Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

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

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

    Results information
    Results version number
    		 v1
    This version publication date
    13 Oct 2019
    First version publication date
    13 Oct 2019
    Other versions
    		 v2 , v3

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GO29437
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02367794
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    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
    Interim
    Date of interim/final analysis
    03 Oct 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    03 Oct 2018
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this randomized, Phase III, multicenter, open-label study was to evaluate the safety and efficacy of atezolizumab in combination with carboplatin + paclitaxel or with carboplatin + nab-paclitaxel compared with treatment with carboplatin + nab-paclitaxel in approximately 1025 chemotherapy-naive patients with Stage IV squamous non-small cell lung cancer (NSCLC).
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Jun 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 12
    Country: Number of subjects enrolled
    Australia: 33
    Country: Number of subjects enrolled
    Austria: 3
    Country: Number of subjects enrolled
    Belgium: 16
    Country: Number of subjects enrolled
    Bulgaria: 9
    Country: Number of subjects enrolled
    Brazil: 27
    Country: Number of subjects enrolled
    Canada: 16
    Country: Number of subjects enrolled
    Chile: 20
    Country: Number of subjects enrolled
    Germany: 72
    Country: Number of subjects enrolled
    Spain: 142
    Country: Number of subjects enrolled
    France: 35
    Country: Number of subjects enrolled
    Israel: 21
    Country: Number of subjects enrolled
    Italy: 37
    Country: Number of subjects enrolled
    Japan: 83
    Country: Number of subjects enrolled
    Lithuania: 1
    Country: Number of subjects enrolled
    Latvia: 12
    Country: Number of subjects enrolled
    Mexico: 4
    Country: Number of subjects enrolled
    Netherlands: 16
    Country: Number of subjects enrolled
    Peru: 6
    Country: Number of subjects enrolled
    Portugal: 12
    Country: Number of subjects enrolled
    Russian Federation: 35
    Country: Number of subjects enrolled
    Singapore: 12
    Country: Number of subjects enrolled
    Slovakia: 6
    Country: Number of subjects enrolled
    Taiwan: 12
    Country: Number of subjects enrolled
    Ukraine: 178
    Country: Number of subjects enrolled
    United States: 201
    Worldwide total number of subjects
    1021
    EEA total number of subjects
    361
    Number of subjects enrolled per age group
    In utero
    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)
    476
    From 65 to 84 years
    543
    85 years and over
    2

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Subjects in this study included chemotherapy-naive patients with Stage IV 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 C: Nab-Paclitaxel + Carboplatin
    Arm description
    		 The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Subjects who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, subjects received best supportive care.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Nab-paclitaxel 100 milligrams per meter squared (mg/m^2) IV on Day 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles.

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

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab 1200 milligrams (mg) intravenous infusion (IV) on day 1 of each 21-day cycle.

    Investigational medicinal product name
    Nab-Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Nab-paclitaxel 100 milligrams per meter squared (mg/m^2) IV on Day 1, 8, and 15 of each 21-day cycle for 4 or 6 cycles

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles.

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

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel 200 mg/m^2 IV on Day 1 of each 21-day cycle for 4 or 6 cycles. Participants of Asian race/ethnicity will be administered paclitaxel 175 mg/m2 IV.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravascular use , Intravenous use
    Dosage and administration details
    Carboplatin area under the concentration curve (AUC) 6 milligrams per milliliter per minute (mg/mL/min) on Day 1 of each 21-day cycle for 4 or 6 cycles.

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab 1200 milligrams (mg) intravenous infusion (IV) on day 1 of each 21-day cycle.

    Number of subjects in period 1
    		Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Started
    340
    343
    338
    Completed
    82
    103
    89
    Not completed
    258
    240
    249
         Randomized in error
    -
    -
    1
         Consent withdrawn by subject
    25
    12
    14
         Physician decision
    -
    3
    1
         Death
    230
    223
    229
         Patient unable to receive carboplatin
    -
    -
    1
         Lost to follow-up
    1
    2
    1
         Brain metastasis
    1
    -
    -
         Protocol deviation
    1
    -
    1
         Hypercalcemia prior to C1D1
    -
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Arm C: Nab-Paclitaxel + Carboplatin
    Reporting group description
    		 The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Subjects who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, subjects received best supportive care.

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

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

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

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Arm C: Nab-Paclitaxel + Carboplatin
    Reporting group description
    		 The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Subjects who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, subjects received best supportive care.

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

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

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

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population
    End point description
    PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT population.
    End point type
    Primary
    End point timeframe
    Up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    340
    343
    338
    Units: Months
        median (confidence interval 95%)
    5.6 (5.5 to 5.7)
    6.5 (5.7 to 7.1)
    5.6 (5.5 to 6.9)
    Statistical analysis title
    		 PFS Statistical Analysis
    Comparison groups
    Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin v Arm C: Nab-Paclitaxel + Carboplatin
    Number of subjects included in analysis
    683
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0006
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 0.88

    Primary: Overall Survival (OS) in the ITT Population

    		 Close Top of page
    End point title
    		 Overall Survival (OS) in the ITT Population
    End point description
    OS is defined as the time between the date of randomization and date of death from any cause in the ITT population.
    End point type
    Primary
    End point timeframe
    Up to approximately 39 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    340
    343
    338
    Units: Months
        median (confidence interval 95%)
    13.5 (12.2 to 15.1)
    14.2 (12.3 to 16.8)
    12.6 (11.6 to 14.7)
    Statistical analysis title
    		 OS Statistical Analysis
    Comparison groups
    Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin v Arm C: Nab-Paclitaxel + Carboplatin
    Number of subjects included in analysis
    683
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1581
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 1.05

    Secondary: OS in the Tumor Gene Expression (tGE) Population

    		 Close Top of page
    End point title
    		 OS in the Tumor Gene Expression (tGE) Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 39 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [1]
    0 [2]
    0 [3]
    Units: Month
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [1] - Data will be analyzed at the time of study completion.
    [2] - Data will be analyzed at the time of study completion.
    [3] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 PFS as Determined by the Investigator Using RECIST v1.1 in the tGE Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [4]
    0 [5]
    0 [6]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [4] - Data will be analyzed at the time of study completion.
    [5] - Data will be analyzed at the time of study completion.
    [6] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [7]
    0 [8]
    0 [9]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [7] - Data will be analyzed at the time of study completion.
    [8] - Data will be analyzed at the time of study completion.
    [9] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [10]
    0 [11]
    0 [12]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [10] - Data will be analyzed at the time of study completion.
    [11] - Data will be analyzed at the time of study completion.
    [12] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 OS in the TC2/3 or IC2/3 Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 39 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [13]
    0 [14]
    0 [15]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [13] - Data will be analyzed at the time of study completion.
    [14] - Data will be analyzed at the time of study completion.
    [15] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 OS in the TC1/2/3 or IC1/2/3 Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 39 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [16]
    0 [17]
    0 [18]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [16] - Data will be analyzed at the time of study completion.
    [17] - Data will be analyzed at the time of study completion.
    [18] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [19]
    0 [20]
    0 [21]
    Units: Percentage
    Notes
    [19] - Data will be analyzed at the time of study completion.
    [20] - Data will be analyzed at the time of study completion.
    [21] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [22]
    0 [23]
    0 [24]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [22] - Data will be analyzed at the time of study completion.
    [23] - Data will be analyzed at the time of study completion.
    [24] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

    Secondary: OS at 1 and 2 Years in the ITT Population

    		 Close Top of page
    End point title
    		 OS at 1 and 2 Years in the ITT Population
    End point description
    OS rates at 1 and 2 years is defined as the proportion of participants alive at 1 and 2 years after randomization estimated using Kaplan-Meier (KM) methodology for the ITT population
    End point type
    Secondary
    End point timeframe
    1 and 2 years
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [25]
    0 [26]
    0 [27]
    Units: Months
        number (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [25] - Data will be analyzed at the time of study completion.
    [26] - Data will be analyzed at the time of study completion.
    [27] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [28]
    0 [29]
    0 [30]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [28] - Data will be analyzed at the time of study completion.
    [29] - Data will be analyzed at the time of study completion.
    [30] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months after the first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [31]
    0 [32]
    0 [33]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [31] - Data will be analyzed at the time of study completion.
    [32] - Data will be analyzed at the time of study completion.
    [33] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Change from Baseline in Patient-reported Lung Cancer Symptoms Score using the SILC Scale Symptom Severity Score in the ITT Population
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [34]
    0 [35]
    0 [36]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [34] - Data will be analyzed at the time of study completion.
    [35] - Data will be analyzed at the time of study completion.
    [36] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A vs. Arm B)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 30 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [37]
    0 [38]
    0 [39]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [37] - Data will be analyzed at the time of study completion.
    [38] - Data will be analyzed at the time of study completion.
    [39] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 OS in the ITT Population (Arm A vs. Arm B)
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 39 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [40]
    0 [41]
    0 [42]
    Units: Months
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [40] - Data will be analyzed at the time of study completion.
    [41] - Data will be analyzed at the time of study completion.
    [42] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Adverse Events

    		 Close Top of page
    End point title
    		 Percentage of Participants With Adverse Events
    End point description
    End point type
    Secondary
    End point timeframe
    Up to approximately 39 months after first participant enrolled
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [43]
    0 [44]
    0 [45]
    Units: Percentage
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [43] - Data will be analyzed at the time of study completion.
    [44] - Data will be analyzed at the time of study completion.
    [45] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

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

    		 Close Top of page
    End point title
    		 Percentage of Participants with Anti-therapeutic Antibody (ATA) Response to Atezolizumab
    End point description
    The predose samples will be collected on the same day of treatment administration.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle thereafter (up to 39 months), at treatment discontinuation (up to 39 months), and at 120 days after the last dose of atezolizumab (up to approximately 39 months, each cycle is 21 days)
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [46]
    0 [47]
    0 [48]
    Units: Percentage
        geometric mean (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [46] - Data will be analyzed at the time of study completion.
    [47] - Data will be analyzed at the time of study completion.
    [48] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

    Secondary: Maximum Observed Serum Atezolizumab Concentration (Cmax)

    		 Close Top of page
    End point title
    		 Maximum Observed Serum Atezolizumab Concentration (Cmax)
    End point description
    The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle up to 39 months; 30 minutes postdose on Day 1 of Cycles 1 and 3; at treatment discontinuation (up to 39 months), and at 120 days after last dose of atezolizumab (up to 39 months, each cycle is 21 days)
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [49]
    0 [50]
    0 [51]
    Units: mcg/mL
        geometric mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [49] - Data will be analyzed at the time of study completion.
    [50] - Data will be analyzed at the time of study completion.
    [51] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

    Secondary: Minimum Observed Serum Atezolizumab Concentration (Cmin)

    		 Close Top of page
    End point title
    		 Minimum Observed Serum Atezolizumab Concentration (Cmin)
    End point description
    The predose samples will be collected on the same day of treatment administration.
    End point type
    Secondary
    End point timeframe
    Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle thereafter (up to 39 months), at treatment discontinuation (up to 39 months), and at 120 days after the last dose of atezolizumab (up to approximately 39 months, each cycle is 21 days)
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [52]
    0 [53]
    0 [54]
    Units: mcg/mL
        geometric mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [52] - Data will be analyzed at the time of study completion.
    [53] - Data will be analyzed at the time of study completion.
    [54] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

    Secondary: Plasma Concentrations for Paclitaxel

    		 Close Top of page
    End point title
    		 Plasma Concentrations for Paclitaxel
    End point description
    End point type
    Secondary
    End point timeframe
    Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 180 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [55]
    0 [56]
    0 [57]
    Units: mcg/mL
        geometric mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [55] - Data will be analyzed at the time of study completion.
    [56] - Data will be analyzed at the time of study completion.
    [57] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

    Secondary: Plasma Concentrations for Nab-Paclitaxel

    		 Close Top of page
    End point title
    		 Plasma Concentrations for Nab-Paclitaxel
    End point description
    End point type
    Secondary
    End point timeframe
    Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [58]
    0 [59]
    0 [60]
    Units: mcg/mL
        geometric mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [58] - Data will be analyzed at the time of study completion.
    [59] - Data will be analyzed at the time of study completion.
    [60] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

    Secondary: Plasma Concentrations for Carboplatin

    		 Close Top of page
    End point title
    		 Plasma Concentrations for Carboplatin
    End point description
    End point type
    Secondary
    End point timeframe
    Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 15 to 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)
    End point values
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Number of subjects analysed
    0 [61]
    0 [62]
    0 [63]
    Units: mcg/mL
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    Notes
    [61] - Data will be analyzed at the time of study completion.
    [62] - Data will be analyzed at the time of study completion.
    [63] - Data will be analyzed at the time of study completion.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the first study drug administration to the data cutoff date: 3 October 2018.
    Adverse event reporting additional description
    Safety-evaluable population included all participants who received at least one dose of any study medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MeDRA Version 21.1
    Dictionary version
    21.1
    Reporting groups
    Reporting group title
    Arm C: Nab-Paclitaxel + Carboplatin
    Reporting group description
    		 The induction phase of the study consisted of four or six cycles; carboplatin was administered on Day 1 of each 21-day cycle, nab-paclitaxel was administered on Days 1, 8, and 15 of each 21-day cycle. The Day 1 order of drug administration was as follows: nab-paclitaxel, then carboplatin. Participants who experienced disease progression at any time during the induction phase discontinued all study treatment. In the maintenance phase, participants received best supportive care.

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

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

    Serious adverse events
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    96 / 334 (28.74%)
    160 / 334 (47.90%)
    143 / 332 (43.07%)
         number of deaths (all causes)
    242
    221
    233
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign Salivary Gland Neoplasm
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colon Cancer
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gallbladder Adenocarcinoma
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected Neoplasm
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Prostate Cancer
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tumour Embolism
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Vascular disorders
    Deep Vein Thrombosis
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Haemodynamic Instability
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic Hypotension
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral Arterial Occlusive Disease
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Superior Vena Cava Syndrome
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Surgical and medical procedures
    Therapeutic Embolisation
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest Pain
         subjects affected / exposed
    2 / 334 (0.60%)
    0 / 334 (0.00%)
    3 / 332 (0.90%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 334 (0.00%)
    7 / 334 (2.10%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 7
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 7
    1 / 2
    Fatigue
         subjects affected / exposed
    0 / 334 (0.00%)
    3 / 334 (0.90%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gait Disturbance
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 334 (0.30%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mucosal Inflammation
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-Cardiac Chest Pain
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Performance Status Decreased
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    5 / 334 (1.50%)
    5 / 334 (1.50%)
    5 / 332 (1.51%)
         occurrences causally related to treatment / all
    3 / 6
    0 / 5
    3 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic Reaction
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug Hypersensitivity
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemophagocytic Lymphohistiocytosis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatitis
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    Atelectasis
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchial Haemorrhage
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic Obstructive Pulmonary Disease
         subjects affected / exposed
    3 / 334 (0.90%)
    6 / 334 (1.80%)
    10 / 332 (3.01%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 6
    1 / 14
         deaths causally related to treatment / all
    0 / 1
    0 / 3
    0 / 1
    Cough
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diaphragmatic Paralysis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    3 / 334 (0.90%)
    6 / 334 (1.80%)
    6 / 332 (1.81%)
         occurrences causally related to treatment / all
    0 / 4
    1 / 7
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Dyspnoea at Rest
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea Exertional
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 334 (0.60%)
    5 / 334 (1.50%)
    5 / 332 (1.51%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    1 / 3
    Hypoxia
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Interstitial Lung Disease
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngeal Haemorrhage
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung Consolidation
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung Disorder
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paranasal Cyst
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural Effusion
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Aspiration
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 334 (0.60%)
    10 / 334 (2.99%)
    11 / 332 (3.31%)
         occurrences causally related to treatment / all
    2 / 2
    10 / 10
    11 / 11
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Pneumothorax
         subjects affected / exposed
    3 / 334 (0.90%)
    3 / 334 (0.90%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax Spontaneous
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Embolism
         subjects affected / exposed
    3 / 334 (0.90%)
    3 / 334 (0.90%)
    7 / 332 (2.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 7
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    Pulmonary Oedema
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory Failure
         subjects affected / exposed
    3 / 334 (0.90%)
    2 / 334 (0.60%)
    3 / 332 (0.90%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    2 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Psychiatric disorders
    Completed Suicide
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Confusional State
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hallucination
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mental Status Changes
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicidal Ideation
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device Dislocation
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood Bilirubin Increased
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood Creatinine Increased
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood Lactic Acid Increased
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General Physical Condition Abnormal
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Liver Function Test Abnormal
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutrophil Count Decreased
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    3 / 332 (0.90%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Platelet Count Decreased
         subjects affected / exposed
    2 / 334 (0.60%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Weight Decreased
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Alcohol Poisoning
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest Injury
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fermur Fracture
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip Fracture
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Humerus Fracture
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infusion Related Reaction
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Periorbital Haematoma
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radiation Oesophagitis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radiation Pneumonitis
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib Fracture
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin Laceration
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural Haematoma
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic Vertebral Fracture
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Toxicity to Various Agents
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Tracheo-Oesophageal Fistula
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute Myocardial Infarction
         subjects affected / exposed
    1 / 334 (0.30%)
    2 / 334 (0.60%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    3 / 334 (0.90%)
    2 / 334 (0.60%)
    6 / 332 (1.81%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial Flutter
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    5 / 332 (1.51%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    3 / 5
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Atrial Thrombosis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac Arrest
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    Cardiac Failure
         subjects affected / exposed
    1 / 334 (0.30%)
    2 / 334 (0.60%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac Failure Acute
         subjects affected / exposed
    2 / 334 (0.60%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    1 / 1
    Cardiac Tamponade
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-Respiratory Arrest
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Coronary Artery Stenosis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Left Ventricular Dysfunction
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial Infarction
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pericardial Effusion
         subjects affected / exposed
    0 / 334 (0.00%)
    4 / 334 (1.20%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinus Tachycardia
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain Oedema
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral Ischaemia
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular Accident
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    4 / 332 (1.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Depressed Level of Consciousness
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Embolic Stroke
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre Syndrome
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Hemiplegia
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperaesthesia
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypotonia
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic Stroke
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Motor Dysfunction
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myxoedema Coma
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal Cord Compression
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 334 (0.90%)
    7 / 334 (2.10%)
    6 / 332 (1.81%)
         occurrences causally related to treatment / all
    2 / 3
    6 / 7
    5 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ferbrile Neutropenia
         subjects affected / exposed
    5 / 334 (1.50%)
    13 / 334 (3.89%)
    16 / 332 (4.82%)
         occurrences causally related to treatment / all
    5 / 5
    15 / 15
    15 / 16
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemolysis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    3 / 334 (0.90%)
    3 / 334 (0.90%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    2 / 3
    3 / 3
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    2 / 334 (0.60%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 334 (0.30%)
    2 / 334 (0.60%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal Detachment
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal Haemorrhage
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 334 (0.00%)
    3 / 334 (0.90%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    4 / 334 (1.20%)
    6 / 334 (1.80%)
    3 / 332 (0.90%)
         occurrences causally related to treatment / all
    4 / 5
    4 / 6
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal Perforation
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Gastritis
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Haemorrhage
         subjects affected / exposed
    2 / 334 (0.60%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Gastrointestinal Necrosis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Perforation
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal Toxicity
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal Hernia
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal Perforation
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large Intestine Perforation
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Nausea
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis Chronic
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal Haemorrhage
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small Intestinal Obstruction
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Gastrointestinal Haemorrhage
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Autoimmune Hepatitis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bile Duct Stone
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis Acute
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Drug-Induced Liver Injury
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic Function Abnormal
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis Toxic
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune-Mediated Hepatitis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis Acneiform
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erythema Multiforme
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute Kidney Injury
         subjects affected / exposed
    1 / 334 (0.30%)
    4 / 334 (1.20%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Retention
         subjects affected / exposed
    1 / 334 (0.30%)
    2 / 334 (0.60%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Adrenal Insufficiency
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperthyroidism
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypopituitarism
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    5 / 332 (1.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Flank Pain
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal Chest Pain
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal Pain
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pathological Fracture
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polyarthritis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polymyositis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal Infection
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 334 (0.30%)
    3 / 334 (0.90%)
    5 / 332 (1.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clostridium Difficle Infection
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colonic Abscess
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device Related Infection
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocarditis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis Infection
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infected Dermal Cyst
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infection Exacerbation of Chronic Obstructive Ariways Disease
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Lower Respiratory Tract Infection
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung Abscess
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung Infection
         subjects affected / exposed
    7 / 334 (2.10%)
    1 / 334 (0.30%)
    5 / 332 (1.51%)
         occurrences causally related to treatment / all
    3 / 7
    0 / 1
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Meningitis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural Infection
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    14 / 334 (4.19%)
    30 / 334 (8.98%)
    25 / 332 (7.53%)
         occurrences causally related to treatment / all
    6 / 14
    6 / 34
    5 / 27
         deaths causally related to treatment / all
    1 / 1
    2 / 6
    1 / 3
    Pneumonia Bacterial
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Haemophilus
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Staphylococcal
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Streptococcal
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal Sepsis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary Sepsis
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    3 / 334 (0.90%)
    2 / 334 (0.60%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    6 / 334 (1.80%)
    5 / 334 (1.50%)
    9 / 332 (2.71%)
         occurrences causally related to treatment / all
    2 / 6
    1 / 5
    2 / 10
         deaths causally related to treatment / all
    0 / 2
    0 / 2
    1 / 3
    Septic Shock
         subjects affected / exposed
    1 / 334 (0.30%)
    3 / 334 (0.90%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
    Sinusitis
         subjects affected / exposed
    1 / 334 (0.30%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatococcal Infection
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    3 / 334 (0.90%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection Staphylococcal
         subjects affected / exposed
    1 / 334 (0.30%)
    0 / 334 (0.00%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 334 (0.60%)
    3 / 334 (0.90%)
    4 / 332 (1.20%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 3
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes Mellitus
         subjects affected / exposed
    0 / 334 (0.00%)
    0 / 334 (0.00%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Failure to Thrive
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    2 / 334 (0.60%)
    1 / 334 (0.30%)
    2 / 332 (0.60%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 334 (0.00%)
    2 / 334 (0.60%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    3 / 334 (0.90%)
    2 / 334 (0.60%)
    1 / 332 (0.30%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 2 Diabetes Mellitus
         subjects affected / exposed
    0 / 334 (0.00%)
    1 / 334 (0.30%)
    0 / 332 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Arm C: Nab-Paclitaxel + Carboplatin Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin Arm A: Atezolizumab + Paclitaxel + Carboplatin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    315 / 334 (94.31%)
    325 / 334 (97.31%)
    315 / 332 (94.88%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    11 / 334 (3.29%)
    18 / 334 (5.39%)
    22 / 332 (6.63%)
         occurrences all number
    17
    25
    25
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    66 / 334 (19.76%)
    58 / 334 (17.37%)
    77 / 332 (23.19%)
         occurrences all number
    85
    79
    99
    Chest Pain
         subjects affected / exposed
    18 / 334 (5.39%)
    24 / 334 (7.19%)
    27 / 332 (8.13%)
         occurrences all number
    19
    29
    29
    Fatigue
         subjects affected / exposed
    88 / 334 (26.35%)
    103 / 334 (30.84%)
    95 / 332 (28.61%)
         occurrences all number
    101
    127
    109
    Malaise
         subjects affected / exposed
    16 / 334 (4.79%)
    17 / 334 (5.09%)
    10 / 332 (3.01%)
         occurrences all number
    24
    25
    14
    Mucosal Inflammation
         subjects affected / exposed
    9 / 334 (2.69%)
    16 / 334 (4.79%)
    17 / 332 (5.12%)
         occurrences all number
    11
    23
    17
    Oedema Peripheral
         subjects affected / exposed
    22 / 334 (6.59%)
    26 / 334 (7.78%)
    22 / 332 (6.63%)
         occurrences all number
    25
    31
    27
    Pyrexia
         subjects affected / exposed
    34 / 334 (10.18%)
    44 / 334 (13.17%)
    44 / 332 (13.25%)
         occurrences all number
    42
    65
    63
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    51 / 334 (15.27%)
    59 / 334 (17.66%)
    59 / 332 (17.77%)
         occurrences all number
    61
    74
    67
    Dysphonia
         subjects affected / exposed
    11 / 334 (3.29%)
    18 / 334 (5.39%)
    14 / 332 (4.22%)
         occurrences all number
    11
    18
    14
    Dyspnoea
         subjects affected / exposed
    57 / 334 (17.07%)
    66 / 334 (19.76%)
    61 / 332 (18.37%)
         occurrences all number
    65
    94
    72
    Epistaxis
         subjects affected / exposed
    37 / 334 (11.08%)
    34 / 334 (10.18%)
    8 / 332 (2.41%)
         occurrences all number
    43
    37
    9
    Haemoptysis
         subjects affected / exposed
    18 / 334 (5.39%)
    18 / 334 (5.39%)
    18 / 332 (5.42%)
         occurrences all number
    27
    28
    20
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    27 / 334 (8.08%)
    30 / 334 (8.98%)
    29 / 332 (8.73%)
         occurrences all number
    28
    34
    31
    Investigations
    Alanine Aminotransferase Increased
         subjects affected / exposed
    18 / 334 (5.39%)
    40 / 334 (11.98%)
    33 / 332 (9.94%)
         occurrences all number
    23
    61
    53
    Aspartate Aminotransferase Increased
         subjects affected / exposed
    17 / 334 (5.09%)
    34 / 334 (10.18%)
    30 / 332 (9.04%)
         occurrences all number
    27
    60
    50
    Blood Alkaline Phosphatase Increased
         subjects affected / exposed
    8 / 334 (2.40%)
    13 / 334 (3.89%)
    25 / 332 (7.53%)
         occurrences all number
    8
    14
    33
    Blood Creatinine Increased
         subjects affected / exposed
    3 / 334 (0.90%)
    23 / 334 (6.89%)
    13 / 332 (3.92%)
         occurrences all number
    4
    26
    13
    Neutrophil Count Decreased
         subjects affected / exposed
    65 / 334 (19.46%)
    60 / 334 (17.96%)
    17 / 332 (5.12%)
         occurrences all number
    145
    132
    24
    Platelet Count Decreased
         subjects affected / exposed
    59 / 334 (17.66%)
    59 / 334 (17.66%)
    40 / 332 (12.05%)
         occurrences all number
    110
    125
    64
    Weight Decreased
         subjects affected / exposed
    14 / 334 (4.19%)
    29 / 334 (8.68%)
    20 / 332 (6.02%)
         occurrences all number
    14
    34
    21
    White Blood Cell Count Decreased
         subjects affected / exposed
    36 / 334 (10.78%)
    32 / 334 (9.58%)
    12 / 332 (3.61%)
         occurrences all number
    68
    64
    19
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    32 / 334 (9.58%)
    31 / 334 (9.28%)
    31 / 332 (9.34%)
         occurrences all number
    41
    36
    33
    Dysgeusia
         subjects affected / exposed
    30 / 334 (8.98%)
    31 / 334 (9.28%)
    16 / 332 (4.82%)
         occurrences all number
    31
    35
    16
    Headache
         subjects affected / exposed
    18 / 334 (5.39%)
    30 / 334 (8.98%)
    37 / 332 (11.14%)
         occurrences all number
    26
    35
    43
    Neuropathy Peripherial
         subjects affected / exposed
    35 / 334 (10.48%)
    34 / 334 (10.18%)
    66 / 332 (19.88%)
         occurrences all number
    38
    39
    73
    Paraesthesia
         subjects affected / exposed
    15 / 334 (4.49%)
    16 / 334 (4.79%)
    26 / 332 (7.83%)
         occurrences all number
    16
    17
    31
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    30 / 334 (8.98%)
    48 / 334 (14.37%)
    55 / 332 (16.57%)
         occurrences all number
    35
    54
    68
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    193 / 334 (57.78%)
    186 / 334 (55.69%)
    128 / 332 (38.55%)
         occurrences all number
    244
    250
    154
    Leukopenia
         subjects affected / exposed
    34 / 334 (10.18%)
    42 / 334 (12.57%)
    8 / 332 (2.41%)
         occurrences all number
    54
    86
    8
    Neutropenia
         subjects affected / exposed
    122 / 334 (36.53%)
    121 / 334 (36.23%)
    42 / 332 (12.65%)
         occurrences all number
    212
    260
    59
    Thrombocytopenia
         subjects affected / exposed
    92 / 334 (27.54%)
    90 / 334 (26.95%)
    46 / 332 (13.86%)
         occurrences all number
    170
    161
    66
    Gastrointestinal disorders
    Abdominal Pain Upper
         subjects affected / exposed
    17 / 334 (5.09%)
    12 / 334 (3.59%)
    12 / 332 (3.61%)
         occurrences all number
    17
    15
    15
    Constipation
         subjects affected / exposed
    72 / 334 (21.56%)
    101 / 334 (30.24%)
    75 / 332 (22.59%)
         occurrences all number
    84
    124
    93
    Diarrhoea
         subjects affected / exposed
    77 / 334 (23.05%)
    88 / 334 (26.35%)
    93 / 332 (28.01%)
         occurrences all number
    107
    128
    114
    Nausea
         subjects affected / exposed
    96 / 334 (28.74%)
    129 / 334 (38.62%)
    93 / 332 (28.01%)
         occurrences all number
    136
    197
    133
    Stomatitis
         subjects affected / exposed
    15 / 334 (4.49%)
    22 / 334 (6.59%)
    19 / 332 (5.72%)
         occurrences all number
    17
    26
    22
    Vomitting
         subjects affected / exposed
    48 / 334 (14.37%)
    63 / 334 (18.86%)
    49 / 332 (14.76%)
         occurrences all number
    59
    78
    62
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    102 / 334 (30.54%)
    113 / 334 (33.83%)
    130 / 332 (39.16%)
         occurrences all number
    103
    113
    134
    Dry Skin
         subjects affected / exposed
    5 / 334 (1.50%)
    17 / 334 (5.09%)
    13 / 332 (3.92%)
         occurrences all number
    5
    18
    14
    Pruritus
         subjects affected / exposed
    12 / 334 (3.59%)
    20 / 334 (5.99%)
    32 / 332 (9.64%)
         occurrences all number
    13
    29
    42
    Rash
         subjects affected / exposed
    18 / 334 (5.39%)
    42 / 334 (12.57%)
    41 / 332 (12.35%)
         occurrences all number
    19
    47
    53
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    2 / 334 (0.60%)
    31 / 334 (9.28%)
    25 / 332 (7.53%)
         occurrences all number
    2
    36
    26
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    22 / 334 (6.59%)
    38 / 334 (11.38%)
    61 / 332 (18.37%)
         occurrences all number
    25
    51
    80
    Back Pain
         subjects affected / exposed
    16 / 334 (4.79%)
    36 / 334 (10.78%)
    31 / 332 (9.34%)
         occurrences all number
    17
    40
    35
    Bone Pain
         subjects affected / exposed
    3 / 334 (0.90%)
    9 / 334 (2.69%)
    22 / 332 (6.63%)
         occurrences all number
    3
    11
    34
    Musculoskeletal Pain
         subjects affected / exposed
    13 / 334 (3.89%)
    21 / 334 (6.29%)
    26 / 332 (7.83%)
         occurrences all number
    16
    28
    32
    Myalgia
         subjects affected / exposed
    19 / 334 (5.69%)
    22 / 334 (6.59%)
    43 / 332 (12.95%)
         occurrences all number
    24
    23
    62
    Pain in Extremity
         subjects affected / exposed
    17 / 334 (5.09%)
    31 / 334 (9.28%)
    35 / 332 (10.54%)
         occurrences all number
    17
    34
    46
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    8 / 334 (2.40%)
    17 / 334 (5.09%)
    17 / 332 (5.12%)
         occurrences all number
    10
    18
    27
    Pneumonia
         subjects affected / exposed
    13 / 334 (3.89%)
    17 / 334 (5.09%)
    14 / 332 (4.22%)
         occurrences all number
    14
    18
    14
    Respiratory Tract Infection
         subjects affected / exposed
    6 / 334 (1.80%)
    9 / 334 (2.69%)
    22 / 332 (6.63%)
         occurrences all number
    6
    13
    34
    Upper Respiratory Tract Infection
         subjects affected / exposed
    6 / 334 (1.80%)
    17 / 334 (5.09%)
    15 / 332 (4.52%)
         occurrences all number
    6
    23
    23
    Urinary Tract Infection
         subjects affected / exposed
    14 / 334 (4.19%)
    25 / 334 (7.49%)
    16 / 332 (4.82%)
         occurrences all number
    18
    39
    21
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    84 / 334 (25.15%)
    83 / 334 (24.85%)
    92 / 332 (27.71%)
         occurrences all number
    98
    107
    106
    Dehydration
         subjects affected / exposed
    11 / 334 (3.29%)
    23 / 334 (6.89%)
    20 / 332 (6.02%)
         occurrences all number
    15
    33
    30
    Hyperglycaemia
         subjects affected / exposed
    17 / 334 (5.09%)
    18 / 334 (5.39%)
    25 / 332 (7.53%)
         occurrences all number
    19
    24
    28
    Hypokalaemia
         subjects affected / exposed
    23 / 334 (6.89%)
    28 / 334 (8.38%)
    24 / 332 (7.23%)
         occurrences all number
    28
    35
    30
    Hypomagnesaemia
         subjects affected / exposed
    38 / 334 (11.38%)
    53 / 334 (15.87%)
    35 / 332 (10.54%)
         occurrences all number
    56
    78
    40

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Mar 2015
    Protocol was amended to clarify the inclusion criterion on contraception. In addition, reporting for serious adverse events and adverse events of special interest has been extended to 90 days after last dose of study treatment or until intitation of a new anticancer therapy, whichever occurs first.
    14 Aug 2015
    Protocol was amended to update the contraception requirements in the inclusion and exclusion criteria and the pregnancy-reporting information to be consistent with safety information for nab-paclitaxel. The study inclusion criteria have been modified, on the basis of an expanding safety database, to allow for patients with treated, asymptomatic cerebellar metastases to be enrolled provided specific criteria are met. The exclusion criteria for history of autoimmune disease has been broadened, on the basis of an expanding safety database, to allow for patients with eczema, psoriasis, or lichen simplex chronicus of vitiligo with dermatologic manifestations only to be permitted provided that they meet the specific conditions. The study exclusion criteria regarding treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the drug (whichever is shorter) prior to randomization has been modified to 4 weeks prior to randomization for consistency with more recent atezolizumab protocols. The exclusion criterion specifying that patients with a history of allergic reaction to intravenous contrast that requires steroid pretreatment should have baseline and subsequent tumor assessments performed via magnetic resonance imaging (MRI) has been removed.
    11 Nov 2015
    Protocol was amended to clarify that a wash-out period of at least 4 weeks or five half-lives, whichever is longer, of any systemic immunomodulatory agent is required prior to enrollment.
    15 Jun 2016
    Protocol was amended to add a co-primary endpoint of overall survival (OS) to the progression-free survival (PFS) primary endpoint. A secondary efficacy objective and outcome measure was added to evaluate the efficacy of atezolizumab + carboplatin + nab-paclitaxel compared with carboplatin + nab-paclitaxel as measured by investigator-assessed time to response (TTR) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) for both the ITT and PD-L1−selected populations. The inclusion criteria was modified to specify that patients who have received prior radiotherapy with curative intent must be treatment-free for at least a 6-month interval prior to randomization. Based on the half-life of atezolizumab of 27 days, the language regarding length of female patient contraception and follow-up of pregnancy reporting has been revised from 90 days to 5 months. The contraception requirements for male patients and pregnancy-reporting requirements for female partners of male patients who receive atezolizumab have been updated on the basis of the safety information for atezolizumab.
    01 Mar 2017
    Protocol was amended to include changes in the primary analysis populations fr the co-primary endpoints of progression-free survival (PFS) and overall survival (OS). OS will be analyzed in the intent-to-treat (ITT) population, PFS will be analyzed in the ITT population with a defined level of expression of a PD-L1 and T-effector gene signature in tumor tissue as determined by an RNA-based assay.
    24 Oct 2018
    Protocol was amended to include correction to the end of study definition. This correction ensures that the study continues until last patient, last visit or until the Sponsor terminates the stud. Inclusion criterion has been modified to address female contraception to specify when women must refrain from donating eggs.

    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.

    European Medicines Agency © 1995-Thu May 02 22:54:49 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA