled
    Lithuania: 3
    Country: Number of subjects enrolled
    Latvia: 5
    Country: Number of subjects enrolled
    Malaysia: 7
    Country: Number of subjects enrolled
    Netherlands: 12
    Country: Number of subjects enrolled
    Peru: 1
    Country: Number of subjects enrolled
    Portugal: 8
    Country: Number of subjects enrolled
    Romania: 5
    Country: Number of subjects enrolled
    Russian Federation: 9
    Country: Number of subjects enrolled
    Taiwan: 10
    Country: Number of subjects enrolled
    Ukraine: 33
    Country: Number of subjects enrolled
    United States: 59
    Worldwide total number of subjects
    578
    EEA total number of subjects
    255
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    321
    From 65 to 84 years
    256
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study included chemotherapy-naive subjects with histologically or cytologically confirmed Stage IV non-squamous non-small cell lung cancer (NSCLC).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed)
    Arm description
    		 Participants received IV infusion of 500 mg/m^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who did not experience disease progression during the induction phase began maintenance therapy. Participants will receive IV infusion of 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
    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 - induction treatment: AUC of 6 mg/mL/min by IV infusion q3w for 4 or 6 cycles

    Investigational medicinal product name
    Pemetrexed
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed - induction treatment: 500 mg/m2 q3w by IV infusion for 4 or 6 cycles. Pemetrexed - maintenance treatment: 500 mg/m2 q3w by IV infusion until progressive disease.

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cisplatin - induction treatment: 75 mg/m2 by IV infusion q3w for 4 or 6 cycles

    Arm title
    		 Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Arm description
    		 Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.
    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 - induction treatment: 1200 mg by IV infusion for 4 – 6 cycles of 21 days (q3w). Atezolizumab - maintenance treatment: 1200 mg by IV infusion q3w until progressive disease or loss of clinical benefit.

    Investigational medicinal product name
    Pemetrexed
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed - induction treatment: 500 mg/m2 q3w by IV infusion for 4 or 6 cycles. Pemetrexed - maintenance treatment: 500 mg/m2 q3w by IV infusion until progressive disease.

    Investigational medicinal product name
    Cisplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cisplatin - induction treatment: 75 mg/m2 by IV infusion q3w for 4 or 6 cycles

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin - induction treatment: AUC of 6 mg/mL/min by IV infusion q3w for 4 or 6 cycles

    Number of subjects in period 1
    		Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Started
    286
    292
    Completed
    0
    0
    Not completed
    286
    292
         Consent withdrawn by subject
    28
    17
         Physician decision
    -
    1
         Study terminated by Sponsor
    64
    82
         Death
    189
    190
         Lost to follow-up
    2
    2
         Randomization by error
    2
    -
         Protocol deviation
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm B (Carboplatin or Cisplatin + Pemetrexed)
    Reporting group description
    		 Participants received IV infusion of 500 mg/m^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who did not experience disease progression during the induction phase began maintenance therapy. Participants will receive IV infusion of 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.

    Reporting group title
    Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Reporting group description
    		 Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.

    Reporting group values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed Total
    Number of subjects
    		 286 292 578
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 168 153 321
        From 65-84 years
    		 118 138 256
        85 years and over
    		 0 1 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 61.8 ( 9.4 ) 63.3 ( 9.4 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 94 100 194
        Male
    		 192 192 384
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 1 2
        Asian
    		 65 71 136
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 4 2 6
        White
    		 203 193 396
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 13 25 38
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 21 17 38
        Not Hispanic or Latino
    		 241 243 484
        Unknown or Not Reported
    		 24 32 56

    End points

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    End points reporting groups
    Reporting group title
    Arm B (Carboplatin or Cisplatin + Pemetrexed)
    Reporting group description
    		 Participants received IV infusion of 500 mg/m^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who did not experience disease progression during the induction phase began maintenance therapy. Participants will receive IV infusion of 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.

    Reporting group title
    Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Reporting group description
    		 Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.

    Primary: Progression Free Survival (PFS) as assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

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    End point title
    		 Progression Free Survival (PFS) as assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
    End point description
    PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurred first.
    End point type
    Primary
    End point timeframe
    Randomization up to approximately 39 months
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    286
    292
    Units: Months
        median (confidence interval 95%)
    5.2 (4.3 to 5.6)
    7.7 (6.7 to 8.5)
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    Unstratified Analysis
    Comparison groups
    Arm B (Carboplatin or Cisplatin + Pemetrexed) v Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 Logrank
    Parameter type
    		 Log hazard ratio
    Point estimate
    0.562
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.471
         upper limit
    		 0.671

    Primary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS is defined as time from randomization to death from any cause.
    End point type
    Primary
    End point timeframe
    Randomization up to approximately 39 months
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    286
    292
    Units: Months
        median (confidence interval 95%)
    13.6 (11.0 to 15.7)
    17.5 (13.2 to 19.6)
    Statistical analysis title
    		 OS Statistical Analysis (Unstratified Analysis)
    Comparison groups
    Arm B (Carboplatin or Cisplatin + Pemetrexed) v Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1559
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.866
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.709
         upper limit
    		 1.056
    Statistical analysis title
    		 OS Statistical Analysis (Stratified Analysis)
    Comparison groups
    Arm B (Carboplatin or Cisplatin + Pemetrexed) v Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1546
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.864
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.707
         upper limit
    		 1.056

    Secondary: Overall Survival Rate Year 2

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    End point title
    		 Overall Survival Rate Year 2
    End point description
    The Overall Survival Rate at the 2-year landmark time point is defined as the probabilities that participants are alive 2-years after randomization.
    End point type
    Secondary
    End point timeframe
    Year 2
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    91
    109
    Units: Percentage
        number (confidence interval 95%)
    34.01 (28.40 to 39.62)
    39.13 (33.44 to 44.81)
    Statistical analysis title
    		 OS Rate at 2 Year Statistical Analysis
    Comparison groups
    Arm B (Carboplatin or Cisplatin + Pemetrexed) v Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects included in analysis
    200
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.209
    Method
    		 Z-test
    Parameter type
    		 Difference in Event Free Rate
    Point estimate
    5.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.87
         upper limit
    		 13.11

    Secondary: Overall Survival Rate at Year 1

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    End point title
    		 Overall Survival Rate at Year 1
    End point description
    The Overall Survival Rate at the 1-year landmark time point is defined as the probabilities that participants are alive 1-year after randomization.
    End point type
    Secondary
    End point timeframe
    Year 1
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    286
    292
    Units: Percentage
        number (confidence interval 95%)
    55.04 (49.21 to 60.87)
    59.72 (54.02 to 65.41)
    Statistical analysis title
    		 OS Rate at 1 Year Statistical Analysis
    Comparison groups
    Arm B (Carboplatin or Cisplatin + Pemetrexed) v Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.2606
    Method
    		 z test
    Parameter type
    		 Difference in event free rate
    Point estimate
    4.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.47
         upper limit
    		 12.83

    Secondary: Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1

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    End point title
    		 Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1
    End point description
    DOR is defined as the time interval from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented, whichever occurs first.
    End point type
    Secondary
    End point timeframe
    Randomization up to approximately 25 months
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    286
    292
    Units: Months
        number (confidence interval 95%)
    6.4 (4.4 to 7.6)
    9.5 (6.9 to 12.2)
    Statistical analysis title
    		 DOR Statistical Analysis
    Comparison groups
    Arm B (Carboplatin or Cisplatin + Pemetrexed) v Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0024
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.62
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 0.85

    Secondary: Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using RECIST V1.1

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    End point title
    		 Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using RECIST V1.1
    End point description
    An objective response is defined as either an unconfirmed CR or a PR, as determined by the investigator using RECIST v1.1. Objective Response Rate is defined as the proportion of patients who had an objective response.
    End point type
    Secondary
    End point timeframe
    Randomization up to approximately 25 months
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    286
    292
    Units: Percentage of Participants
    number (not applicable)
        Responders
    37.4
    51.7
        Non-Responders
    62.6
    48.3
    Statistical analysis title
    		 Objective Response Statistical Analysis
    Comparison groups
    Arm B (Carboplatin or Cisplatin + Pemetrexed) v Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects included in analysis
    578
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0005
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in response rate
    Point estimate
    14.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.9
         upper limit
    		 22.7

    Secondary: Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score

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    End point title
    		 Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score
    End point description
    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 QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998). Note: 999999=not available. FU=Follow-Up.
    End point type
    Secondary
    End point timeframe
    Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    232
    242
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Dyspnoea: Week 3 (Arm B n=222)(Arm A n=216)
    -1.95 ( 23.97 )
    -1.39 ( 25.17 )
        Dyspnoea: Week 6 (Arm B n=189)(Arm A n=198)
    -1.23 ( 23.16 )
    -4.71 ( 26.66 )
        Dyspnoea: Week 9 (Arm B n=166)(Arm A n=179)
    0.20 ( 26.34 )
    -6.33 ( 26.62 )
        Dyspnoea: Week 12 (Arm B n=147)(Arm A n=177)
    -0.91 ( 27.57 )
    -3.39 ( 29.10 )
        Dyspnoea: Week 15 (Arm B n=140)(Arm A n=164)
    -1.67 ( 28.92 )
    -2.44 ( 28.73 )
        Dyspnoea: Week 18 (Arm B n=126)(Arm A n=155)
    -2.12 ( 24.85 )
    -3.44 ( 30.43 )
        Dyspnoea: Week 21 (Arm B n=100)(Arm A n=150)
    -5.67 ( 29.61 )
    -2.89 ( 31.83 )
        Dyspnoea: Week 24 (Arm B n=97)(Arm A n=136)
    -2.75 ( 28.74 )
    -2.45 ( 31.85 )
        Dyspnoea: Week 27 (Arm B n=79)(Arm A n=126)
    -2.53 ( 31.47 )
    -1.32 ( 27.13 )
        Dyspnoea: Week 30 (Arm B n=80)(Arm A n=123)
    -1.25 ( 32.45 )
    -2.71 ( 28.50 )
        Dyspnoea: Week 33 (Arm B n=73)(Arm A n=107)
    -1.83 ( 27.15 )
    -3.74 ( 30.14 )
        Dyspnoea: Week 36 (Arm B n=61)(Arm A n=105)
    -3.83 ( 30.49 )
    -6.67 ( 31.49 )
        Dyspnoea: Week 39 (Arm B n=60)(Arm A n=95)
    -1.67 ( 31.55 )
    -8.42 ( 29.16 )
        Dyspnoea: Week 42 (Arm B n=51)(Arm A n=95)
    -3.27 ( 28.48 )
    -9.12 ( 28.12 )
        Dyspnoea: Week 45 (Arm B n=48)(Arm A n=79)
    -6.25 ( 32.00 )
    -2.11 ( 30.82 )
        Dyspnoea: Week 48 (Arm B n=39)(Arm A n=81)
    -5.13 ( 32.03 )
    -7.41 ( 26.87 )
        Dyspnoea: Week 51(Arm B n=36)(Arm A n=80)
    -14.81 ( 30.28 )
    -2.92 ( 26.09 )
        Dyspnoea: Week 54 (Arm B n=31)(Arm A n=72)
    -9.68 ( 35.69 )
    -2.78 ( 27.26 )
        Dyspnoea: Week 57 (Arm B n=26)(Arm A n=71)
    -7.69 ( 28.76 )
    -5.63 ( 28.72 )
        Dyspnoea: Week 60 (Arm B n=18)(Arm A n=56)
    -11.11 ( 25.57 )
    0.00 ( 25.43 )
        Dyspnoea: Week 63 (Arm B n=13)(Arm A n=39)
    -7.69 ( 14.62 )
    -5.13 ( 23.62 )
        Dyspnoea: Week 66 (Arm B n=7)(Arm A n=37)
    -9.52 ( 16.27 )
    -1.80 ( 24.78 )
        Dyspnoea: Week 69 (Arm B n=6)(Arm A n=28)
    -16.67 ( 18.26 )
    -3.57 ( 24.58 )
        Dyspnoea: Week 72 (Arm B n=8)(Arm A n=22)
    -4.17 ( 27.82 )
    0.00 ( 27.22 )
        Dyspnoea: Week 75 (Arm B n=5)(Arm A n=23)
    -6.67 ( 14.91 )
    -5.80 ( 19.21 )
        Dyspnoea: Week 78 (Arm B n=2)(Arm A n=14)
    0.00 ( 0.00 )
    -4.76 ( 25.68 )
        Dyspnoea: Week 81 (Arm B n=2)(Arm A n=9)
    0.00 ( 0.00 )
    -11.11 ( 23.57 )
        Dyspnoea: Week 84 (Arm B n=2)(Arm A n=8)
    0.00 ( 0.00 )
    -4.17 ( 21.36 )
        Dyspnoea: Week 87 (Arm B n=1)(Arm A n=4)
    0.00 ( 999999 )
    8.33 ( 16.67 )
        Dyspnoea: Week 90 (Arm B n=1)(Arm A n=2)
    0.00 ( 999999 )
    0.00 ( 0.00 )
        Dyspnoea: Week 93 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    0.00 ( 999999 )
        Dyspnoea: Time of First Pd (Arm B n=0)(Arm A n=0)
    999999 ( 999999 )
    999999 ( 999999 )
        Dyspnoea:Time of Last Tx Dose Arm B n=0;Arm A n=0
    999999 ( 999999 )
    999999 ( 999999 )
        Dyspnoea:Survival FU Wk 12 Arm B n=29;Arm A n=25
    9.20 ( 35.52 )
    8.00 ( 42.25 )
        Dyspnoea:Survival FU Wk 24 Arm B n=19;Arm A n=7
    5.26 ( 25.49 )
    -14.29 ( 17.82 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score

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    End point title
    		 Change from Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score
    End point description
    The EORTC QLQ-LC13 module incorporates one multiple item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998). Note: 999999=not available. ToL=Time of Last. ToF=Time of First. Sur=survival.
    End point type
    Secondary
    End point timeframe
    Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    230
    234
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Coughing: Week 3 (Arm B n=213)(Arm A n=205)
    -2.50 ( 25.37 )
    -3.41 ( 26.90 )
        Coughing: Week 6 (Arm B n=187)(Arm A n=190)
    -3.57 ( 27.20 )
    -9.82 ( 26.50 )
        Coughing: Week 9 (Arm B n=162)(Arm A n=173)
    -1.85 ( 24.43 )
    -8.29 ( 31.37 )
        Coughing: Week 12 (Arm B n=145)(Arm A n=168)
    -3.91 ( 28.46 )
    -10.71 ( 31.66 )
        Coughing: Week 15 (Arm B n=137)(Arm A n=159)
    -6.33 ( 30.39 )
    -11.53 ( 29.05 )
        Coughing: Week 18 (Arm B n=125)(Arm A n=149)
    -4.00 ( 26.97 )
    -11.63 ( 27.92 )
        Coughing: Week 21 (Arm B n=100)(Arm A n=146)
    -6.00 ( 27.78 )
    -10.50 ( 30.76 )
        Coughing: Week 24 (Arm B n=97)(Arm A n=133)
    -4.81 ( 28.05 )
    -10.03 ( 33.08 )
        Coughing: Week 27 (Arm B n=78)(Arm A n=123)
    -3.85 ( 26.85 )
    -11.65 ( 34.40 )
        Coughing: Week 30 (Arm B n=80)(Arm A n=120)
    0.42 ( 29.76 )
    -11.39 ( 31.31 )
        Coughing: Week 33 (Arm B n=72)(Arm A n=103)
    -0.46 ( 26.53 )
    -11.97 ( 30.91 )
        Coughing: Week 36 (Arm B n=60)(Arm A n=103)
    -6.11 ( 31.59 )
    -12.94 ( 30.33 )
        Coughing: Week 39 (Arm B n=60)(Arm A n=92)
    -5.00 ( 30.58 )
    -13.41 ( 32.43 )
        Coughing: Week 42 (Arm B n=52)(Arm A n=93)
    -8.97 ( 27.31 )
    -14.70 ( 29.68 )
        Coughing: Week 45 (Arm B n=48)(Arm A n=77)
    -13.19 ( 28.13 )
    -14.72 ( 27.83 )
        Coughing: Week 48 (Arm B n=39)(Arm A n=79)
    -7.69 ( 31.96 )
    -13.92 ( 32.29 )
        Coughing: Week 51 (Arm B n=36)(Arm A n=79)
    -17.59 ( 25.80 )
    -10.97 ( 34.48 )
        Coughing: Week 54 (Arm B n=31)(Arm A n=70)
    -17.20 ( 27.04 )
    -13.81 ( 33.81 )
        Coughing: Week 57 (Arm B n=26)(Arm A n=69)
    -11.54 ( 22.98 )
    -13.53 ( 29.33 )
        Coughing: Week 60 (Arm B n=19)(Arm A n=56)
    -14.04 ( 27.92 )
    -10.71 ( 31.21 )
        Coughing: Week 63 (Arm B n=13)(Arm A n=39)
    -10.26 ( 21.01 )
    -12.82 ( 27.16 )
        Coughing: Week 66 (Arm B n=7)(Arm A n=37)
    -9.52 ( 25.20 )
    -12.61 ( 28.71 )
        Coughing: Week 69 (Arm B n=6)(Arm A n=28)
    -11.11 ( 27.22 )
    -11.90 ( 30.38 )
        Coughing: Week 72 (Arm B n=8)(Arm A n=22)
    -8.33 ( 23.57 )
    -16.67 ( 30.43 )
        Coughing: Week 75 (Arm B n=5)(Arm A n=23)
    -13.33 ( 18.26 )
    -18.84 ( 28.12 )
        Coughing: Week 78 (Arm B n=2)(Arm A n=14)
    -16.67 ( 23.57 )
    -23.81 ( 27.51 )
        Coughing: Week 81 (Arm B n=2)(Arm A n=9)
    -16.67 ( 23.57 )
    -18.52 ( 33.79 )
        Coughing: Week 84 (Arm B n=2)(Arm A n=8)
    -33.33 ( 0.00 )
    -29.17 ( 27.82 )
        Coughing: Week 87 (Arm B n=1)(Arm A n=4)
    0.00 ( 999999 )
    -25.00 ( 31.91 )
        Coughing: Week 90 (Arm B n=1)(Arm A n=2)
    -33.33 ( 999999 )
    -16.67 ( 23.57 )
        Coughing: Week 93 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    0.00 ( 999999 )
        Coughing:Time of First Pd Arm B n=61;Arm A n=70
    -6.01 ( 30.13 )
    -10.48 ( 28.68 )
        Coughing:ToL Tx Dose Arm B n=199;Arm A n=201
    -5.19 ( 28.05 )
    -8.13 ( 28.78 )
        Coughing:Survival FU Wk 12 Arm B n=28,Arm A n=24
    3.57 ( 29.17 )
    -6.94 ( 34.02 )
        Coughing: Survival FU Wk 24 Arm B n=19,Arm A n=7
    -8.77 ( 24.45 )
    -14.29 ( 32.53 )
        Dyspnoea: Week 3 (Arm B n=213)(Arm A n=205)
    0.21 ( 18.69 )
    -1.41 ( 17.68 )
        Dyspnoea: Week 6 (Arm B n=187)(Arm A n=190)
    0.12 ( 17.13 )
    -1.17 ( 18.85 )
        Dyspnoea: Week 9 (Arm B n=162)(Arm A n=173)
    0.89 ( 20.68 )
    -3.34 ( 18.65 )
        Dyspnoea: Week 12 (Arm B n=145)(Arm A n=168)
    1.15 ( 21.82 )
    -0.46 ( 21.76 )
        Dyspnoea: Week 15 (Arm B n=137)(Arm A n=159)
    0.00 ( 21.30 )
    -1.12 ( 20.78 )
        Dyspnoea: Week 18 (Arm B n=125)(Arm A n=149)
    -1.07 ( 18.90 )
    -3.88 ( 21.92 )
        Dyspnoea: Week 21 (Arm B n=100)(Arm A n=146)
    -3.56 ( 22.77 )
    -1.45 ( 21.85 )
        Dyspnoea: Week 24 (Arm B n=97)(Arm A n=133)
    -2.29 ( 21.75 )
    -0.42 ( 23.82 )
        Dyspnoea: Week 27 (Arm B n=78)(Arm A n=123)
    -0.71 ( 22.32 )
    -2.08 ( 19.83 )
        Dyspnoea: Week 30 (Arm B n=80)(Arm A n=120)
    1.25 ( 22.57 )
    -2.78 ( 20.33 )
        Dyspnoea: Week 33 (Arm B n=72)(Arm A n=103)
    0.77 ( 21.45 )
    -3.02 ( 22.82 )
        Dyspnoea: Week 36 (Arm B n=60)(Arm A n=103)
    -1.11 ( 20.93 )
    -2.91 ( 23.70 )
        Dyspnoea: Week 39 (Arm B n=60)(Arm A n=92)
    1.30 ( 26.91 )
    -4.95 ( 22.31 )
        Dyspnoea: Week 42 (Arm B n=52)(Arm A n=93)
    -0.43 ( 22.65 )
    -6.33 ( 18.64 )
        Dyspnoea: Week 45 (Arm B n=48)(Arm A n=77)
    -2.08 ( 26.60 )
    -3.61 ( 21.36 )
        Dyspnoea: Week 48 (Arm B n=39)(Arm A n=79)
    -4.56 ( 24.94 )
    -5.34 ( 21.49 )
        Dyspnoea: Week 51 (Arm B n=36)(Arm A n=79)
    -9.88 ( 21.87 )
    -1.69 ( 18.41 )
        Dyspnoea: Week 54 (Arm B n=31)(Arm A n=70)
    -6.45 ( 24.47 )
    -1.90 ( 19.10 )
        Dyspnoea: Week 57 (Arm B n=26)(Arm A n=69)
    -2.99 ( 23.42 )
    -4.99 ( 22.99 )
        Dyspnoea: Week 60 (Arm B n=19)(Arm A n=56)
    -11.11 ( 23.42 )
    -0.40 ( 22.32 )
        Dyspnoea: Week 63 (Arm B n=13)(Arm A n=39)
    -6.84 ( 15.41 )
    -6.55 ( 23.04 )
        Dyspnoea: Week 66 (Arm B n=7)(Arm A n=37)
    -9.52 ( 16.27 )
    -4.50 ( 21.98 )
        Dyspnoea: Week 69 (Arm B n=6)(Arm A n=28)
    -16.67 ( 21.94 )
    -4.76 ( 23.12 )
        Dyspnoea: Week 72 (Arm B n=8)(Arm A n=22)
    -5.56 ( 19.70 )
    -1.52 ( 24.56 )
        Dyspnoea: Week 75 (Arm B n=5)(Arm A n=23)
    -6.67 ( 14.91 )
    -6.76 ( 17.64 )
        Dyspnoea: Week 78 (Arm B n=2)(Arm A n=14)
    0.00 ( 0.00 )
    -3.17 ( 21.09 )
        Dyspnoea: Week 81 (Arm B n=2)(Arm A n=9)
    11.11 ( 15.71 )
    -9.88 ( 22.53 )
        Dyspnoea: Week 84 (Arm B n=2)(Arm A n=8)
    0.00 ( 0.00 )
    -6.94 ( 22.17 )
        Dyspnoea: Week 87 (Arm B n=1)(Arm A n=4)
    0.00 ( 999999 )
    -2.78 ( 18.98 )
        Dyspnoea: Week 90 (Arm B n=1)(Arm A n=2)
    0.00 ( 999999 )
    5.56 ( 23.57 )
        Dyspnoea: Week 93 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    22.22 ( 999999 )
        Dyspnoea:Time of First PD Arm B n=61,Arm A n=70
    2.37 ( 22.05 )
    -0.16 ( 24.48 )
        Dyspnoea:ToL Tx Dose Arm B n=199, Arm A n=201
    3.96 ( 22.74 )
    0.44 ( 21.83 )
        Dyspnoea:Survival FU Wk 12 Arm B n=28,Arm A n=24
    9.92 ( 25.90 )
    13.43 ( 33.73 )
        Dyspnoea:Survival FU Wk 24 Arm B n=19,Arm A n=7
    4.68 ( 17.50 )
    4.76 ( 23.00 )
        Pain In Chest: Week 3 (Arm B n=213)(Arm A n=205)
    -1.25 ( 21.19 )
    0.81 ( 23.67 )
        Pain In Chest: Week 6 (Arm B n=187)(Arm A n=190)
    0.71 ( 25.15 )
    -6.32 ( 24.39 )
        Pain In Chest: Week 9 (Arm B n=162)(Arm A n=173)
    0.82 ( 24.63 )
    -4.24 ( 25.57 )
        Pain In Chest: Week 12 (Arm B n=145)(Arm A n=168)
    -2.07 ( 24.60 )
    -0.60 ( 27.65 )
        Pain In Chest: Week 15 (Arm B n=137)(Arm A n=159)
    -1.46 ( 24.88 )
    -3.56 ( 25.60 )
        Pain In Chest: Week 18 (Arm B n=125)(Arm A n=149)
    -3.47 ( 26.38 )
    -3.36 ( 26.77 )
        Pain In Chest: Week 21 (Arm B n=100)(Arm A n=146)
    -3.33 ( 26.17 )
    -2.74 ( 25.22 )
        Pain In Chest: Week 24 (Arm B n=97)(Arm A n=133)
    -2.41 ( 26.89 )
    -4.76 ( 29.05 )
        Pain In Chest: Week 27 (Arm B n=78)(Arm A n=123)
    -5.13 ( 29.95 )
    -2.71 ( 22.82 )
        Pain In Chest: Week 30 (Arm B n=80)(Arm A n=120)
    -4.17 ( 29.71 )
    -3.06 ( 27.33 )
        Pain In Chest: Week 33 (Arm B n=72)(Arm A n=103)
    -0.46 ( 29.86 )
    -3.88 ( 28.12 )
        Pain In Chest: Week 36 (Arm B n=60)(Arm A n=103)
    -1.67 ( 31.55 )
    -2.91 ( 27.26 )
        Pain In Chest: Week 39 (Arm B n=60)(Arm A n=92)
    -3.89 ( 30.12 )
    -3.99 ( 27.44 )
        Pain In Chest: Week 42 (Arm B n=52)(Arm A n=93)
    -7.69 ( 29.24 )
    -7.17 ( 26.40 )
        Pain In Chest: Week 45 (Arm B n=48)(Arm A n=77)
    -6.25 ( 29.70 )
    -5.63 ( 25.02 )
        Pain In Chest: Week 48 (Arm B n=39)(Arm A n=79)
    -7.69 ( 29.08 )
    -4.64 ( 24.88 )
        Pain In Chest: Week 51 (Arm B n=36)(Arm A n=79)
    -11.11 ( 28.73 )
    -5.49 ( 24.13 )
        Pain In Chest: Week 54 (Arm B n=31)(Arm A n=70)
    -7.53 ( 29.45 )
    -4.29 ( 25.33 )
        Pain In Chest: Week 57 (Arm B n=26)(Arm A n=69)
    -1.28 ( 31.95 )
    -5.80 ( 26.17 )
        Pain In Chest: Week 60 (Arm B n=19)(Arm A n=56)
    0.00 ( 22.22 )
    -3.57 ( 27.47 )
        Pain In Chest: Week 63 (Arm B n=13)(Arm A n=39)
    -5.13 ( 18.49 )
    -6.84 ( 25.57 )
        Pain In Chest: Week 66 (Arm B n=7)(Arm A n=37)
    -4.76 ( 23.00 )
    -4.50 ( 27.40 )
        Pain In Chest: Week 69 (Arm B n=6)(Arm A n=28)
    -16.67 ( 18.26 )
    -5.95 ( 31.50 )
        Pain In Chest: Week 72 (Arm B n=8)(Arm A n=22)
    -8.33 ( 23.57 )
    -4.55 ( 23.67 )
        Pain In Chest: Week 75 (Arm B n=5)(Arm A n=23)
    -6.67 ( 14.91 )
    0.00 ( 20.10 )
        Pain In Chest: Week 78 (Arm B n=2)(Arm A n=14)
    0.00 ( 0.00 )
    0.00 ( 26.15 )
        Pain In Chest: Week 81 (Arm B n=2)(Arm A n=9)
    0.00 ( 47.14 )
    7.41 ( 14.70 )
        Pain In Chest: Week 84 (Arm B n=2)(Arm A n=8)
    0.00 ( 0.00 )
    4.17 ( 21.36 )
        Pain In Chest: Week 87 (Arm B n=1)(Arm A n=4)
    -33.33 ( 999999 )
    8.33 ( 16.67 )
        Pain In Chest: Week 90 (Arm B n=1)(Arm A n=2)
    -33.33 ( 999999 )
    0.00 ( 0.00 )
        Pain In Chest: Week 93 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    0.00 ( 999999 )
        Pain In Chest: ToF Pd (Arm B n=61)(Arm A n=70)
    6.56 ( 22.62 )
    -3.81 ( 29.24 )
        Pain In Chest: ToL Tx Dose Arm B n=199 Arm A n=201
    1.34 ( 25.26 )
    -0.83 ( 26.96 )
        Pain In Chest:Sur FU Wk12 Arm B n=28 Arm A n=24
    5.95 ( 36.35 )
    -2.78 ( 32.48 )
        Pain In Chest: Sur FU Wk 24 Arm B n=19 Arm A n=7
    1.75 ( 17.48 )
    -4.76 ( 29.99 )
        Pain In Arm/Shoulder:Wk 3 Arm B n=213 Arm A n=205
    -4.69 ( 25.26 )
    -2.60 ( 24.78 )
        Pain In Arm/Shoulder: Wk 6 Arm B n=187 Arm A n=190
    -4.46 ( 23.14 )
    -5.44 ( 25.19 )
        Pain In Arm/Shoulder: Wk 9 Arm B n=162 Arm A n=173
    -2.88 ( 25.85 )
    -8.09 ( 28.73 )
        Pain In Arm/Shoulder: Wk12 Arm B n=145 Arm A n=168
    -6.90 ( 23.54 )
    -4.37 ( 27.19 )
        Pain In Arm/Shoulder:Wk 15 Arm B n=137 Arm A n=159
    -3.89 ( 23.24 )
    -7.34 ( 30.15 )
        Pain In Arm/Shoulder:Wk18 Arm B n=125 Arm A n=149
    -5.07 ( 25.77 )
    -6.26 ( 29.09 )
        Pain In Arm/Shoulder:Wk21 Arm B n=100 Arm A n=146
    -6.00 ( 21.91 )
    -1.83 ( 28.71 )
        Pain In Arm/Shoulder:Wk24 Arm B n=97 Arm A n=133
    -2.41 ( 28.16 )
    -5.26 ( 30.11 )
        Pain In Arm/Shoulder:Wk27 Arm B n=78 Arm A n=123
    -5.56 ( 28.13 )
    -3.79 ( 26.72 )
        Pain In Arm/Shoulder:Wk30 Arm B n=80 Arm A n=120
    1.25 ( 27.27 )
    -3.33 ( 29.12 )
        Pain In Arm/Shoulder:Wk33 Arm B n=72 Arm A n=103
    -5.56 ( 25.02 )
    -1.94 ( 27.54 )
        Pain In Arm/Shoulder:Wk36 Arm B n=60 Arm A n=103
    -1.67 ( 30.33 )
    -3.24 ( 31.49 )
        Pain In Arm/Shoulder:Wk39 (Arm B n=60)(Arm A n=92)
    -5.00 ( 30.58 )
    -3.99 ( 30.80 )
        Pain In Arm/Shoulder:Wk42 (Arm B n=52)(Arm A n=93)
    0.00 ( 28.77 )
    -8.60 ( 25.49 )
        Pain In Arm/Shoulder:Wk45 (Arm B n=48)(Arm A n=77)
    -0.69 ( 27.06 )
    -6.06 ( 28.47 )
        Pain In Arm/Shoulder:Wk48 (Arm B n=39)(Arm A n=79)
    -1.71 ( 27.52 )
    -4.22 ( 29.89 )
        Pain In Arm/Shoulder: Wk51 Arm B n=36 Arm A n=79
    -2.78 ( 25.67 )
    -3.38 ( 27.53 )
        Pain In Arm/Shoulder:Wk54 Arm B n=31 Arm A n=70
    -1.08 ( 21.92 )
    -6.19 ( 25.56 )
        Pain In Arm/Shoulder:Wk57 Arm B n=26 Arm A n=69
    -1.28 ( 22.07 )
    -2.90 ( 26.65 )
        Pain In Arm/Shoulder:Wk 60 Arm B n=19 Arm A n=56
    -5.26 ( 20.07 )
    -4.17 ( 27.75 )
        Pain In Arm/Shoulder:Wk 63 Arm B n=13 Arm A n=39
    -5.13 ( 18.49 )
    -3.42 ( 27.35 )
        Pain In Arm/Shoulder:Wk 66 Arm B n=7 Arm A n=37
    4.76 ( 12.60 )
    -1.80 ( 31.37 )
        Pain In Arm/Shoulder:Wk 69 Arm B n=6 Arm A n=28
    0.00 ( 0.00 )
    -7.14 ( 22.87 )
        Pain In Arm/Shoulder:Wk 72 Arm B n=8 Arm A n=22
    -8.33 ( 15.43 )
    -7.58 ( 27.08 )
        Pain In Arm/Shoulder:Wk 75 Arm B n=5 Arm A n=23
    -6.67 ( 14.91 )
    -8.70 ( 25.06 )
        Pain In Arm/Shoulder:Wk78 Arm B n=2 Arm A n=14
    0.00 ( 0.00 )
    -2.38 ( 24.33 )
        Pain In Arm/Shoulder:Wk 81 Arm B n=2 Arm A n=9
    0.00 ( 0.00 )
    3.70 ( 11.11 )
        Pain In Arm/Shoulder:Wk84 Arm B n=2 Arm A n=8
    0.00 ( 0.00 )
    4.17 ( 21.36 )
        Pain In Arm/Shoulder:Wk 87 Arm B n=1 Arm A n=4
    0.00 ( 999999 )
    -16.67 ( 33.33 )
        Pain In Arm/Shoulder:Wk 90 Arm B n=1 Arm A n=2
    0.00 ( 999999 )
    0.00 ( 0.00 )
        Pain In Arm/Shoulder:Wk 93 Arm B n=0 Arm A n=1
    999999 ( 999999 )
    0.00 ( 999999 )
        Pain In Arm/Shoulder: ToF Pd Arm B n=61 Arm A n=70
    2.19 ( 28.46 )
    1.90 ( 25.94 )
        Pain In Arm/Shoulder:ToLTxDose ArmBn=199 ArmAn=201
    -0.50 ( 27.11 )
    0.33 ( 30.55 )
        Pain In Arm/Shoulder:Sur FU Wk12 ArmBn=28 ArmAn=24
    13.10 ( 30.55 )
    5.56 ( 40.13 )
        Pain In Arm/Shoulder:Sur FU Wk24 ArmBn=19 ArmAn=7
    1.75 ( 28.27 )
    0.00 ( 0.00 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score

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    End point title
    		 Change from Baseline in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score
    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: 999999=not available. ToF=Time of First. ToL=Time of Last.
    End point type
    Secondary
    End point timeframe
    Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)
    End point values
    		 Arm B (Carboplatin or Cisplatin + Pemetrexed) Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    176
    200
    Units: Units on a scale
    arithmetic mean (standard deviation)
        Chest Pain: Week 1 (Arm B n=160)(Arm A n=186)
    0.20 ( 0.83 )
    0.30 ( 0.88 )
        Chest Pain: Week 2 (Arm B n=152)(Arm A n=176)
    -0.01 ( 0.88 )
    0.21 ( 0.85 )
        Chest Pain: Week 3 (Arm B n=151)(Arm A n=165)
    -0.05 ( 0.92 )
    0.06 ( 0.95 )
        Chest Pain: Week 4 (Arm B n=144)(Arm A n=160)
    0.03 ( 0.91 )
    0.03 ( 0.93 )
        Chest Pain: Week 5 (Arm B n=143)(Arm A n=166)
    -0.02 ( 0.93 )
    -0.01 ( 0.88 )
        Chest Pain: Week 6 (Arm B n=132)(Arm A n=166)
    -0.05 ( 0.88 )
    -0.02 ( 0.92 )
        Chest Pain: Week 7 (Arm B n=132)(Arm A n=156)
    0.07 ( 1.00 )
    -0.04 ( 1.00 )
        Chest Pain: Week 8 (Arm B n=124)(Arm A n=157)
    0.03 ( 0.94 )
    -0.07 ( 1.02 )
        Chest Pain: Week 9 (Arm B n=125)(Arm A n=159)
    0.06 ( 1.00 )
    -0.03 ( 1.03 )
        Chest Pain: Week 10 (Arm B n=120)(Arm A n=152)
    0.03 ( 1.02 )
    0.02 ( 1.05 )
        Chest Pain: Week 11 (Arm B n=117)(Arm A n=156)
    0.02 ( 0.96 )
    0.04 ( 1.09 )
        Chest Pain: Week 12 (Arm B n=116)(Arm A n=142)
    -0.02 ( 0.96 )
    -0.01 ( 1.02 )
        Chest Pain: Week 13 (Arm B n=108)(Arm A n=142)
    -0.05 ( 1.02 )
    0.05 ( 0.97 )
        Chest Pain: Week 14 (Arm B n=103)(Arm A n=132)
    -0.07 ( 1.12 )
    0.06 ( 1.06 )
        Chest Pain: Week 15 (Arm B n=101)(Arm A n=133)
    0.13 ( 1.16 )
    0.08 ( 0.94 )
        Chest Pain: Week 16 (Arm B n=100)(Arm A n=133)
    0.02 ( 1.08 )
    0.08 ( 1.04 )
        Chest Pain: Week 17 (Arm B n=97)(Arm A n=131)
    0.02 ( 1.08 )
    0.00 ( 1.08 )
        Chest Pain: Week 18 (Arm B n=88)(Arm A n=121)
    -0.06 ( 1.11 )
    0.12 ( 1.07 )
        Chest Pain: Week 19 (Arm B n=81)(Arm A n=122)
    -0.15 ( 1.12 )
    0.02 ( 1.01 )
        Chest Pain: Week 20 (Arm B n=71)(Arm A n=112)
    -0.02 ( 1.22 )
    -0.01 ( 1.03 )
        Chest Pain: Week 21 (Arm B n=74)(Arm A n=114)
    0.03 ( 1.28 )
    0.01 ( 1.03 )
        Chest Pain: Week 22 (Arm B n=65)(Arm A n=106)
    0.04 ( 1.21 )
    0.02 ( 1.02 )
        Chest Pain: Week 23 (Arm B n=65)(Arm A n=106)
    -0.08 ( 1.14 )
    0.04 ( 0.96 )
        Chest Pain: Week 24 (Arm B n=64)(Arm A n=106)
    -0.02 ( 1.16 )
    0.09 ( 0.99 )
        Chest Pain: Week 25 (Arm B n=60)(Arm A n=100)
    0.05 ( 1.24 )
    0.14 ( 1.03 )
        Chest Pain: Week 26 (Arm B n=55)(Arm A n=100)
    -0.05 ( 1.14 )
    0.09 ( 1.00 )
        Chest Pain: Week 27 (Arm B n=55)(Arm A n=99)
    0.04 ( 1.17 )
    0.04 ( 1.01 )
        Chest Pain: Week 28 (Arm B n=55)(Arm A n=96)
    0.24 ( 1.18 )
    0.03 ( 0.93 )
        Chest Pain: Week 29 (Arm B n=54)(Arm A n=99)
    0.06 ( 1.29 )
    0.04 ( 0.95 )
        Chest Pain: Week 30 (Arm B n=52)(Arm A n=95)
    0.01 ( 1.37 )
    0.04 ( 0.97 )
        Chest Pain: Week 31 (Arm B n=44)(Arm A n=93)
    0.02 ( 1.09 )
    0.05 ( 0.88 )
        Chest Pain: Week 32 (Arm B n=39)(Arm A n=94)
    0.21 ( 1.21 )
    -0.01 ( 0.98 )
        Chest Pain: Week 33 (Arm B n=41)(Arm A n=85)
    0.04 ( 1.17 )
    0.03 ( 0.92 )
        Chest Pain: Week 34 (Arm B n=40)(Arm A n=84)
    0.21 ( 1.27 )
    0.11 ( 0.99 )
        Chest Pain: Week 35 (Arm B n=39)(Arm A n=87)
    0.33 ( 1.30 )
    0.11 ( 0.98 )
        Chest Pain: Week 36 (Arm B n=34)(Arm A n=86)
    0.15 ( 1.07 )
    0.17 ( 1.04 )
        Chest Pain: Week 37 (Arm B n=33)(Arm A n=86)
    0.15 ( 1.21 )
    0.06 ( 0.94 )
        Chest Pain: Week 38 (Arm B n=30)(Arm A n=80)
    0.12 ( 1.16 )
    0.04 ( 1.03 )
        Chest Pain: Week 39 (Arm B n=32)(Arm A n=72)
    0.20 ( 1.23 )
    0.13 ( 1.01 )
        Chest Pain: Week 40 (Arm B n=31)(Arm A n=77)
    0.15 ( 1.31 )
    0.04 ( 0.96 )
        Chest Pain: Week 41 (Arm B n=30)(Arm A n=74)
    -0.05 ( 1.06 )
    0.09 ( 1.03 )
        Chest Pain: Week 42 (Arm B n=27)(Arm A n=73)
    -0.06 ( 1.07 )
    0.03 ( 1.02 )
        Chest Pain: Week 43 (Arm B n=23)(Arm A n=76)
    -0.22 ( 0.82 )
    0.13 ( 1.02 )
        Chest Pain: Week 44 (Arm B n=25)(Arm A n=72)
    -0.10 ( 1.29 )
    0.10 ( 1.04 )
        Chest Pain: Week 45 (Arm B n=25)(Arm A n=69)
    -0.20 ( 1.24 )
    0.03 ( 0.95 )
        Chest Pain: Week 46 (Arm B n=24)(Arm A n=67)
    -0.06 ( 1.18 )
    0.08 ( 0.99 )
        Chest Pain: Week 47 (Arm B n=23)(Arm A n=63)
    0.02 ( 1.09 )
    0.09 ( 0.91 )
        Chest Pain: Week 48 (Arm B n=25)(Arm A n=64)
    0.02 ( 1.27 )
    0.05 ( 1.00 )
        Chest Pain: Week 49 (Arm B n=23)(Arm A n=62)
    -0.09 ( 1.07 )
    0.03 ( 0.90 )
        Chest Pain: Week 50 (Arm B n=23)(Arm A n=58)
    -0.13 ( 0.99 )
    0.00 ( 1.03 )
        Chest Pain: Week 51 (Arm B n=21)(Arm A n=62)
    -0.02 ( 0.77 )
    0.12 ( 0.94 )
        Chest Pain: Week 52 (Arm B n=21)(Arm A n=55)
    0.14 ( 1.06 )
    0.00 ( 1.11 )
        Chest Pain: Week 53 (Arm B n=23)(Arm A n=54)
    0.13 ( 1.35 )
    -0.01 ( 1.06 )
        Chest Pain: Week 54 (Arm B n=22)(Arm A n=54)
    0.11 ( 1.16 )
    -0.08 ( 1.10 )
        Chest Pain: Week 55 (Arm B n=21)(Arm A n=49)
    0.12 ( 1.38 )
    0.03 ( 1.14 )
        Chest Pain: Week 56 (Arm B n=20)(Arm A n=53)
    0.13 ( 1.46 )
    0.04 ( 1.18 )
        Chest Pain: Week 57 (Arm B n=17)(Arm A n=46)
    0.12 ( 1.21 )
    -0.01 ( 1.15 )
        Chest Pain: Week 58 (Arm B n=15)(Arm A n=43)
    0.27 ( 0.98 )
    -0.12 ( 1.10 )
        Chest Pain: Week 59 (Arm B n=13)(Arm A n=40)
    0.23 ( 0.73 )
    -0.23 ( 1.01 )
        Chest Pain: Week 60 (Arm B n=11)(Arm A n=41)
    0.14 ( 0.67 )
    -0.15 ( 1.17 )
        Chest Pain: Week 61 (Arm B n=13)(Arm A n=43)
    0.23 ( 0.83 )
    0.00 ( 1.06 )
        Chest Pain: Week 62 (Arm B n=13)(Arm A n=37)
    0.46 ( 0.72 )
    -0.04 ( 1.08 )
        Chest Pain: Week 63 (Arm B n=12)(Arm A n=36)
    0.25 ( 0.75 )
    -0.06 ( 1.09 )
        Chest Pain: Week 64 (Arm B n=10)(Arm A n=35)
    0.15 ( 0.78 )
    0.09 ( 0.95 )
        Chest Pain: Week 65 (Arm B n=9)(Arm A n=33)
    0.11 ( 0.82 )
    -0.03 ( 0.99 )
        Chest Pain: Week 66 (Arm B n=6)(Arm A n=34)
    0.42 ( 0.92 )
    0.13 ( 1.05 )
        Chest Pain: Week 67 (Arm B n=7)(Arm A n=30)
    0.36 ( 0.85 )
    0.02 ( 1.00 )
        Chest Pain: Week 68 (Arm B n=6)(Arm A n=30)
    0.33 ( 0.88 )
    0.12 ( 1.18 )
        Chest Pain: Week 69 (Arm B n=7)(Arm A n=29)
    0.07 ( 0.93 )
    -0.05 ( 1.10 )
        Chest Pain: Week 70 (Arm B n=6)(Arm A n=30)
    0.25 ( 0.88 )
    0.03 ( 1.11 )
        Chest Pain: Week 71 (Arm B n=5)(Arm A n=26)
    0.30 ( 0.97 )
    0.04 ( 1.09 )
        Chest Pain: Week 72 (Arm B n=4)(Arm A n=25)
    -0.13 ( 0.25 )
    -0.22 ( 0.94 )
        Chest Pain: Week 73 (Arm B n=4)(Arm A n=24)
    0.13 ( 1.31 )
    -0.10 ( 1.01 )
        Chest Pain: Week 74 (Arm B n=4)(Arm A n=23)
    0.38 ( 1.11 )
    -0.02 ( 1.14 )
        Chest Pain: Week 75 (Arm B n=4)(Arm A n=21)
    0.38 ( 1.11 )
    -0.07 ( 1.14 )
        Chest Pain: Week 76 (Arm B n=3)(Arm A n=17)
    0.00 ( 0.50 )
    -0.06 ( 1.20 )
        Chest Pain: Week 77 (Arm B n=2)(Arm A n=17)
    -0.25 ( 0.35 )
    -0.21 ( 1.03 )
        Chest Pain: Week 78 (Arm B n=2)(Arm A n=14)
    -0.75 ( 0.35 )
    -0.25 ( 1.14 )
        Chest Pain: Week 79 (Arm B n=2)(Arm A n=14)
    0.00 ( 0.71 )
    -0.18 ( 1.20 )
        Chest Pain: Week 80 (Arm B n=2)(Arm A n=13)
    -0.25 ( 0.35 )
    -0.12 ( 0.96 )
        Chest Pain: Week 81 (Arm B n=2)(Arm A n=12)
    -0.25 ( 0.35 )
    -0.25 ( 0.89 )
        Chest Pain: Week 82 (Arm B n=2)(Arm A n=9)
    -0.75 ( 0.35 )
    0.00 ( 1.25 )
        Chest Pain: Week 83 (Arm B n=2)(Arm A n=4)
    -0.25 ( 0.35 )
    -0.50 ( 1.73 )
        Chest Pain: Week 84 (Arm B n=2)(Arm A n=5)
    0.00 ( 0.71 )
    -0.30 ( 1.57 )
        Chest Pain: Week 85 (Arm B n=1)(Arm A n=5)
    -1.00 ( 999999 )
    -0.20 ( 1.68 )
        Chest Pain: Week 86 (Arm B n=1)(Arm A n=4)
    0.00 ( 999999 )
    -0.50 ( 1.73 )
        Chest Pain: Week 87 (Arm B n=1)(Arm A n=3)
    -1.00 ( 999999 )
    0.50 ( 0.87 )
        Chest Pain: Week 88 (Arm B n=1)(Arm A n=4)
    -1.00 ( 999999 )
    0.00 ( 0.00 )
        Chest Pain: Week 89 (Arm B n=1)(Arm A n=2)
    -1.00 ( 999999 )
    0.00 ( 0.00 )
        Chest Pain: Week 90 (Arm B n=1)(Arm A n=2)
    0.00 ( 999999 )
    0.00 ( 0.00 )
        Chest Pain: Week 91 (Arm B n=1)(Arm A n=2)
    0.00 ( 999999 )
    0.00 ( 0.00 )
        Chest Pain: Week 92 (Arm B n=0)(Arm A n=2)
    999999 ( 999999 )
    0.00 ( 0.00 )
        Chest Pain: Week 93 (Arm B n=0)(Arm A n=2)
    999999 ( 999999 )
    0.00 ( 0.00 )
        Chest Pain: Week 94 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    1.00 ( 999999 )
        Chest Pain: Week 95 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    0.50 ( 999999 )
        Chest Pain: ToF Pd (Arm B n=110)(Arm A n=96)
    0.28 ( 1.06 )
    0.20 ( 0.91 )
        Chest Pain: ToLTx Dose (Arm B n=141)(Arm A n=150)
    0.17 ( 1.17 )
    0.13 ( 0.98 )
        Cough: Week 1 (Arm B n=160)(Arm A n=186)
    -0.08 ( 0.74 )
    -0.06 ( 0.89 )
        Cough: Week 2 (Arm B n=152)(Arm A n=176)
    -0.13 ( 0.73 )
    -0.08 ( 0.90 )
        Cough: Week 3 (Arm B n=151)(Arm A n=165)
    -0.05 ( 0.77 )
    -0.07 ( 0.81 )
        Cough: Week 4 (Arm B n=144)(Arm A n=160)
    -0.11 ( 0.89 )
    -0.22 ( 0.85 )
        Cough: Week 5 (Arm B n=143)(Arm A n=166)
    -0.14 ( 0.83 )
    -0.33 ( 0.89 )
        Cough: Week 6 (Arm B n=132)(Arm A n=166)
    -0.16 ( 0.85 )
    -0.33 ( 0.91 )
        Cough: Week 7 (Arm B n=132)(Arm A n=156)
    -0.22 ( 0.89 )
    -0.22 ( 0.97 )
        Cough: Week 8 (Arm B n=124)(Arm A n=157)
    -0.20 ( 0.89 )
    -0.28 ( 0.98 )
        Cough: Week 9 (Arm B n=125)(Arm A n=159)
    -0.17 ( 0.91 )
    -0.29 ( 0.97 )
        Cough: Week 10 (Arm B n=120)(Arm A n=152)
    -0.22 ( 0.95 )
    -0.35 ( 1.06 )
        Cough: Week 11 (Arm B n=117)(Arm A n=156)
    -0.21 ( 0.99 )
    -0.33 ( 1.02 )
        Cough: Week 12 (Arm B n=116)(Arm A n=142)
    -0.13 ( 1.05 )
    -0.40 ( 0.96 )
        Cough: Week 13 (Arm B n=108)(Arm A n=142)
    -0.24 ( 1.05 )
    -0.37 ( 1.04 )
        Cough: Week 14 (Arm B n=103)(Arm A n=132)
    -0.23 ( 0.98 )
    -0.34 ( 1.03 )
        Cough: Week 15 (Arm B n=101)(Arm A n=133)
    -0.11 ( 1.03 )
    -0.33 ( 1.03 )
        Cough: Week 16 (Arm B n=100)(Arm A n=133)
    -0.20 ( 1.05 )
    -0.33 ( 1.04 )
        Cough: Week 17 (Arm B n=97)(Arm A n=131)
    -0.20 ( 1.11 )
    -0.31 ( 0.99 )
        Cough: Week 18 (Arm B n=88)(Arm A n=121)
    -0.19 ( 1.12 )
    -0.31 ( 1.00 )
        Cough: Week 19 (Arm B n=81)(Arm A n=122)
    -0.25 ( 1.07 )
    -0.36 ( 1.06 )
        Cough: Week 20 (Arm B n=71)(Arm A n=112)
    -0.25 ( 1.16 )
    -0.39 ( 0.99 )
        Cough: Week 21 (Arm B n=74)(Arm A n=114)
    -0.19 ( 1.09 )
    -0.36 ( 1.07 )
        Cough: Week 22 (Arm B n=65)(Arm A n=106)
    -0.29 ( 1.11 )
    -0.41 ( 1.08 )
        Cough: Week 23 (Arm B n=65)(Arm A n=106)
    -0.34 ( 1.07 )
    -0.44 ( 1.04 )
        Cough: Week 24 (Arm B n=64)(Arm A n=106)
    -0.27 ( 0.96 )
    -0.29 ( 1.13 )
        Cough: Week 25 (Arm B n=60)(Arm A n=100)
    -0.24 ( 1.11 )
    -0.27 ( 1.10 )
        Cough: Week 26 (Arm B n=55)(Arm A n=100)
    -0.25 ( 1.16 )
    -0.22 ( 1.22 )
        Cough: Week 27 (Arm B n=55)(Arm A n=99)
    -0.19 ( 0.99 )
    -0.32 ( 1.11 )
        Cough: Week 28 (Arm B n=55)(Arm A n=96)
    -0.19 ( 1.04 )
    -0.32 ( 1.12 )
        Cough: Week 29 (Arm B n=54)(Arm A n=99)
    -0.25 ( 1.13 )
    -0.34 ( 1.11 )
        Cough: Week 30 (Arm B n=52)(Arm A n=95)
    -0.08 ( 1.12 )
    -0.34 ( 1.00 )
        Cough: Week 31 (Arm B n=44)(Arm A n=93)
    -0.13 ( 1.13 )
    -0.37 ( 0.99 )
        Cough: Week 32 (Arm B n=39)(Arm A n=94)
    0.01 ( 1.09 )
    -0.45 ( 0.94 )
        Cough: Week 33 (Arm B n=41)(Arm A n=85)
    0.05 ( 1.17 )
    -0.44 ( 0.99 )
        Cough: Week 34 (Arm B n=40)(Arm A n=84)
    -0.10 ( 1.09 )
    -0.29 ( 1.02 )
        Cough: Week 35 (Arm B n=39)(Arm A n=87)
    -0.27 ( 1.05 )
    -0.32 ( 0.99 )
        Cough: Week 36 (Arm B n=34)(Arm A n=86)
    0.01 ( 1.10 )
    -0.31 ( 0.99 )
        Cough: Week 37 (Arm B n=33)(Arm A n=86)
    -0.11 ( 1.16 )
    -0.37 ( 1.01 )
        Cough: Week 38 (Arm B n=30)(Arm A n=80)
    0.02 ( 1.03 )
    -0.31 ( 1.03 )
        Cough: Week 39 (Arm B n=32)(Arm A n=72)
    0.02 ( 1.19 )
    -0.33 ( 0.98 )
        Cough: Week 40 (Arm B n=31)(Arm A n=77)
    -0.10 ( 1.15 )
    -0.35 ( 1.07 )
        Cough: Week 41 (Arm B n=30)(Arm A n=74)
    -0.27 ( 1.10 )
    -0.30 ( 1.09 )
        Cough: Week 42 (Arm B n=27)(Arm A n=73)
    -0.31 ( 1.04 )
    -0.31 ( 1.04 )
        Cough: Week 43 (Arm B n=23)(Arm A n=76)
    -0.20 ( 1.04 )
    -0.37 ( 0.98 )
        Cough: Week 44 (Arm B n=25)(Arm A n=72)
    0.00 ( 1.04 )
    -0.36 ( 1.03 )
        Cough: Week 45 (Arm B n=25)(Arm A n=69)
    -0.18 ( 1.14 )
    -0.41 ( 1.04 )
        Cough: Week 46 (Arm B n=24)(Arm A n=67)
    -0.25 ( 1.04 )
    -0.34 ( 1.17 )
        Cough: Week 47 (Arm B n=23)(Arm A n=63)
    -0.43 ( 1.09 )
    -0.29 ( 1.17 )
        Cough: Week 48 (Arm B n=25)(Arm A n=64)
    -0.26 ( 1.16 )
    -0.38 ( 1.08 )
        Cough: Week 49 (Arm B n=23)(Arm A n=62)
    -0.50 ( 1.07 )
    -0.40 ( 1.10 )
        Cough: Week 50 (Arm B n=23)(Arm A n=58)
    -0.37 ( 0.84 )
    -0.40 ( 1.06 )
        Cough: Week 51 (Arm B n=21)(Arm A n=62)
    -0.45 ( 1.16 )
    -0.15 ( 1.10 )
        Cough: Week 52 (Arm B n=21)(Arm A n=55)
    -0.29 ( 1.07 )
    -0.10 ( 1.17 )
        Cough: Week 53 (Arm B n=23)(Arm A n=54)
    -0.24 ( 1.21 )
    -0.13 ( 1.17 )
        Cough: Week 54 (Arm B n=22)(Arm A n=54)
    -0.27 ( 1.10 )
    -0.16 ( 1.15 )
        Cough: Week 55 (Arm B n=21)(Arm A n=49)
    -0.10 ( 1.15 )
    -0.35 ( 1.13 )
        Cough: Week 56 (Arm B n=20)(Arm A n=53)
    -0.30 ( 1.14 )
    -0.26 ( 1.17 )
        Cough: Week 57 (Arm B n=17)(Arm A n=46)
    -0.41 ( 0.92 )
    -0.25 ( 1.10 )
        Cough: Week 58 (Arm B n=15)(Arm A n=43)
    -0.17 ( 1.05 )
    -0.45 ( 0.96 )
        Cough: Week 59 (Arm B n=13)(Arm A n=40)
    -0.31 ( 0.93 )
    -0.50 ( 1.02 )
        Cough: Week 60 (Arm B n=11)(Arm A n=41)
    -0.55 ( 1.04 )
    -0.52 ( 1.03 )
        Cough: Week 61 (Arm B n=13)(Arm A n=43)
    -0.23 ( 1.15 )
    -0.38 ( 1.07 )
        Cough: Week 62 (Arm B n=13)(Arm A n=37)
    0.04 ( 1.03 )
    -0.53 ( 1.15 )
        Cough: Week 63 (Arm B n=12)(Arm A n=36)
    -0.29 ( 1.18 )
    -0.57 ( 1.10 )
        Cough: Week 64 (Arm B n=10)(Arm A n=35)
    -0.45 ( 1.04 )
    -0.49 ( 1.01 )
        Cough: Week 65 (Arm B n=9)(Arm A n=33)
    -0.61 ( 0.96 )
    -0.39 ( 0.94 )
        Cough: Week 66 (Arm B n=6)(Arm A n=34)
    -0.17 ( 0.82 )
    -0.43 ( 1.18 )
        Cough: Week 67 (Arm B n=7)(Arm A n=30)
    -0.64 ( 1.07 )
    -0.47 ( 0.84 )
        Cough: Week 68 (Arm B n=6)(Arm A n=30)
    -0.75 ( 0.88 )
    -0.35 ( 1.04 )
        Cough: Week 69 (Arm B n=7)(Arm A n=29)
    -0.57 ( 1.10 )
    -0.53 ( 0.90 )
        Cough: Week 70 (Arm B n=6)(Arm A n=30)
    -0.83 ( 0.93 )
    -0.43 ( 0.98 )
        Cough: Week 71 (Arm B n=5)(Arm A n=26)
    -0.90 ( 0.89 )
    -0.56 ( 1.04 )
        Cough: Week 72 (Arm B n=4)(Arm A n=25)
    -1.25 ( 0.50 )
    -0.72 ( 1.15 )
        Cough: Week 73 (Arm B n=4)(Arm A n=24)
    -0.63 ( 1.11 )
    -0.77 ( 1.00 )
        Cough: Week 74 (Arm B n=4)(Arm A n=23)
    -0.63 ( 1.11 )
    -0.54 ( 0.94 )
        Cough: Week 75 (Arm B n=4)(Arm A n=21)
    -0.63 ( 1.11 )
    -0.67 ( 1.00 )
        Cough: Week 76 (Arm B n=3)(Arm A n=17)
    -1.00 ( 1.00 )
    -0.65 ( 1.22 )
        Cough: Week 77 (Arm B n=2)(Arm A n=17)
    -0.50 ( 0.71 )
    -0.82 ( 1.21 )
        Cough: Week 78 (Arm B n=2)(Arm A n=14)
    -1.00 ( 0.00 )
    -0.57 ( 1.04 )
        Cough: Week 79 (Arm B n=2)(Arm A n=14)
    -0.25 ( 0.35 )
    -0.64 ( 1.23 )
        Cough: Week 80 (Arm B n=2)(Arm A n=13)
    -0.50 ( 0.71 )
    -1.04 ( 1.11 )
        Cough: Week 81 (Arm B n=2)(Arm A n=12)
    -0.50 ( 0.71 )
    -0.79 ( 1.05 )
        Cough: Week 82 (Arm B n=2)(Arm A n=9)
    -0.50 ( 0.71 )
    -0.89 ( 1.27 )
        Cough: Week 83 (Arm B n=2)(Arm A n=4)
    -1.00 ( 0.00 )
    0.13 ( 1.03 )
        Cough: Week 84 (Arm B n=2)(Arm A n=5)
    -0.50 ( 0.71 )
    -0.20 ( 1.04 )
        Cough: Week 85 (Arm B n=1)(Arm A n=5)
    0.00 ( 999999 )
    0.00 ( 0.87 )
        Cough: Week 86 (Arm B n=1)(Arm A n=4)
    0.00 ( 999999 )
    -0.38 ( 0.48 )
        Cough: Week 87 (Arm B n=1)(Arm A n=3)
    0.00 ( 999999 )
    -0.83 ( 0.58 )
        Cough: Week 88 (Arm B n=1)(Arm A n=4)
    0.00 ( 999999 )
    -0.88 ( 0.48 )
        Cough: Week 89 (Arm B n=1)(Arm A n=2)
    0.00 ( 999999 )
    0.00 ( 0.71 )
        Cough: Week 90 (Arm B n=1)(Arm A n=2)
    0.00 ( 999999 )
    0.25 ( 1.06 )
        Cough: Week 91 (Arm B n=1)(Arm A n=2)
    0.00 ( 999999 )
    -0.50 ( 0.00 )
        Cough: Week 92 (Arm B n=0)(Arm A n=2)
    999999 ( 999999 )
    0.50 ( 0.71 )
        Cough: Week 93 (Arm B n=0)(Arm A n=2)
    999999 ( 999999 )
    0.50 ( 0.71 )
        Cough: Week 94 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    0.50 ( 999999 )
        Cough: Week 95 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    0.00 ( 999999 )
        Cough: ToF Pd (Arm B n=110)(Arm A n=96)
    -0.08 ( 1.12 )
    -0.45 ( 0.93 )
        Cough: ToL Tx Dose (Arm B n=141)(Arm A n=150)
    -0.15 ( 0.95 )
    -0.29 ( 0.91 )
        Dyspnoea: Week 1 (Arm B n=160)(Arm A n=186)
    0.20 ( 0.82 )
    0.16 ( 0.81 )
        Dyspnoea: Week 2 (Arm B n=152)(Arm A n=176)
    0.11 ( 0.76 )
    0.15 ( 0.82 )
        Dyspnoea: Week 3 (Arm B n=151)(Arm A n=165)
    0.10 ( 0.71 )
    0.12 ( 0.70 )
        Dyspnoea: Week 4 (Arm B n=144)(Arm A n=160)
    0.21 ( 0.84 )
    0.17 ( 0.95 )
        Dyspnoea: Week 5 (Arm B n=143)(Arm A n=166)
    0.22 ( 0.82 )
    0.17 ( 0.91 )
        Dyspnoea: Week 6 (Arm B n=132)(Arm A n=166)
    0.23 ( 0.82 )
    0.16 ( 0.95 )
        Dyspnoea: Week 7 (Arm B n=132)(Arm A n=156)
    0.30 ( 0.93 )
    0.25 ( 0.92 )
        Dyspnoea: Week 8 (Arm B n=124)(Arm A n=157)
    0.35 ( 0.87 )
    0.24 ( 0.96 )
        Dyspnoea: Week 9 (Arm B n=125)(Arm A n=159)
    0.34 ( 0.89 )
    0.17 ( 0.91 )
        Dyspnoea: Week 10 (Arm B n=120)(Arm A n=152)
    0.46 ( 0.93 )
    0.16 ( 0.92 )
        Dyspnoea: Week 11 (Arm B n=117)(Arm A n=156)
    0.39 ( 1.01 )
    0.26 ( 0.96 )
        Dyspnoea: Week 12 (Arm B n=116)(Arm A n=142)
    0.38 ( 0.96 )
    0.22 ( 0.90 )
        Dyspnoea: Week 13 (Arm B n=108)(Arm A n=142)
    0.34 ( 0.96 )
    0.30 ( 1.02 )
        Dyspnoea: Week 14 (Arm B n=103)(Arm A n=132)
    0.44 ( 0.95 )
    0.22 ( 0.99 )
        Dyspnoea: Week 15 (Arm B n=101)(Arm A n=133)
    0.45 ( 0.94 )
    0.19 ( 0.95 )
        Dyspnoea: Week 16 (Arm B n=100)(Arm A n=133)
    0.37 ( 1.06 )
    0.26 ( 1.02 )
        Dyspnoea: Week 17 (Arm B n=97)(Arm A n=131)
    0.35 ( 1.04 )
    0.15 ( 1.00 )
        Dyspnoea: Week 18 (Arm B n=88)(Arm A n=121)
    0.35 ( 0.99 )
    0.22 ( 0.99 )
        Dyspnoea: Week 19 (Arm B n=81)(Arm A n=122)
    0.30 ( 1.02 )
    0.22 ( 0.97 )
        Dyspnoea: Week 20 (Arm B n=71)(Arm A n=112)
    0.30 ( 1.09 )
    0.27 ( 1.06 )
        Dyspnoea: Week 21 (Arm B n=74)(Arm A n=114)
    0.22 ( 1.03 )
    0.22 ( 1.05 )
        Dyspnoea: Week 22 (Arm B n=65)(Arm A n=106)
    0.16 ( 1.10 )
    0.28 ( 1.03 )
        Dyspnoea: Week 23 (Arm B n=65)(Arm A n=106)
    0.24 ( 1.05 )
    0.22 ( 1.03 )
        Dyspnoea: Week 24 (Arm B n=64)(Arm A n=106)
    0.30 ( 0.98 )
    0.24 ( 0.99 )
        Dyspnoea: Week 25 (Arm B n=60)(Arm A n=100)
    0.50 ( 1.05 )
    0.28 ( 0.99 )
        Dyspnoea: Week 26 (Arm B n=55)(Arm A n=100)
    0.30 ( 1.05 )
    0.24 ( 1.04 )
        Dyspnoea: Week 27 (Arm B n=55)(Arm A n=99)
    0.43 ( 1.17 )
    0.24 ( 1.06 )
        Dyspnoea: Week 28 (Arm B n=55)(Arm A n=96)
    0.46 ( 1.02 )
    0.25 ( 0.97 )
        Dyspnoea: Week 29 (Arm B n=54)(Arm A n=99)
    0.43 ( 1.06 )
    0.20 ( 1.01 )
        Dyspnoea: Week 30 (Arm B n=52)(Arm A n=95)
    0.45 ( 1.08 )
    0.21 ( 0.99 )
        Dyspnoea: Week 31 (Arm B n=44)(Arm A n=93)
    0.35 ( 1.03 )
    0.15 ( 0.99 )
        Dyspnoea: Week 32 (Arm B n=39)(Arm A n=94)
    0.48 ( 1.03 )
    0.16 ( 1.01 )
        Dyspnoea: Week 33 (Arm B n=41)(Arm A n=85)
    0.36 ( 0.96 )
    0.17 ( 0.95 )
        Dyspnoea: Week 34 (Arm B n=40)(Arm A n=84)
    0.47 ( 1.15 )
    0.24 ( 1.04 )
        Dyspnoea: Week 35 (Arm B n=39)(Arm A n=87)
    0.42 ( 1.00 )
    0.23 ( 1.03 )
        Dyspnoea: Week 36 (Arm B n=34)(Arm A n=86)
    0.59 ( 1.06 )
    0.22 ( 1.02 )
        Dyspnoea: Week 37 (Arm B n=33)(Arm A n=86)
    0.53 ( 1.17 )
    0.24 ( 1.03 )
        Dyspnoea: Week 38 (Arm B n=30)(Arm A n=80)
    0.59 ( 1.06 )
    0.22 ( 1.07 )
        Dyspnoea: Week 39 (Arm B n=32)(Arm A n=72)
    0.65 ( 1.04 )
    0.19 ( 1.01 )
        Dyspnoea: Week 40 (Arm B n=31)(Arm A n=77)
    0.62 ( 1.02 )
    0.19 ( 0.95 )
        Dyspnoea: Week 41 (Arm B n=30)(Arm A n=74)
    0.63 ( 1.01 )
    0.16 ( 0.95 )
        Dyspnoea: Week 42 (Arm B n=27)(Arm A n=73)
    0.50 ( 1.01 )
    0.17 ( 0.92 )
        Dyspnoea: Week 43 (Arm B n=23)(Arm A n=76)
    0.32 ( 0.89 )
    0.22 ( 0.90 )
        Dyspnoea: Week 44 (Arm B n=25)(Arm A n=72)
    0.58 ( 0.83 )
    0.23 ( 0.92 )
        Dyspnoea: Week 45 (Arm B n=25)(Arm A n=69)
    0.49 ( 0.96 )
    0.21 ( 0.90 )
        Dyspnoea: Week 46 (Arm B n=24)(Arm A n=67)
    0.55 ( 1.02 )
    0.23 ( 0.89 )
        Dyspnoea: Week 47 (Arm B n=23)(Arm A n=63)
    0.53 ( 1.09 )
    0.14 ( 0.90 )
        Dyspnoea: Week 48 (Arm B n=25)(Arm A n=64)
    0.55 ( 0.96 )
    0.14 ( 0.85 )
        Dyspnoea: Week 49 (Arm B n=23)(Arm A n=62)
    0.63 ( 1.04 )
    0.16 ( 0.90 )
        Dyspnoea: Week 50 (Arm B n=23)(Arm A n=58)
    0.52 ( 0.98 )
    0.24 ( 0.94 )
        Dyspnoea: Week 51 (Arm B n=21)(Arm A n=62)
    0.67 ( 1.04 )
    0.30 ( 0.97 )
        Dyspnoea: Week 52 (Arm B n=21)(Arm A n=55)
    0.72 ( 1.02 )
    0.27 ( 1.02 )
        Dyspnoea: Week 53 (Arm B n=23)(Arm A n=54)
    0.81 ( 1.06 )
    0.22 ( 0.95 )
        Dyspnoea: Week 54 (Arm B n=22)(Arm A n=54)
    0.82 ( 1.06 )
    0.23 ( 0.95 )
        Dyspnoea: Week 55 (Arm B n=21)(Arm A n=49)
    0.77 ( 1.17 )
    0.16 ( 0.99 )
        Dyspnoea: Week 56 (Arm B n=20)(Arm A n=53)
    0.84 ( 1.15 )
    0.18 ( 0.95 )
        Dyspnoea: Week 57 (Arm B n=17)(Arm A n=46)
    0.68 ( 1.16 )
    0.11 ( 0.91 )
        Dyspnoea: Week 58 (Arm B n=15)(Arm A n=43)
    0.77 ( 1.06 )
    0.16 ( 0.86 )
        Dyspnoea: Week 59 (Arm B n=13)(Arm A n=40)
    0.66 ( 0.90 )
    0.07 ( 0.85 )
        Dyspnoea: Week 60 (Arm B n=11)(Arm A n=41)
    0.73 ( 0.96 )
    0.27 ( 0.94 )
        Dyspnoea: Week 61 (Arm B n13=)(Arm A n=43)
    0.85 ( 1.04 )
    0.23 ( 0.90 )
        Dyspnoea: Week 62 (Arm B n=13)(Arm A n=37)
    0.95 ( 1.05 )
    0.16 ( 0.92 )
        Dyspnoea: Week 63 (Arm B n=12)(Arm A n=36)
    0.67 ( 1.01 )
    0.27 ( 0.95 )
        Dyspnoea: Week 64 (Arm B n=10)(Arm A n=35)
    0.46 ( 0.78 )
    0.14 ( 0.93 )
        Dyspnoea: Week 65 (Arm B n=9)(Arm A n=33)
    0.40 ( 0.66 )
    0.12 ( 0.95 )
        Dyspnoea: Week 66 (Arm B n=6)(Arm A n=34)
    0.67 ( 0.74 )
    0.16 ( 0.94 )
        Dyspnoea: Week 67 (Arm B n=7)(Arm A n=30)
    0.37 ( 0.76 )
    0.26 ( 1.01 )
        Dyspnoea: Week 68 (Arm B n=6)(Arm A n=30)
    0.47 ( 0.80 )
    0.25 ( 1.03 )
        Dyspnoea: Week 69 (Arm B n=7)(Arm A n=29)
    0.43 ( 0.80 )
    0.16 ( 1.11 )
        Dyspnoea: Week 70 (Arm B n=6)(Arm A n=30)
    0.33 ( 0.83 )
    0.07 ( 0.89 )
        Dyspnoea: Week 71 (Arm B n=5)(Arm A n=26)
    0.40 ( 0.91 )
    0.13 ( 0.89 )
        Dyspnoea: Week 72 (Arm B n=4)(Arm A n=25)
    -0.05 ( 0.25 )
    0.06 ( 0.91 )
        Dyspnoea: Week 73 (Arm B n=4)(Arm A n=24)
    0.45 ( 1.04 )
    0.09 ( 0.99 )
        Dyspnoea: Week 74 (Arm B n=4)(Arm A n=23)
    0.50 ( 1.01 )
    0.27 ( 1.19 )
        Dyspnoea: Week 75 (Arm B n=4)(Arm A n=21)
    0.55 ( 0.97 )
    0.45 ( 1.31 )
        Dyspnoea: Week 76 (Arm B n=3)(Arm A n=17)
    -0.07 ( 0.12 )
    0.02 ( 1.10 )
        Dyspnoea: Week 77 (Arm B n=2)(Arm A n=17)
    0.00 ( 0.00 )
    0.09 ( 1.17 )
        Dyspnoea: Week 78 (Arm B n=2)(Arm A n=14)
    0.00 ( 0.00 )
    0.03 ( 1.19 )
        Dyspnoea: Week 79 (Arm B n=2)(Arm A n=14)
    0.00 ( 0.00 )
    0.19 ( 1.18 )
        Dyspnoea: Week 80 (Arm B n=2)(Arm A n=13)
    0.10 ( 0.14 )
    -0.26 ( 0.80 )
        Dyspnoea: Week 81 (Arm B n=2)(Arm A n=12)
    0.10 ( 0.14 )
    -0.17 ( 1.15 )
        Dyspnoea: Week 82 (Arm B n=2)(Arm A n=9)
    0.00 ( 0.00 )
    0.18 ( 1.54 )
        Dyspnoea: Week 83 (Arm B n=2)(Arm A n=4)
    0.00 ( 0.00 )
    0.45 ( 1.22 )
        Dyspnoea: Week 84 (Arm B n=2)(Arm A n=5)
    0.00 ( 0.00 )
    0.60 ( 1.10 )
        Dyspnoea: Week 85 (Arm B n=1)(Arm A n=5)
    0.20 ( 999999 )
    0.32 ( 1.53 )
        Dyspnoea: Week 86 (Arm B n=1)(Arm A n=4)
    0.00 ( 999999 )
    -0.15 ( 0.34 )
        Dyspnoea: Week 87 (Arm B n=1)(Arm A n=3)
    0.20 ( 999999 )
    -0.47 ( 0.23 )
        Dyspnoea: Week 88 (Arm B n=1)(Arm A n=4)
    0.20 ( 999999 )
    -0.70 ( 0.20 )
        Dyspnoea: Week 89 (Arm B n=1)(Arm A n=2)
    0.20 ( 999999 )
    -0.20 ( 0.57 )
        Dyspnoea: Week 90 (Arm B n=1)(Arm A n=2)
    0.20 ( 999999 )
    -0.50 ( 0.14 )
        Dyspnoea: Week 91 (Arm B n=1)(Arm A n=2)
    0.00 ( 999999 )
    -0.50 ( 0.14 )
        Dyspnoea: Week 92 (Arm B n=0)(Arm A n=2)
    999999 ( 999999 )
    -0.70 ( 0.14 )
        Dyspnoea: Week 93 (Arm B n=0)(Arm A n=2)
    999999 ( 999999 )
    -0.40 ( 0.28 )
        Dyspnoea: Week 94 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    -0.80 ( 999999 )
        Dyspnoea: Week 95 (Arm B n=0)(Arm A n=1)
    999999 ( 999999 )
    -1.00 ( 999999 )
        Dyspnoea: ToF Pd (Arm B n=110)(Arm A n=96)
    0.58 ( 0.99 )
    0.40 ( 1.06 )
        Dyspnoea: ToL Tx Dose (Arm B n=141)(Arm A n=150)
    0.47 ( 0.95 )
    0.18 ( 0.94 )
    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) [1]
    End point description
    Minimum observed serum atezolizumab concentration (Cmin) prior to infusion at selected cycles (Arm A).
    End point type
    Secondary
    End point timeframe
    Predose (Prd; 0 hour [h]) on D1 of Cy 2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle (up to approximately 25 months)
    Notes
    [1] - 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 + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    247
    Units: μg/mL
    arithmetic mean (standard deviation)
        Cy2D1 (n=247)
    69.8 ( 32.3 )
        Cy3D1 (n=228)
    115 ( 51.5 )
        Cy4D1 (n=213)
    151 ( 69.9 )
        Cy8D1 (n=145)
    221 ( 101 )
        Cy16D1 (n=76)
    234 ( 86.7 )
        Cy24D1 (n=13)
    257 ( 95.1 )
        Treatment Discontinuation Visit (n=131)
    129 ( 93.1 )
        Day 120 Post Last Dose (n=55)
    13.4 ( 19.4 )
    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) [2]
    End point description
    Maximum observed serum atezolizumab concentration (Cmax) after infusion (Arm A)
    End point type
    Secondary
    End point timeframe
    Day 1 of Cycle 1 (Cycle length=21 days)
    Notes
    [2] - 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 + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    273
    Units: μg/mL
    arithmetic mean (standard deviation)
        Cy1D1
    403 ( 118 )
    No statistical analyses for this end point

    Secondary: Plasma Concentrations for Carboplatin in Arm A(Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)

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    End point title
    		 Plasma Concentrations for Carboplatin in Arm A(Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) [3]
    End point description
    Note: 999999 = not available.
    End point type
    Secondary
    End point timeframe
    Prd (0 h), 5-10 minutes (mins) before end of carboplatin infusion (infusion duration=1-2 h), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)
    Notes
    [3] - 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 + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    27
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cy1D1 Predose
    999999 ( 999999 )
        Cy1D1 Before End of Infusion
    14900 ( 4260 )
        Cy1D1 Post Infusion
    12800 ( 4470 )
        Cy3D1 Predose
    220 ( 83.8 )
        Cy3D1 Before End of Infusion
    17900 ( 4390 )
        Cy3D1 Post Infusion
    13900 ( 4080 )
    No statistical analyses for this end point

    Secondary: Plasma Concentrations for Cisplatin in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)

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    End point title
    		 Plasma Concentrations for Cisplatin in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) [4]
    End point description
    Note: 999999=not available.
    End point type
    Secondary
    End point timeframe
    Prd (0 h), 5-10 mins before end of cisplatin infusion (infusion duration=30-60 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)
    Notes
    [4] - 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 + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    10
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cy1D1 Predose
    999999 ( 999999 )
        Cy1D1 Before End of Infusion
    3630 ( 589 )
        Cy1D1 Post Infusion
    2400 ( 360 )
        Cy3D1 Predose
    290 ( 86.1 )
        Cy3D1 Before End of Infusion
    3020 ( 968 )
        Cy3D1 Post Infusion
    2740 ( 543 )
    No statistical analyses for this end point

    Secondary: Plasma Concentrations for Pemetrexed in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)

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    End point title
    		 Plasma Concentrations for Pemetrexed in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) [5]
    End point description
    Note: 999999=not available.
    End point type
    Secondary
    End point timeframe
    Prd (0 h), 5-10 mins before end of pemetrexed infusion (infusion duration=10 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)
    Notes
    [5] - 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 + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    36
    Units: ng/mL
    arithmetic mean (standard deviation)
        Cy1D1 Predose
    999999 ( 999999 )
        Cy1D1 Before End of Infusion
    86500 ( 41600 )
        Cy1D1 Post Infusion
    43600 ( 15800 )
        Cy3D1 Predose
    1.83 ( 0.681 )
        Cy3D1 Before End of Infusion
    79400 ( 44400 )
        Cy3D1 Post Infusion
    50100 ( 26100 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) of Atezolizumab

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    End point title
    		 Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) of Atezolizumab [6]
    End point description
    Baseline prevalence and post-baseline incidence of anti-drug antibodies (ADA) to Atezolizumab in the Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)
    End point type
    Secondary
    End point timeframe
    Prd (0 h) on D1 of Cy1,2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle, at treatment discontinuation & then every 30 days (up to 120 days) after last dose of atezolizumab (up to app 25 months)
    Notes
    [6] - 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 + Carboplatin or Cisplatin + Pemetrexed
    Number of subjects analysed
    291
    Units: Percentage of Participants
    number (not applicable)
        Baseline Evaluable Participants
    1.8
        Post-Baseline Evaluable Participants
    35.4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first study drug to the data cutoff date: 13 December 2022 (up to approximately 80 months).
    Adverse event reporting additional description
    Adverse events reported based on safety population, which included participants who received any amount of any component of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.1
    Reporting groups
    Reporting group title
    Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed
    Reporting group description
    		 Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.

    Reporting group title
    Arm B (Carboplatin or Cisplatin + Pemetrexed)
    Reporting group description
    		 Participants received IV infusion of 500 mg/m^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who do not experience disease progression during the induction phase will begin maintenance therapy. Participants will receive IV infusion of 500 mg/m^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period.

    Serious adverse events
    		 Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed Arm B (Carboplatin or Cisplatin + Pemetrexed)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    149 / 291 (51.20%)
    91 / 274 (33.21%)
         number of deaths (all causes)
    199
    199
         number of deaths resulting from adverse events
    11
    8
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    TUMOUR EMBOLISM
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    ADENOCARCINOMA GASTRIC
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CANCER PAIN
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HISTIOCYTIC NECROTISING LYMPHADENITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    METASTASES TO CENTRAL NERVOUS SYSTEM
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PROSTATE CANCER RECURRENT
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    AORTIC EMBOLUS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EMBOLISM
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERTENSION
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIPHERAL ARTERY THROMBOSIS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIPHERAL ISCHAEMIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    THROMBOPHLEBITIS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VASCULITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    FATIGUE
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    2 / 291 (0.69%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    1 / 2
    1 / 1
    CHEST PAIN
         subjects affected / exposed
    0 / 291 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ASTHENIA
         subjects affected / exposed
    5 / 291 (1.72%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    3 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GAIT DISTURBANCE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    3 / 291 (1.03%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    2 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFLAMMATION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MALAISE
         subjects affected / exposed
    1 / 291 (0.34%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NON-CARDIAC CHEST PAIN
         subjects affected / exposed
    0 / 291 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PAIN
         subjects affected / exposed
    0 / 291 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PYREXIA
         subjects affected / exposed
    12 / 291 (4.12%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    6 / 12
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DISEASE SUSCEPTIBILITY
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    HYPERSENSITIVITY
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CYTOKINE RELEASE SYNDROME
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    BENIGN PROSTATIC HYPERPLASIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    PLEURAL EFFUSION
         subjects affected / exposed
    1 / 291 (0.34%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATELECTASIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHIAL HYPERREACTIVITY
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    2 / 291 (0.69%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DYSPNOEA
         subjects affected / exposed
    2 / 291 (0.69%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    EPISTAXIS
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HAEMOPTYSIS
         subjects affected / exposed
    2 / 291 (0.69%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    HYPERVENTILATION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTERSTITIAL LUNG DISEASE
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    ORGANISING PNEUMONIA
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PHARYNGEAL INFLAMMATION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    4 / 291 (1.37%)
    4 / 274 (1.46%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 4
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    PULMONARY HAEMORRHAGE
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    PNEUMONITIS
         subjects affected / exposed
    9 / 291 (3.09%)
    4 / 274 (1.46%)
         occurrences causally related to treatment / all
    9 / 9
    4 / 4
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CATATONIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COMPLETED SUICIDE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Product issues
    DEVICE MALFUNCTION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    3 / 291 (1.03%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    3 / 291 (1.03%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CREATININE RENAL CLEARANCE DECREASED
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    0 / 291 (0.00%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    0 / 0
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLATELET COUNT DECREASED
         subjects affected / exposed
    1 / 291 (0.34%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    WEIGHT DECREASED
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTENTIONAL OVERDOSE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUMBAR VERTEBRAL FRACTURE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SKIN INJURY
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STAB WOUND
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUBDURAL HAEMATOMA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    TOXICITY TO VARIOUS AGENTS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FALL
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    TACHYCARDIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUPRAVENTRICULAR TACHYCARDIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STRESS CARDIOMYOPATHY
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYOCARDITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CARDIAC FAILURE ACUTE
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    CARDIAC FAILURE
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ACUTE MYOCARDIAL INFARCTION
         subjects affected / exposed
    1 / 291 (0.34%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Nervous system disorders
    APHASIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRAIN OEDEMA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CAROTID ARTERY OCCLUSION
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CAROTID ARTERY STENOSIS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBRAL HAEMORRHAGE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBRAL INFARCTION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CEREBROVASCULAR ACCIDENT
         subjects affected / exposed
    4 / 291 (1.37%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    1 / 1
    HEADACHE
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LETHARGY
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    SYNCOPE
         subjects affected / exposed
    0 / 291 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRANSIENT ISCHAEMIC ATTACK
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ATAXIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHANGE IN SEIZURE PRESENTATION
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    FEBRILE BONE MARROW APLASIA
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    12 / 291 (4.12%)
    5 / 274 (1.82%)
         occurrences causally related to treatment / all
    12 / 12
    3 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    11 / 291 (3.78%)
    4 / 274 (1.46%)
         occurrences causally related to treatment / all
    14 / 15
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PANCYTOPENIA
         subjects affected / exposed
    4 / 291 (1.37%)
    4 / 274 (1.46%)
         occurrences causally related to treatment / all
    4 / 4
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    NEUTROPENIA
         subjects affected / exposed
    3 / 291 (1.03%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    3 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LEUKOPENIA
         subjects affected / exposed
    2 / 291 (0.69%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ANAEMIA
         subjects affected / exposed
    11 / 291 (3.78%)
    7 / 274 (2.55%)
         occurrences causally related to treatment / all
    13 / 14
    9 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYELOSUPPRESSION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    CATARACT
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    PANCREATITIS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PROCTITIS ULCERATIVE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    OESOPHAGITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NAUSEA
         subjects affected / exposed
    2 / 291 (0.69%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    1 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTESTINAL OBSTRUCTION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INGUINAL HERNIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROINTESTINAL DISORDER
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTRIC PERFORATION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENTEROCOLITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIVERTICULUM INTESTINAL HAEMORRHAGIC
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    9 / 291 (3.09%)
    3 / 274 (1.09%)
         occurrences causally related to treatment / all
    8 / 9
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COLITIS
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    AUTOIMMUNE COLITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    4 / 291 (1.37%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    3 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SMALL INTESTINAL PERFORATION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    VOMITING
         subjects affected / exposed
    6 / 291 (2.06%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    4 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    STOMATITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    CHOLANGITIS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    AUTOIMMUNE HEPATITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEPATOTOXICITY
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    HEPATITIS ACUTE
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEPATITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DRUG-INDUCED LIVER INJURY
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BILIARY OBSTRUCTION
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CONGESTIVE HEPATOPATHY
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    DERMATITIS
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RASH
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RASH MACULO-PAPULAR
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    3 / 291 (1.03%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    CHRONIC KIDNEY DISEASE
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEPHRITIS ALLERGIC
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    1 / 291 (0.34%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    RENAL IMPAIRMENT
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TUBULOINTERSTITIAL NEPHRITIS
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GLYCOSURIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    HYPOTHYROIDISM
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    BACK PAIN
         subjects affected / exposed
    0 / 291 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BONE PAIN
         subjects affected / exposed
    0 / 291 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    FRACTURE PAIN
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MUSCULOSKELETAL CHEST PAIN
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYALGIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NECK PAIN
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    BACTERAEMIA
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFECTIOUS PLEURAL EFFUSION
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    H3N2 INFLUENZA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    ESCHERICHIA URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ERYSIPELAS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENCEPHALITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIVERTICULITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CELLULITIS
         subjects affected / exposed
    3 / 291 (1.03%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CAMPYLOBACTER GASTROENTERITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHOPULMONARY ASPERGILLOSIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFLUENZA
         subjects affected / exposed
    3 / 291 (1.03%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MENINGITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUTROPENIC SEPSIS
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    OESOPHAGEAL CANDIDIASIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PERIPHERAL NERVE INFECTION
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PHARYNGITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    17 / 291 (5.84%)
    16 / 274 (5.84%)
         occurrences causally related to treatment / all
    6 / 18
    5 / 17
         deaths causally related to treatment / all
    1 / 2
    3 / 4
    UROSEPSIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    6 / 291 (2.06%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    2 / 6
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TRACHEITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SOFT TISSUE INFECTION
         subjects affected / exposed
    1 / 291 (0.34%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    4 / 291 (1.37%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    6 / 291 (2.06%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    1 / 9
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY SEPSIS
         subjects affected / exposed
    2 / 291 (0.69%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LOWER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 291 (0.00%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    2 / 291 (0.69%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROENTERITIS CLOSTRIDIAL
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LARYNGOPHARYNGITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VASCULAR ACCESS SITE CELLULITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    1 / 291 (0.34%)
    2 / 274 (0.73%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    2 / 291 (0.69%)
    4 / 274 (1.46%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DIABETES MELLITUS INADEQUATE CONTROL
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GOUT
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERCALCAEMIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERKALAEMIA
         subjects affected / exposed
    0 / 291 (0.00%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPOMAGNESAEMIA
         subjects affected / exposed
    1 / 291 (0.34%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPONATRAEMIA
         subjects affected / exposed
    2 / 291 (0.69%)
    1 / 274 (0.36%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HYPERGLYCAEMIA
         subjects affected / exposed
    3 / 291 (1.03%)
    0 / 274 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed Arm B (Carboplatin or Cisplatin + Pemetrexed)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    275 / 291 (94.50%)
    255 / 274 (93.07%)
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    17 / 291 (5.84%)
    7 / 274 (2.55%)
         occurrences all number
    31
    9
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    59 / 291 (20.27%)
    37 / 274 (13.50%)
         occurrences all number
    89
    50
    ASTHENIA
         subjects affected / exposed
    79 / 291 (27.15%)
    54 / 274 (19.71%)
         occurrences all number
    118
    81
    CHEST PAIN
         subjects affected / exposed
    22 / 291 (7.56%)
    18 / 274 (6.57%)
         occurrences all number
    25
    18
    FATIGUE
         subjects affected / exposed
    71 / 291 (24.40%)
    68 / 274 (24.82%)
         occurrences all number
    116
    98
    MALAISE
         subjects affected / exposed
    14 / 291 (4.81%)
    17 / 274 (6.20%)
         occurrences all number
    23
    23
    MUCOSAL INFLAMMATION
         subjects affected / exposed
    23 / 291 (7.90%)
    19 / 274 (6.93%)
         occurrences all number
    24
    28
    OEDEMA PERIPHERAL
         subjects affected / exposed
    46 / 291 (15.81%)
    33 / 274 (12.04%)
         occurrences all number
    66
    38
    Respiratory, thoracic and mediastinal disorders
    HICCUPS
         subjects affected / exposed
    16 / 291 (5.50%)
    17 / 274 (6.20%)
         occurrences all number
    35
    24
    COUGH
         subjects affected / exposed
    43 / 291 (14.78%)
    30 / 274 (10.95%)
         occurrences all number
    58
    36
    DYSPNOEA
         subjects affected / exposed
    44 / 291 (15.12%)
    40 / 274 (14.60%)
         occurrences all number
    50
    42
    EPISTAXIS
         subjects affected / exposed
    13 / 291 (4.47%)
    19 / 274 (6.93%)
         occurrences all number
    16
    22
    Psychiatric disorders
    INSOMNIA
         subjects affected / exposed
    28 / 291 (9.62%)
    18 / 274 (6.57%)
         occurrences all number
    35
    18
    Investigations
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    34 / 291 (11.68%)
    20 / 274 (7.30%)
         occurrences all number
    43
    26
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    51 / 291 (17.53%)
    27 / 274 (9.85%)
         occurrences all number
    78
    35
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    52 / 291 (17.87%)
    23 / 274 (8.39%)
         occurrences all number
    74
    29
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    45 / 291 (15.46%)
    48 / 274 (17.52%)
         occurrences all number
    116
    108
    PLATELET COUNT DECREASED
         subjects affected / exposed
    38 / 291 (13.06%)
    38 / 274 (13.87%)
         occurrences all number
    63
    69
    WEIGHT DECREASED
         subjects affected / exposed
    26 / 291 (8.93%)
    16 / 274 (5.84%)
         occurrences all number
    26
    17
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    20 / 291 (6.87%)
    29 / 274 (10.58%)
         occurrences all number
    58
    67
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    19 / 291 (6.53%)
    24 / 274 (8.76%)
         occurrences all number
    23
    27
    DYSGEUSIA
         subjects affected / exposed
    28 / 291 (9.62%)
    19 / 274 (6.93%)
         occurrences all number
    33
    19
    HEADACHE
         subjects affected / exposed
    35 / 291 (12.03%)
    24 / 274 (8.76%)
         occurrences all number
    39
    26
    PARAESTHESIA
         subjects affected / exposed
    12 / 291 (4.12%)
    14 / 274 (5.11%)
         occurrences all number
    13
    16
    Blood and lymphatic system disorders
    THROMBOCYTOPENIA
         subjects affected / exposed
    39 / 291 (13.40%)
    23 / 274 (8.39%)
         occurrences all number
    60
    37
    NEUTROPENIA
         subjects affected / exposed
    48 / 291 (16.49%)
    38 / 274 (13.87%)
         occurrences all number
    95
    65
    ANAEMIA
         subjects affected / exposed
    129 / 291 (44.33%)
    113 / 274 (41.24%)
         occurrences all number
    186
    142
    Eye disorders
    LACRIMATION INCREASED
         subjects affected / exposed
    16 / 291 (5.50%)
    18 / 274 (6.57%)
         occurrences all number
    16
    21
    Gastrointestinal disorders
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    15 / 291 (5.15%)
    5 / 274 (1.82%)
         occurrences all number
    20
    7
    CONSTIPATION
         subjects affected / exposed
    92 / 291 (31.62%)
    79 / 274 (28.83%)
         occurrences all number
    104
    96
    DIARRHOEA
         subjects affected / exposed
    60 / 291 (20.62%)
    47 / 274 (17.15%)
         occurrences all number
    88
    56
    DYSPEPSIA
         subjects affected / exposed
    16 / 291 (5.50%)
    9 / 274 (3.28%)
         occurrences all number
    18
    10
    NAUSEA
         subjects affected / exposed
    112 / 291 (38.49%)
    114 / 274 (41.61%)
         occurrences all number
    266
    206
    STOMATITIS
         subjects affected / exposed
    35 / 291 (12.03%)
    23 / 274 (8.39%)
         occurrences all number
    45
    26
    VOMITING
         subjects affected / exposed
    58 / 291 (19.93%)
    49 / 274 (17.88%)
         occurrences all number
    81
    64
    Skin and subcutaneous tissue disorders
    PRURITUS
         subjects affected / exposed
    29 / 291 (9.97%)
    16 / 274 (5.84%)
         occurrences all number
    37
    17
    DRY SKIN
         subjects affected / exposed
    20 / 291 (6.87%)
    7 / 274 (2.55%)
         occurrences all number
    23
    7
    RASH
         subjects affected / exposed
    41 / 291 (14.09%)
    21 / 274 (7.66%)
         occurrences all number
    54
    23
    Endocrine disorders
    HYPOTHYROIDISM
         subjects affected / exposed
    18 / 291 (6.19%)
    2 / 274 (0.73%)
         occurrences all number
    19
    2
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    46 / 291 (15.81%)
    26 / 274 (9.49%)
         occurrences all number
    61
    29
    BACK PAIN
         subjects affected / exposed
    40 / 291 (13.75%)
    25 / 274 (9.12%)
         occurrences all number
    51
    28
    PAIN IN EXTREMITY
         subjects affected / exposed
    23 / 291 (7.90%)
    13 / 274 (4.74%)
         occurrences all number
    23
    13
    Infections and infestations
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    16 / 291 (5.50%)
    10 / 274 (3.65%)
         occurrences all number
    22
    13
    CONJUNCTIVITIS
         subjects affected / exposed
    18 / 291 (6.19%)
    15 / 274 (5.47%)
         occurrences all number
    23
    18
    NASOPHARYNGITIS
         subjects affected / exposed
    15 / 291 (5.15%)
    8 / 274 (2.92%)
         occurrences all number
    20
    10
    PNEUMONIA
         subjects affected / exposed
    16 / 291 (5.50%)
    11 / 274 (4.01%)
         occurrences all number
    20
    12
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    78 / 291 (26.80%)
    64 / 274 (23.36%)
         occurrences all number
    101
    84
    HYPERGLYCAEMIA
         subjects affected / exposed
    15 / 291 (5.15%)
    17 / 274 (6.20%)
         occurrences all number
    17
    20
    HYPOKALAEMIA
         subjects affected / exposed
    21 / 291 (7.22%)
    4 / 274 (1.46%)
         occurrences all number
    29
    4
    HYPOMAGNESAEMIA
         subjects affected / exposed
    19 / 291 (6.53%)
    14 / 274 (5.11%)
         occurrences all number
    31
    19

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Nov 2015
    Protocol was amended to change OS rate at 3 years from Secondary Efficacy Objective to Exploratory Outcome Measure. Exclusion Criteria Treatment with systemic immunostimulatory agents within 4 weeks prior to randomization updated to include or 5 half-lives of the drug, whichever is longer.
    09 Jun 2016
    Protocol was amended to change the assessment of the patients for the objectives to chemotherapy-naive and have stage IV non-squamous NSCLC (the ITT population) treated with atezolizumab + carboplatin or cisplatin + pemetrexed (Arm A) in comparison to carboplatin or cisplatin + pemetrexed (Arm B). Previous primary efficacy objectives were removed with the exception of investigator-assessed PFS and OS was added. Secondary Efficacy Objectives were updated with the change in patient assessment. Secondary Efficacy Objective investigator-assessed PFS replaced with IRF-assessed PFS. Time to response added to Secondary Efficacy Objective. "Patients with a sensitizing mutation in the EGFR gene or an ALK fusion oncogene" added to cancer specific exclusion criteria. "Or cerebrovascular accident" added to "Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina." General Medical Exclusions. "Illness or condition that may interfere with a patient’s capacity to understand, follow, and/or comply with study procedures" added to General Medical Exclusions. "Prior treatment with EGFR inhibitors or ALK inhibitors" added to Exclusion Criteria Related to Medications. Exclusion Criteria Related to Medications updated with "Any approved anti-cancer therapy, including hormonal therapy within 21 days prior to initiation of study treatment".
    09 Oct 2017
    Protocol was amended to remove all objectives and outcome measures based on review by IRF. Secondary efficacy objective and outcome measure for SILC scale symptom severity scores has been updated so that it will be measured from baseline instead of time to deterioration (TTD).
    02 Nov 2018
    Protocol was amended to correct the end of study definition. This correction ensures that the study continues until last patient, last visit or until the Sponsor terminates the study. The contraception requirement for female patients has been clarified and text has been added to specify when women must refrain from donating eggs. The list of risks associated with atezolizumab has been revised to align with current atezolizumab risk language, and guidelines for managing patients who experience atezolizumab-associated adverse events have been revised to include nephritis.
    11 Feb 2020
    Protocol was amended to include myositis to the list of atezolizumab risks for consistency with the list of identified risks in the Atezolizumab Investigator's Brochure.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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