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    Clinical Trial Results:
    A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy

    Summary
    EudraCT number
    		 2015-004105-16
    Trial protocol
    		 DE   DK   CZ   GB   PT   PL   ES   IE   BE   SK   BG   IT   RO  
    Global end of trial date

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 May 2023
    First version publication date
    05 May 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MO29872
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03191786
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    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
    30 Apr 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    30 Apr 2022
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    This study evaluated the efficacy and safety of atezolizumab compared with single agent chemotherapy with respect to antitumor effects in participants with treatment-naïve locally advanced or metastatic non-small cell lung cancer (NSCLC) who are deemed unsuitable for any platinum-doublet chemotherapy.
    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 Sep 2017
    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: 7
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    Bulgaria: 6
    Country: Number of subjects enrolled
    Brazil: 20
    Country: Number of subjects enrolled
    Canada: 19
    Country: Number of subjects enrolled
    Switzerland: 11
    Country: Number of subjects enrolled
    China: 55
    Country: Number of subjects enrolled
    Colombia: 18
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    Germany: 42
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    Spain: 48
    Country: Number of subjects enrolled
    United Kingdom: 47
    Country: Number of subjects enrolled
    India: 38
    Country: Number of subjects enrolled
    Ireland: 4
    Country: Number of subjects enrolled
    Italy: 30
    Country: Number of subjects enrolled
    Kazakhstan: 8
    Country: Number of subjects enrolled
    Mexico: 16
    Country: Number of subjects enrolled
    Poland: 40
    Country: Number of subjects enrolled
    Portugal: 4
    Country: Number of subjects enrolled
    Romania: 6
    Country: Number of subjects enrolled
    Slovakia: 3
    Country: Number of subjects enrolled
    Viet Nam: 15
    Worldwide total number of subjects
    453
    EEA total number of subjects
    199
    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)
    65
    From 65 to 84 years
    364
    85 years and over
    24

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study included participants with treatment-naïve locally advanced or metastatic non-small cell lung cancer (NSCLC) who were deemed unsuitable for any platinum-doublet chemotherapy.

    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
    		 Atezolizumab
    Arm description
    		 Participants received atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Atezolizumab
    Investigational medicinal product code
    Other name
    Tecentriq, MPDL3280A
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Atezolizumab was administered at a dose of 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.

    Arm title
    		 Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Arm description
    		 Participants received single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator’s choice.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Gemzar
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Gemcitabine was administered per relevant local guidelines and SmPC management.

    Investigational medicinal product name
    Vinorelbine
    Investigational medicinal product code
    Other name
    Navelbine
    Pharmaceutical forms
    Capsule, Infusion
    Routes of administration
    Oral use, Intravenous use
    Dosage and administration details
    Vinorelbine was administered per relevant local guidelines and Summary of Product Characteristics (SmPC) management.

    Number of subjects in period 1
    		Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Started
    302
    151
    Completed
    15
    0
    Not completed
    287
    151
         Adverse event, serious fatal
    236
    127
         Physician decision
    1
    -
         Consent withdrawn by subject
    26
    16
         Study Terminated By Sponsor
    15
    5
         Lost to follow-up
    9
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Atezolizumab
    Reporting group description
    		 Participants received atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.

    Reporting group title
    Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Reporting group description
    		 Participants received single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator’s choice.

    Reporting group values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine) Total
    Number of subjects
    		 302 151 453
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 46 19 65
        From 65-84 years
    		 241 123 364
        85 years and over
    		 15 9 24
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 73.6 ± 9.1 73.8 ± 8.5 -
    Sex: Female, Male
    Units: Participants
        Female
    		 82 43 125
        Male
    		 220 108 328
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 12 9 21
        Asian
    		 75 38 113
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 2 1 3
        White
    		 203 95 298
        More than one race
    		 6 6 12
        Unknown or Not Reported
    		 4 2 6
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 47 23 70
        Not Hispanic or Latino
    		 242 125 367
        Unknown or Not Reported
    		 13 3 16

    End points

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    End points reporting groups
    Reporting group title
    Atezolizumab
    Reporting group description
    		 Participants received atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.

    Reporting group title
    Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Reporting group description
    		 Participants received single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator’s choice.

    Primary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Overall survival is defined as the time between the date of randomization and the date of death due to any cause.
    End point type
    Primary
    End point timeframe
    From randomization up to death from any cause (up to approximately 55 months)
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    302
    151
    Units: Months
        median (confidence interval 95%)
    10.3 (9.4 to 11.9)
    9.2 (5.9 to 11.2)
    Statistical analysis title
    		 OS Statistical Analysis
    Statistical analysis description
    Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.028
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.63
         upper limit
    		 0.97

    Secondary: OS Rates at the 6, 12, 18, 24-Months Timepoints

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    End point title
    		 OS Rates at the 6, 12, 18, 24-Months Timepoints
    End point description
    OS rate at 6, 12, 18 and 24 months were estimated for each treatment arm.
    End point type
    Secondary
    End point timeframe
    6, 12, 18 and 24 months
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    302
    151
    Units: Percentage
    number (confidence interval 95%)
        6 Months
    64.0 (58.6 to 69.5)
    57.5 (49.4 to 65.7)
        12 Months
    43.7 (37.9 to 49.4)
    38.6 (30.5 to 46.7)
        18 Months
    31.4 (26.0 to 36.8)
    24.0 (16.8 to 31.2)
        24 Months
    24.3 (19.3 to 29.4)
    12.4 (6.7 to 18.0)
    Statistical analysis title
    		 OS Rate at 6 Months Statistical Analysis
    Statistical analysis description
    OS Rate at 6 Months
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in OS Rates
    Point estimate
    6.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 16.3
    Statistical analysis title
    		 OS Rate at 24 Months Statistical Analysis
    Statistical analysis description
    OS Rate at 24 Months
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in OS Rates
    Point estimate
    11.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.4
         upper limit
    		 19.5
    Statistical analysis title
    		 OS Rate at 18 Months Statistical Analysis
    Statistical analysis description
    OS Rate at 18 Months
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in OS Rates
    Point estimate
    7.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 16.5
    Statistical analysis title
    		 OS Rate at 12 Months Statistical Analysis
    Statistical analysis description
    OS Rate at 12 Months
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Difference in OS Rates
    Point estimate
    5.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.9
         upper limit
    		 15

    Secondary: Percentage of Participants With Objective Response Rate, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1)

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    End point title
    		 Percentage of Participants With Objective Response Rate, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1)
    End point description
    Objective response rate (ORR) is defined as a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as determined by the investigator with use of RECIST v1.1. A minimum interval of 6 weeks (42 days) will be considered for Stable Disease (SD) to be assigned as best overall response, i.e. in the case the single response is SD, PR or CR, this single response must have been assessed no less than 6 weeks (at least 42 days) after start date of study treatment.
    End point type
    Secondary
    End point timeframe
    From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    302
    151
    Units: Percentage of participants
        number (confidence interval 95%)
    16.9 (12.8 to 21.6)
    7.9 (4.2 to 13.5)
    No statistical analyses for this end point

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

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    End point title
    		 Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1
    End point description
    DOR is defined as the time from the first tumor assessment that supports the participants' objective response (CR or PR, whichever is first reported) to documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first, among patients who have a best overall response as CR or PR.
    End point type
    Secondary
    End point timeframe
    Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    51
    12
    Units: Months
        median (confidence interval 95%)
    14.0 (8.1 to 20.3)
    7.8 (4.8 to 9.7)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1

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    End point title
    		 Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1
    End point description
    PFS is defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1 or death from any cause, whichever occurs first.
    End point type
    Secondary
    End point timeframe
    From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    302
    151
    Units: Months
        median (confidence interval 95%)
    4.2 (3.7 to 5.5)
    4.0 (2.9 to 5.4)
    Statistical analysis title
    		 PFS Statistical Analysis
    Statistical analysis description
    Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.182
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.07

    Secondary: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC-QLQ-C30) Score

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    End point title
    		 Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC-QLQ-C30) Score
    End point description
    EORTC QLQ-C30 is a self-report measure that consists of 30 questions that assess five aspects of patient functioning, three symptom scales, global health/quality of life, and six single items. EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by participants as clinically significant (Osoba et al. 1998). '99999'=standard deviation (SD) non-estimable due to 1 participant evaluated. '00000'=data not reported due to no participant evaluated. 'SFUV'=Safety Follow-Up Visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    302
    151
    Units: units of a scale
    arithmetic mean (standard deviation)
        GHS/HRQoL Scale Score, Baseline (n=291, 146)
    54.70 ± 22.00
    55.25 ± 21.06
        GHS/HRQoL Scale Score, Week 6 (n=219, 115)
    2.09 ± 24.11
    0.29 ± 22.94
        GHS/HRQoL Scale Score, Week 12 (n=148, 63)
    2.76 ± 23.42
    1.85 ± 19.94
        GHS/HRQoL Scale Score, Week 18 (n=121, 40)
    4.20 ± 24.27
    -0.42 ± 19.52
        GHS/HRQoL Scale Score, Week 24 (n=105, 29)
    4.92 ± 23.90
    -1.72 ± 18.82
        GHS/HRQoL Scale Score, Week 30 (n=83, 22)
    4.32 ± 21.12
    2.65 ± 13.70
        GHS/HRQoL Scale Score, Week 36 (n=62, 16)
    8.20 ± 23.55
    -0.52 ± 22.25
        GHS/HRQoL Scale Score, Week 42 (n=54, 14)
    6.17 ± 24.98
    1.19 ± 19.02
        GHS/HRQoL Scale Score, Week 48 (n=44, 12)
    6.44 ± 27.37
    4.86 ± 15.67
        GHS/HRQoL Scale Score, Week 57 (n=37, 8)
    8.56 ± 20.46
    8.33 ± 12.60
        GHS/HRQoL Scale Score, Week 66 (n=33, 5)
    6.82 ± 19.15
    5.00 ± 17.28
        GHS/HRQoL Scale Score, Week 75 (n=26, 4)
    3.85 ± 21.11
    2.08 ± 24.88
        GHS/HRQoL Scale Score, Week 84 (n=19, 3)
    11.40 ± 20.07
    -2.78 ± 12.73
        GHS/HRQoL Scale Score, Week 93 (n=20, 2)
    2.08 ± 24.61
    -12.50 ± 5.89
        GHS/HRQoL Scale Score, Week 102 (n=16, 1)
    4.69 ± 18.50
    -25.00 ± 99999
        GHS/HRQoL Scale Score, Week 111 (n=14, 0)
    1.79 ± 21.73
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 120 (n=14, 0)
    2.38 ± 20.52
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 129 (n=14, 0)
    -2.98 ± 19.78
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 138 (n=14, 0)
    1.19 ± 25.91
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 147 (n=14, 0)
    4.17 ± 18.42
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 156 (n=7, 0)
    -2.38 ± 17.82
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 165 (n=8, 0)
    -3.13 ± 23.54
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 174 (n=7, 0)
    -2.38 ± 17.82
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 183 (n=5, 0)
    -6.67 ± 19.00
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 192 (n=4, 0)
    -4.17 ± 20.97
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        GHS/HRQoL Scale Score, Week 210 (n=1, 0)
    -16.67 ± 99999
    00000 ± 00000
        GHS/HRQoL Scale Score, SFUV (n=11, 13)
    -9.85 ± 24.10
    3.85 ± 20.30
        Physical Functioning, Baseline (n=294, 146)
    61.34 ± 25.66
    61.97 ± 23.75
        Physical Functioning, Week 6 (n=221, 115)
    -2.93 ± 17.69
    -1.07 ± 18.49
        Physical Functioning, Week 12 (n=149, 64)
    0.17 ± 20.35
    1.46 ± 18.07
        Physical Functioning, Week 18 (n=121, 39)
    3.02 ± 17.97
    -1.58 ± 18.00
        Physical Functioning, Week 24 (n=107, 30)
    3.49 ± 18.66
    -5.50 ± 15.64
        Physical Functioning, Week 30 (n=84, 23)
    4.25 ± 18.22
    -1.23 ± 21.80
        Physical Functioning, Week 36 (n=63, 16)
    6.98 ± 19.68
    -4.90 ± 28.33
        Physical Functioning, Week 42 (n=54, 14)
    3.58 ± 24.08
    0.95 ± 16.92
        Physical Functioning, Week 48 (n=43, 12)
    7.44 ± 18.92
    2.22 ± 19.76
        Physical Functioning, Week 57 (n=36, 8)
    7.59 ± 16.73
    -3.33 ± 20.47
        Physical Functioning, Week 66 (n=33, 5)
    4.65 ± 22.39
    2.67 ± 17.38
        Physical Functioning, Week 75 (n=26, 4)
    4.87 ± 27.88
    -1.67 ± 34.16
        Physical Functioning, Week 84 (n=18, 3)
    3.70 ± 23.68
    -8.89 ± 26.94
        Physical Functioning, Week 93 (n=20, 2)
    1.67 ± 23.38
    -26.67 ± 18.86
        Physical Functioning, Week 102 (n=16, 1)
    2.40 ± 16.19
    -40.00 ± 99999
        Physical Functioning, Week 111 (n=14, 0)
    2.38 ± 19.67
    00000 ± 00000
        Physical Functioning, Week 120 (n=14, 0)
    3.33 ± 20.04
    00000 ± 00000
        Physical Functioning, Week 129 (n=13, 0)
    -1.03 ± 19.02
    00000 ± 00000
        Physical Functioning, Week 138 (n=14, 0)
    -0.48 ± 19.47
    00000 ± 00000
        Physical Functioning, Week 147 (n=14, 0)
    -0.48 ± 17.04
    00000 ± 00000
        Physical Functioning, Week 156 (n=7, 0)
    -4.76 ± 10.69
    00000 ± 00000
        Physical Functioning, Week 165 (n=8, 0)
    -3.61 ± 13.44
    00000 ± 00000
        Physical Functioning, Week 174 (n=7, 0)
    -1.90 ± 21.33
    00000 ± 00000
        Physical Functioning, Week 183 (n=5, 0)
    2.67 ± 19.21
    00000 ± 00000
        Physical Functioning, Week 192 (n=4, 0)
    -3.33 ± 12.77
    00000 ± 00000
        Physical Functioning, Week 201
    -3.33 ± 4.71
    00000 ± 00000
        Physical Functioning, Week 210 (n=2, 0)
    -20.00 ± 99999
    00000 ± 00000
        Physical Functioning, SFUV (n=1, 0)
    -9.70 ± 25.01
    -6.67 ± 27.08
        Role Functioning, Baseline (n=294, 145)
    62.53 ± 33.17
    61.72 ± 34.31
        Role Functioning, Week 6 (n=222, 114)
    -2.63 ± 28.13
    -3.51 ± 30.12
        Role Functioning, Week 12 (n=150, 63)
    -1.78 ± 30.48
    -1.59 ± 26.56
        Role Functioning, Week 18 (n=122, 39)
    -0.96 ± 30.02
    1.71 ± 36.63
        Role Functioning, Week 24 (n=107, 30)
    1.25 ± 30.00
    -5.00 ± 28.42
        Role Functioning, Week 30 (n=84, 23)
    -0.20 ± 29.10
    -7.25 ± 32.50
        Role Functioning, Week 36 (n=62, 16)
    2.15 ± 35.00
    -14.58 ± 47.09
        Role Functioning, Week 42 (n=54, 14)
    1.54 ± 35.95
    -4.76 ± 47.78
        Role Functioning, Week 48 (n=44, 12)
    4.92 ± 29.55
    -2.78 ± 34.69
        Role Functioning, Week 57 (n=37, 8)
    3.15 ± 28.82
    -4.17 ± 19.42
        Role Functioning, Week 66 (n=33, 5)
    0.51 ± 25.17
    -6.67 ± 25.28
        Role Functioning, Week 75 (n=26, 4)
    -0.64 ± 31.44
    8.33 ± 48.11
        Role Functioning, Week 84 (n=18, 3)
    3.70 ± 16.72
    -11.11 ± 19.25
        Role Functioning, Week 93 (n=20, 2)
    -1.67 ± 26.98
    -25.00 ± 35.36
        Role Functioning, Week 102 (n=16, 1)
    2.08 ± 18.13
    -33.33 ± 99999
        Role Functioning, Week 111 (n=14, 0)
    -3.57 ± 22.81
    00000 ± 00000
        Role Functioning, Week 120 (n=14, 0)
    -1.19 ± 19.02
    00000 ± 00000
        Role Functioning, Week 129 (n=14, 0)
    -1.19 ± 17.86
    00000 ± 00000
        Role Functioning, Week 138 (n=14, 0)
    -2.38 ± 22.51
    00000 ± 00000
        Role Functioning, Week 147 (n=14, 0)
    -3.57 ± 17.52
    00000 ± 00000
        Role Functioning, Week 156 (n=7, 0)
    -2.38 ± 6.30
    00000 ± 00000
        Role Functioning, Week 165 (n=8, 0)
    -10.42 ± 26.63
    00000 ± 00000
        Role Functioning, Week 174 (n=7, 0)
    -7.14 ± 26.97
    00000 ± 00000
        Role Functioning, Week 183 (n=5, 0)
    -10.00 ± 9.13
    00000 ± 00000
        Role Functioning, Week 192 (n=4, 0)
    -16.67 ± 13.61
    00000 ± 00000
        Role Functioning, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Role Functioning, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Role Functioning, SFUV (n=11, 13)
    -22.73 ± 41.01
    -1.28 ± 43.28
        Emotional Functioning, Baseline (n=290, 146)
    74.20 ± 23.87
    73.38 ± 23.55
        Emotional Functioning, Week 6 (n=219, 115)
    2.12 ± 20.59
    0.46 ± 23.00
        Emotional Functioning, Week 12 (n=148, 64)
    1.24 ± 21.06
    4.21 ± 22.77
        Emotional Functioning, Week 18 (n=120, 40)
    3.82 ± 18.23
    0.28 ± 22.10
        Emotional Functioning, Week 24 (n=105, 30)
    4.13 ± 17.07
    4.07 ± 17.40
        Emotional Functioning, Week 30 (n=83, 23)
    3.15 ± 17.62
    2.17 ± 20.29
        Emotional Functioning, Week 36 (n=62, 16)
    2.02 ± 16.78
    -5.38 ± 21.31
        Emotional Functioning, Week 42 (n=54, 14)
    2.01 ± 19.08
    -7.14 ± 16.30
        Emotional Functioning, Week 48 (n=43, 12)
    5.04 ± 13.87
    -3.47 ± 10.33
        Emotional Functioning, Week 57 (n=37, 8)
    5.78 ± 20.58
    3.13 ± 23.12
        Emotional Functioning, Week 66 (n=33, 5)
    4.29 ± 17.81
    6.67 ± 6.97
        Emotional Functioning, Week 75 (n=26, 4)
    0.32 ± 21.01
    12.50 ± 28.46
        Emotional Functioning, Week 84 (n=19, 3)
    6.58 ± 17.91
    0.00 ± 16.97
        Emotional Functioning, Week 93 (n=20, 2)
    2.92 ± 13.59
    -4.17 ± 5.89
        Emotional Functioning, Week 102 (n=16, 1)
    4.69 ± 12.53
    -16.67 ± 99999
        Emotional Functioning, Week 111 (n=14, 0)
    3.57 ± 15.92
    00000 ± 00000
        Emotional Functioning, Week 120 (n=14, 0)
    1.79 ± 10.93
    00000 ± 00000
        Emotional Functioning, Week 129 (n=14, 0)
    2.98 ± 12.91
    00000 ± 00000
        Emotional Functioning, Week 138 (n=14, 0)
    4.17 ± 12.97
    00000 ± 00000
        Emotional Functioning, Week 147 (n=14, 0)
    5.36 ± 18.08
    00000 ± 00000
        Emotional Functioning, Week 156 (n=7, 0)
    2.38 ± 10.45
    00000 ± 00000
        Emotional Functioning, Week 165 (n=8, 0)
    -1.04 ± 8.26
    00000 ± 00000
        Emotional Functioning, Week 174 (n=7, 0)
    2.38 ± 12.47
    00000 ± 00000
        Emotional Functioning, Week 183 (n=5, 0)
    -1.67 ± 10.87
    00000 ± 00000
        Emotional Functioning, Week 192 (n=4, 0)
    -2.08 ± 10.49
    00000 ± 00000
        Emotional Functioning, Week 201 (n=2, 0)
    -4.17 ± 17.68
    00000 ± 00000
        Emotional Functioning, Week 210 (n=1, 0)
    -16.67 ± 99999
    00000 ± 00000
        Emotional Functioning, SFUV (n=11, 13)
    6.82 ± 26.57
    -5.77 ± 21.08
        Cognitive Functioning, Baseline (n=291, 146)
    81.39 ± 21.49
    82.65 ± 19.95
        Cognitive Functioning, Week 6 (n=219, 115)
    -1.67 ± 21.17
    -5.94 ± 21.76
        Cognitive Functioning, Week 12 (n=149, 64)
    -1.79 ± 22.52
    -2.60 ± 22.27
        Cognitive Functioning, Week 18 (n=121, 40)
    2.62 ± 19.95
    -7.92 ± 24.46
        Cognitive Functioning, Week 24 (n=105, 30)
    0.48 ± 18.41
    -10.00 ± 28.57
        Cognitive Functioning, Week 30 (n=83, 23)
    -2.01 ± 18.11
    -8.70 ± 17.31
        Cognitive Functioning, Week 36 (n=62, 16)
    -0.54 ± 15.96
    -11.46 ± 16.91
        Cognitive Functioning, Week 42 (n=54, 14)
    -4.94 ± 23.71
    -7.14 ± 12.60
        Cognitive Functioning, Week 48 (n=44, 12)
    -1.89 ± 16.16
    -11.11 ± 14.79
        Cognitive Functioning, Week 57 (n=37, 8)
    -3.15 ± 20.73
    -2.08 ± 16.52
        Cognitive Functioning, Week 66 (n=33, 5)
    -4.04 ± 23.58
    -3.33 ± 18.26
        Cognitive Functioning, Week 75 (n=26, 4)
    -5.13 ± 17.49
    -4.17 ± 20.97
        Cognitive Functioning, Week 84 (n=19, 3)
    -3.51 ± 18.90
    5.56 ± 9.62
        Cognitive Functioning, Week 93 (n=20, 2)
    3.33 ± 12.80
    0.00 ± 0.00
        Cognitive Functioning, Week 102 (n=16, 1)
    4.17 ± 16.67
    0.00 ± 99999
        Cognitive Functioning, Week 111 (n=14, 0)
    4.76 ± 16.57
    00000 ± 00000
        Cognitive Functioning, Week 120 (n=14, 0)
    0.00 ± 20.67
    00000 ± 00000
        Cognitive Functioning, Week 129 (n=14, 0)
    0.00 ± 13.07
    00000 ± 00000
        Cognitive Functioning, Week 138 (n=14, 0)
    -2.38 ± 20.52
    00000 ± 00000
        Cognitive Functioning, Week 147 (n=14, 0)
    1.19 ± 16.62
    00000 ± 00000
        Cognitive Functioning, Week 156 (n=7, 0)
    4.76 ± 12.60
    00000 ± 00000
        Cognitive Functioning, Week 165 (n=8, 0)
    6.25 ± 12.40
    00000 ± 00000
        Cognitive Functioning, Week 174 (n=7, 0)
    0.00 ± 9.62
    00000 ± 00000
        Cognitive Functioning, Week 183 (n=5, 0)
    3.33 ± 18.26
    00000 ± 00000
        Cognitive Functioning, Week 192 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Cognitive Functioning, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Cognitive Functioning, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Cognitive Functioning, SFUV (n=11, 13)
    -16.67 ± 23.57
    5.13 ± 25.81
        Social Functioning, Baseline (n=290, 146)
    71.32 ± 29.12
    74.43 ± 27.62
        Social Functioning, Week 6 (n=218, 115)
    1.30 ± 27.66
    -4.49 ± 28.30
        Social Functioning, Week 12 (n=148, 64)
    1.58 ± 27.93
    -4.17 ± 32.93
        Social Functioning, Week 18 (n=119, 40)
    5.60 ± 24.38
    -14.17 ± 31.93
        Social Functioning, Week 24 (n=105, 30)
    5.08 ± 24.91
    -11.11 ± 27.45
        Social Functioning, Week 30 (n=83, 23)
    4.82 ± 23.79
    -5.80 ± 36.10
        Social Functioning, Week 36 (n=61, 16)
    3.01 ± 27.97
    -14.58 ± 42.11
        Social Functioning, Week 42 (n=54, 14)
    -0.31 ± 26.79
    -7.14 ± 36.23
        Social Functioning, Week 48 (n=44, 12)
    1.89 ± 21.93
    -5.56 ± 28.72
        Social Functioning, Week 57 (n=37, 8)
    3.60 ± 29.17
    2.08 ± 30.13
        Social Functioning, Week 66 (n=33, 5)
    5.56 ± 26.90
    3.33 ± 29.81
        Social Functioning, Week 75 (n=26, 4)
    5.77 ± 23.07
    4.17 ± 34.36
        Social Functioning, Week 84 (n=19, 3)
    2.63 ± 21.70
    22.22 ± 25.46
        Social Functioning, Week 93 (n=20, 2)
    8.33 ± 16.67
    8.33 ± 11.79
        Social Functioning, Week 102 (n=16, 1)
    9.38 ± 17.18
    16.67 ± 99999
        Social Functioning, Week 111 (n=14, 0)
    2.38 ± 18.32
    00000 ± 00000
        Social Functioning, Week 120 (n=14, 0)
    7.14 ± 14.19
    00000 ± 00000
        Social Functioning, Week 129 (n=14, 0)
    -2.38 ± 30.56
    00000 ± 00000
        Social Functioning, Week 138 (n=14, 0)
    2.38 ± 20.52
    00000 ± 00000
        Social Functioning, Week 147 (n=14, 0)
    7.14 ± 16.94
    00000 ± 00000
        Social Functioning, Week 156 (n=7, 0)
    4.76 ± 15.85
    00000 ± 00000
        Social Functioning, Week 165 (n=8, 0)
    -6.25 ± 29.46
    00000 ± 00000
        Social Functioning, Week 174 (n=7, 0)
    7.14 ± 26.97
    00000 ± 00000
        Social Functioning, Week 183 (n=5, 0)
    6.67 ± 38.37
    00000 ± 00000
        Social Functioning, Week 192 (n=4, 0)
    -4.17 ± 28.46
    00000 ± 00000
        Social Functioning, Week 201 (n=2, 0)
    -25.00 ± 35.36
    00000 ± 00000
        Social Functioning, Week 210 (n=1, 0)
    -50.00 ± 99999
    00000 ± 00000
        Social Functioning, SFUV (n=11, 13)
    1.52 ± 46.22
    -12.82 ± 34.80
        Fatigue, Baseline (n=293, 146)
    41.62 ± 26.98
    42.62 ± 25.10
        Fatigue, Week 6 (n=221, 115)
    3.37 ± 23.32
    2.08 ± 23.71
        Fatigue, Week 12 (n=148, 64)
    0.53 ± 26.98
    -1.56 ± 22.99
        Fatigue, Week 18 (n=121, 40)
    -1.79 ± 22.11
    2.22 ± 18.69
        Fatigue, Week 24 (n=106, 30)
    -3.14 ± 25.82
    2.96 ± 21.43
        Fatigue, Week 30 (n=83, 23)
    -2.88 ± 22.98
    -3.38 ± 24.03
        Fatigue, Week 36 (n=63, 16)
    -4.06 ± 28.12
    4.86 ± 27.81
        Fatigue, Week 42 (n=54, 14)
    -2.67 ± 29.11
    3.17 ± 28.05
        Fatigue, Week 48 (n=43, 12)
    -6.72 ± 24.86
    1.85 ± 23.61
        Fatigue, Week 57 (n=37, 8)
    -3.30 ± 22.66
    1.39 ± 18.25
        Fatigue, Week 66 (n=33, 5)
    -2.53 ± 29.63
    -6.67 ± 12.67
        Fatigue, Week 75 (n=26, 4)
    -4.70 ± 22.26
    -8.33 ± 33.18
        Fatigue, Week 84 (n=18, 3)
    -6.79 ± 26.72
    22.22 ± 19.25
        Fatigue, Week 93 (n=20, 2)
    -5.56 ± 30.05
    22.22 ± 0.00
        Fatigue, Week 102 (n=16, 1)
    -5.56 ± 26.91
    33.33 ± 99999
        Fatigue, Week 111 (n=14, 0)
    -0.79 ± 33.32
    00000 ± 00000
        Fatigue, Week 120 (n=14, 0)
    -2.38 ± 28.30
    00000 ± 00000
        Fatigue, Week 129 (n=14, 0)
    -2.78 ± 18.33
    00000 ± 00000
        Fatigue, Week 138 (n=14, 0)
    -1.59 ± 26.10
    00000 ± 00000
        Fatigue, Week 147 (n=14, 0)
    -3.17 ± 25.94
    00000 ± 00000
        Fatigue, Week 156 (n=7, 0)
    -1.59 ± 14.95
    00000 ± 00000
        Fatigue, Week 165 (n=8, 0)
    1.39 ± 29.95
    00000 ± 00000
        Fatigue, Week 174 (n=7, 0)
    -4.76 ± 20.14
    00000 ± 00000
        Fatigue, Week 183 (n=5, 0)
    4.44 ± 26.76
    00000 ± 00000
        Fatigue, Week 192 (n=4, 0)
    5.56 ± 14.34
    00000 ± 00000
        Fatigue, Week 201 (n=2, 0)
    -5.56 ± 7.86
    00000 ± 00000
        Fatigue, Week 210 (n=1, 0)
    -11.11 ± 99999
    00000 ± 00000
        Fatigue, SFUV (n=11, 13)
    0.00 ± 31.82
    1.71 ± 33.59
        Nausea and Vomiting, Baseline (n=294, 146)
    8.28 ± 17.07
    7.99 ± 15.06
        Nausea and Vomiting, Week 6 (n=222, 115)
    0.90 ± 16.98
    1.01 ± 19.28
        Nausea and Vomiting, Week 12 (n=149, 64)
    1.12 ± 17.72
    3.65 ± 16.92
        Nausea and Vomiting, Week 18 (n=122, 40)
    -0.41 ± 15.67
    3.33 ± 18.18
        Nausea and Vomiting, Week 24 (n=107, 30)
    -1.87 ± 14.54
    3.33 ± 16.02
        Nausea and Vomiting, Week 30 (n=84, 23)
    -2.38 ± 16.39
    3.62 ± 10.0063
        Nausea and Vomiting, Week 36 (n=63, 16)
    2.12 ± 17.32
    3.13 ± 15.18
        Nausea and Vomiting, Week 42 (n=54, 14)
    1.54 ± 11.79
    3.57 ± 19.81
        Nausea and Vomiting, Week 48 (n=43, 12)
    -1.55 ± 15.78
    0.00 ± 20.10
        Nausea and Vomiting, Week 57 (n=37, 8)
    2.25 ± 11.89
    2.08 ± 18.77
        Nausea and Vomiting, Week 66 (n=33, 5)
    -1.01 ± 14.99
    -3.33 ± 7.45
        Nausea and Vomiting, Week 75 (n=26, 4)
    2.56 ± 9.06
    -4.17 ± 8.33
        Nausea and Vomiting, Week 84 (n=19, 3)
    0.88 ± 8.74
    0.00 ± 16.67
        Nausea and Vomiting, Week 93 (n=20, 2)
    -1.67 ± 5.13
    -8.33 ± 11.79
        Nausea and Vomiting, Week 102 (n=16, 1)
    -2.08 ± 5.69
    0.00 ± 99999
        Nausea and Vomiting, Week 111 (n=14, 0)
    4.76 ± 12.10
    00000 ± 00000
        Nausea and Vomiting, Week 120 (n=14, 0)
    -1.19 ± 7.91
    00000 ± 00000
        Nausea and Vomiting, Week 129 (n=14, 0)
    0.00 ± 6.54
    00000 ± 00000
        Nausea and Vomiting, Week 138 (n=14, 0)
    -2.38 ± 6.05
    00000 ± 00000
        Nausea and Vomiting, Week 147 (n=14, 0)
    -2.38 ± 6.05
    00000 ± 00000
        Nausea and Vomiting, Week 156 (n=7, 0)
    -2.38 ± 6.30
    00000 ± 00000
        Nausea and Vomiting, Week 165 (n=8, 0)
    -2.08 ± 5.89
    00000 ± 00000
        Nausea and Vomiting, Week 174 (n=7, 0)
    -2.38 ± 6.30
    00000 ± 00000
        Nausea and Vomiting, Week 183 (n=5, 0)
    -3.33 ± 7.45
    00000 ± 00000
        Nausea and Vomiting, Week 192 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Nausea and Vomiting, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Nausea and Vomiting, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Nausea and Vomiting, SFUV (n=11, 13)
    13.64 ± 42.04
    0.00 ± 33.33
        Pain, Baseline (n=294, 146)
    31.52 ± 29.67
    32.99 ± 29.06
        Pain, Week 6 (n=222, 115)
    -0.98 ± 25.27
    -1.01 ± 26.61
        Pain, Week 12 (n=149, 64)
    -3.58 ± 29.67
    -5.73 ± 27.09
        Pain, Week 18 (n=121, 40)
    -5.51 ± 30.38
    3.75 ± 31.23
        Pain, Week 24 (n=107, 30)
    -6.70 ± 30.01
    3.89 ± 23.44
        Pain, Week 30 (n=84, 23)
    -5.36 ± 30.30
    -9.42 ± 21.80
        Pain, Week 36 (n=63, 16)
    -7.41 ± 28.36
    3.13 ± 25.25
        Pain, Week 42 (n=54, 14)
    -5.25 ± 33.77
    -4.76 ± 33.61
        Pain, Week 48 (n=44, 12)
    -9.85 ± 30.57
    -11.11 ± 26.91
        Pain, Week 57 (n=37, 8)
    -7.21 ± 31.80
    -6.25 ± 25.10
        Pain, Week 66 (n=33, 5)
    -13.13 ± 30.26
    -20.00 ± 21.73
        Pain, Week 75 (n=26, 4)
    -5.77 ± 33.65
    0.00 ± 36.00
        Pain, Week 84 (n=19, 3)
    -15.79 ± 26.34
    -11.11 ± 19.25
        Pain, Week 93 (n=20, 2)
    -7.50 ± 27.29
    -16.67 ± 23.57
        Pain, Week 102 (n=16, 1)
    -17.71 ± 25.44
    -33.33 ± 99999
        Pain, Week 111 (n=14, 0)
    -14.29 ± 23.44
    00000 ± 00000
        Pain, Week 120 (n=14, 0)
    -15.48 ± 26.53
    00000 ± 00000
        Pain, Week 129 (n=14, 0)
    -10.71 ± 16.80
    00000 ± 00000
        Pain, Week 138 (n=14, 0)
    -15.48 ± 25.71
    00000 ± 00000
        Pain, Week 147 (n=14, 0)
    -13.10 ± 27.87
    00000 ± 00000
        Pain, Week 156 (n=7, 0)
    -14.29 ± 20.25
    00000 ± 00000
        Pain, Week 165 (n=8, 0)
    -10.42 ± 19.80
    00000 ± 00000
        Pain, Week 174 (n=7, 0)
    -11.90 ± 34.31
    00000 ± 00000
        Pain, Week 183 (n=5, 0)
    -13.33 ± 36.13
    00000 ± 00000
        Pain, Week 192 (n=4, 0)
    -12.50 ± 25.00
    00000 ± 00000
        Pain, Week 201 (n=2, 0)
    -25.00 ± 35.36
    00000 ± 00000
        Pain, Week 210 (n=1, 0)
    -16.67 ± 99999
    00000 ± 00000
        Pain, SFUV (n=11, 13)
    9.09 ± 26.21
    -7.69 ± 38.26
        Dyspnoea, Baseline (n=294, 145)
    36.17 ± 30.47
    39.31 ± 31.35
        Dyspnoea, Week 6 (n=220, 114)
    -1.36 ± 28.55
    -0.58 ± 29.74
        Dyspnoea, Week 12 (n=149, 64)
    0.45 ± 30.51
    -4.69 ± 27.13
        Dyspnoea, Week 18 (n=122, 40)
    -1.91 ± 26.87
    -3.33 ± 31.85
        Dyspnoea, Week 24 (n=106, 30)
    -5.03 ± 29.02
    -4.44 ± 29.99
        Dyspnoea, Week 30 (n=84, 23)
    -4.37 ± 28.24
    -8.70 ± 30.51
        Dyspnoea, Week 36 (n=62, 16)
    -6.99 ± 27.08
    0.00 ± 34.43
        Dyspnoea, Week 42 (n=54, 13)
    -8.64 ± 32.50
    -7.69 ± 19.97
        Dyspnoea, Week 48 (n=44, 11)
    -7.58 ± 30.38
    -3.03 ± 23.35
        Dyspnoea, Week 57 (n=37, 8)
    -9.01 ± 30.07
    -12.50 ± 24.80
        Dyspnoea, Week 66 (n=33, 5)
    -3.03 ± 30.46
    -20.00 ± 18.26
        Dyspnoea, Week 75 (n=26, 4)
    -5.13 ± 22.49
    -16.67 ± 19.25
        Dyspnoea, Week 84 (n=18, 3)
    -9.26 ± 25.06
    0.00 ± 0.00
        Dyspnoea, Week 93 (n=20, 2)
    0.00 ± 35.87
    -16.67 ± 23.57
        Dyspnoea, Week 102 (n=16, 1)
    4.17 ± 26.87
    0.00 ± 99999
        Dyspnoea, Week 111 (n=13, 0)
    -7.69 ± 33.76
    00000 ± 00000
        Dyspnoea, Week 120 (n=14, 0)
    0.00 ± 22.65
    00000 ± 00000
        Dyspnoea, Week 129 (n=14, 0)
    2.38 ± 24.33
    00000 ± 00000
        Dyspnoea, Week 138 (n=14, 0)
    -2.38 ± 27.62
    00000 ± 00000
        Dyspnoea, Week 147 (n=14, 0)
    -4.76 ± 22.10
    00000 ± 00000
        Dyspnoea, Week 156 (n=7, 0)
    0.00 ± 19.25
    00000 ± 00000
        Dyspnoea, Week 165 (n=8, 0)
    -4.17 ± 21.36
    00000 ± 00000
        Dyspnoea, Week 174 (n=7, 0)
    4.76 ± 23.00
    00000 ± 00000
        Dyspnoea, Week 183 (n=5, 0)
    6.67 ± 27.89
    00000 ± 00000
        Dyspnoea, Week 192 (n=4, 0)
    0.00 ± 27.22
    00000 ± 00000
        Dyspnoea, Week 201 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Dyspnoea, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Dyspnoea, SFUV (n=11, 12)
    24.24 ± 44.95
    -2.78 ± 43.71
        Insomnia, Baseline (n=294, 146)
    30.50 ± 29.97
    31.05 ± 32.44
        Insomnia, Week 6 (n=222, 115)
    -1.95 ± 31.25
    -1.16 ± 33.60
        Insomnia, Week 12 (n=150, 64)
    -1.78 ± 31.32
    -3.65 ± 33.13
        Insomnia, Week 18 (n=122, 40)
    -4.37 ± 27.76
    -2.50 ± 36.51
        Insomnia, Week 24 (n=107, 30)
    -6.23 ± 29.01
    -5.56 ± 31.66
        Insomnia, Week 30 (n=84, 23)
    -3.17 ± 26.19
    -15.94 ± 28.19
        Insomnia, Week 36 (n=63, 16)
    -3.17 ± 26.58
    -18.75 ± 34.36
        Insomnia, Week 42 (n=54, 14)
    -3.09 ± 36.21
    -9.52 ± 27.51
        Insomnia, Week 48 (n=43, 12)
    -6.20 ± 27.46
    2.78 ± 26.43
        Insomnia, Week 57 (n=37, 8)
    -9.91 ± 32.27
    4.17 ± 33.03
        Insomnia, Week 66 (n=33, 5)
    -8.08 ± 27.68
    -6.67 ± 14.91
        Insomnia, Week 75 (n=26, 4)
    -8.97 ± 27.58
    -16.67 ± 19.25
        Insomnia, Week 84 (n=18, 3)
    -7.41 ± 24.40
    -22.22 ± 19.25
        Insomnia, Week 93 (n=20, 2)
    -8.33 ± 23.88
    0.00 ± 0.00
        Insomnia, Week 102 (n=16, 1)
    -10.42 ± 20.07
    0.00 ± 99999
        Insomnia, Week 111 (n=14, 0)
    -9.52 ± 20.37
    00000 ± 00000
        Insomnia, Week 120 (n=14, 0)
    -11.90 ± 21.11
    00000 ± 00000
        Insomnia, Week 129 (n=14, 0)
    -9.52 ± 20.37
    00000 ± 00000
        Insomnia, Week 138 (n=14, 0)
    -16.67 ± 21.68
    00000 ± 00000
        Insomnia, Week 147 (n=14, 0)
    -14.29 ± 28.39
    00000 ± 00000
        Insomnia, Week 156 (n=7, 0)
    -4.76 ± 12.60
    00000 ± 00000
        Insomnia, Week 165 (n=8, 0)
    0.00 ± 17.82
    00000 ± 00000
        Insomnia, Week 174 (n=7, 0)
    -9.52 ± 16.27
    00000 ± 00000
        Insomnia, Week 183 (n=5, 0)
    -13.33 ± 38.01
    00000 ± 00000
        Insomnia, Week 192 (n=4, 0)
    -8.33 ± 16.67
    00000 ± 00000
        Insomnia, Week 201 (n=2, 0)
    -33.33 ± 47.14
    00000 ± 00000
        Insomnia, Week 210 (n=1, 0)
    -33.33 ± 99999
    00000 ± 00000
        Insomnia, SFUV (n=11, 13)
    12.12 ± 42.88
    -5.13 ± 35.61
        Appetite Loss, Baseline (n=294, 146)
    31.63 ± 33.06
    31.05 ± 32.91
        Appetite Loss, Week 6 (n=221, 114)
    1.06 ± 33.99
    0.00 ± 38.40
        Appetite Loss, Week 12 (n=150, 64)
    -4.22 ± 35.46
    7.29 ± 32.24
        Appetite Loss, Week 18 (n=122, 40)
    -7.38 ± 33.06
    13.33 ± 27.01
        Appetite Loss, Week 24 (n=106, 30)
    -9.43 ± 28.27
    10.00 ± 32.93
        Appetite Loss, Week 30 (n=84, 23)
    -12.30 ± 28.24
    7.25 ± 31.71
        Appetite Loss, Week 36 (n=63, 16)
    -11.11 ± 33.87
    6.25 ± 30.35
        Appetite Loss, Week 42 (n=54, 14)
    -7.41 ± 32.81
    2.38 ± 27.62
        Appetite Loss, Week 48 (n=43, 12)
    -10.85 ± 29.74
    5.56 ± 44.57
        Appetite Loss, Week 57 (n=37, 8)
    -6.31 ± 31.27
    8.33 ± 42.72
        Appetite Loss, Week 66 (n=33, 5)
    -9.09 ± 29.19
    13.33 ± 29.81
        Appetite Loss, Week 75 (n=26, 4)
    -10.26 ± 30.94
    0.00 ± 27.22
        Appetite Loss, Week 84 (n=19, 3)
    -17.54 ± 28.04
    22.22 ± 19.25
        Appetite Loss, Week 93 (n=20, 2)
    -10.00 ± 26.71
    50.00 ± 23.57
        Appetite Loss, Week 102 (n=16, 1)
    -10.42 ± 20.07
    66.67 ± 99999
        Appetite Loss, Week 111 (n=14, 0)
    -7.14 ± 23.31
    00000 ± 00000
        Appetite Loss, Week 120 (n=14, 0)
    -9.52 ± 27.51
    00000 ± 00000
        Appetite Loss, Week 129 (n=14, 0)
    -7.14 ± 23.31
    00000 ± 00000
        Appetite Loss, Week 138 (n=14, 0)
    -9.52 ± 24.21
    00000 ± 00000
        Appetite Loss, Week 147 (n=14, 0)
    -16.67 ± 31.35
    00000 ± 00000
        Appetite Loss, Week 156 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Appetite Loss, Week 165 (n=8, 0)
    0.00 ± 0.00
    00000 ± 00000
        Appetite Loss, Week 174 (n=7, 0)
    -9.52 ± 25.20
    00000 ± 00000
        Appetite Loss, Week 183 (n=5, 0)
    -13.33 ± 29.81
    00000 ± 00000
        Appetite Loss, Week 192 (n=4, 0)
    8.33 ± 16.67
    00000 ± 00000
        Appetite Loss, Week 201 (n=2, 0)
    16.67 ± 23.57
    00000 ± 00000
        Appetite Loss, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Appetite Loss, SFUV (n=11, 13)
    -9.09 ± 39.70
    -7.69 ± 52.97
        Constipation, Baseline (n=294, 146)
    21.20 ± 30.67
    21.92 ± 27.80
        Constipation, Week 6 (n=221, 115)
    -0.45 ± 27.98
    1.45 ± 31.65
        Constipation, Week 12 (n=149, 64)
    -2.46 ± 29.79
    -0.52 ± 28.17
        Constipation, Week 18 (n=122, 40)
    -6.01 ± 29.39
    0.83 ± 29.71
        Constipation, Week 24 (n=107, 30)
    -5.61 ± 29.13
    1.11 ± 22.29
        Constipation, Week 30 (n=84, 23)
    -6.75 ± 27.76
    5.80 ± 25.92
        Constipation, Week 36 (n=63, 16)
    -7.94 ± 33.18
    6.25 ± 18.13
        Constipation, Week 42 (n=54, 14)
    -4.94 ± 31.33
    0.00 ± 18.49
        Constipation, Week 48 (n=44, 11)
    -10.61 ± 32.76
    -6.06 ± 25.03
        Constipation, Week 57 (n=37, 8)
    -15.32 ± 28.97
    -8.33 ± 15.43
        Constipation, Week 66 (n=33, 5)
    -13.13 ± 27.56
    0.00 ± 23.57
        Constipation, Week 75 (n=26, 4)
    -5.13 ± 32.24
    16.67 ± 57.74
        Constipation, Week 84 (n=19, 3)
    -3.51 ± 31.22
    11.11 ± 38.49
        Constipation, Week 93 (n=20, 2)
    -8.33 ± 35.66
    33.33 ± 0.00
        Constipation, Week 102 (n=16, 1)
    -10.42 ± 35.94
    33.33 ± 99999
        Constipation, Week 111 (n=14, 0)
    -7.14 ± 41.71
    00000 ± 00000
        Constipation, Week 120 (n=14, 0)
    -4.76 ± 41.05
    00000 ± 00000
        Constipation, Week 129 (n=14, 0)
    -7.14 ± 41.71
    00000 ± 00000
        Constipation, Week 138 (n=14, 0)
    -9.52 ± 47.91
    00000 ± 00000
        Constipation, Week 147 (n=14, 0)
    -11.90 ± 42.58
    00000 ± 00000
        Constipation, Week 156 (n=7, 0)
    -14.29 ± 26.23
    00000 ± 00000
        Constipation, Week 165 (n=8, 0)
    -8.33 ± 29.55
    00000 ± 00000
        Constipation, Week 174 (n=7, 0)
    -14.29 ± 26.23
    00000 ± 00000
        Constipation, Week 183 (n=5, 0)
    -13.33 ± 18.26
    00000 ± 00000
        Constipation, Week 192 (n=4, 0)
    0.00 ± 27.22
    00000 ± 00000
        Constipation, Week 201 (n=2, 0)
    16.67 ± 23.57
    00000 ± 00000
        Constipation, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Constipation, SFUV (n=11, 13)
    3.03 ± 45.84
    7.69 ± 30.89
        Diarrhoea, Baseline (n=290, 146)
    5.63 ± 15.28
    5.71 ± 16.31
        Diarrhoea, Week 6 (n=219, 115)
    -0.61 ± 19.93
    3.48 ± 23.93
        Diarrhoea, Week 12 (n=148, 63)
    1.80 ± 21.57
    1.06 ± 18.90
        Diarrhoea, Week 18 (n=120, 40)
    -0.83 ± 18.57
    5.83 ± 24.91
        Diarrhoea, Week 24 (n=104, 30)
    0.00 ± 18.58
    5.56 ± 17.69
        Diarrhoea, Week 30 (n=83, 23)
    2.01 ± 19.02
    4.35 ± 11.48
        Diarrhoea, Week 36 (n=62, 16)
    0.00 ± 20.91
    2.08 ± 8.33
        Diarrhoea, Week 42 (n=54, 14)
    -3.09 ± 17.46
    2.38 ± 8.91
        Diarrhoea, Week 48 (n=44, 12)
    -0.76 ± 15.23
    8.33 ± 20.72
        Diarrhoea, Week 57 (n=37, 8)
    0.00 ± 20.79
    4.17 ± 11.79
        Diarrhoea, Week 66 (n=33, 5)
    -4.04 ± 18.18
    6.67 ± 14.91
        Diarrhoea, Week 75 (n=26, 4)
    -5.13 ± 15.47
    0.00 ± 0.00
        Diarrhoea, Week 84 (n=19, 3)
    1.75 ± 13.49
    0.00 ± 0.00
        Diarrhoea, Week 93 (n=20, 2)
    1.67 ± 25.31
    0.00 ± 0.00
        Diarrhoea, Week 102 (n=16, 1)
    0.00 ± 17.21
    0.00 ± 99999
        Diarrhoea, Week 111 (n=14, 0)
    7.14 ± 29.75
    00000 ± 00000
        Diarrhoea, Week 120 (n=14, 0)
    4.76 ± 34.24
    00000 ± 00000
        Diarrhoea, Week 129 (n=14, 0)
    2.38 ± 33.24
    00000 ± 00000
        Diarrhoea, Week 138 (n=14, 0)
    -4.76 ± 17.82
    00000 ± 00000
        Diarrhoea, Week 147 (n=14, 0)
    -4.76 ± 22.10
    00000 ± 00000
        Diarrhoea, Week 156 (n=7, 0)
    -4.76 ± 12.60
    00000 ± 00000
        Diarrhoea, Week 165 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Diarrhoea, Week 174 (n=7, 0)
    -9.52 ± 25.20
    00000 ± 00000
        Diarrhoea, Week 183 (n=5, 0)
    -13.33 ± 29.81
    00000 ± 00000
        Diarrhoea, Week 192 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Diarrhoea, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Diarrhoea, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Diarrhoea, SFUV (n=11, 13)
    6.06 ± 29.13
    0.00 ± 13.61
        Financial Difficulties, Baseline (n=291, 146)
    22.22 ± 28.81
    20.32 ± 28.60
        Financial Difficulties, Week 6 (n=219, 115)
    -3.20 ± 27.00
    0.00 ± 25.74
        Financial Difficulties, Week 12 (n=148, 64)
    -4.95 ± 27.59
    1.56 ± 26.18
        Financial Difficulties, Week 18 (n=121, 40)
    -4.41 ± 23.94
    4.17 ± 27.41
        Financial Difficulties, Week 24 (n=105, 30)
    -4.76 ± 30.11
    2.22 ± 23.05
        Financial Difficulties, Week 30 (n=83, 23)
    -3.21 ± 24.20
    -1.45 ± 23.52
        Financial Difficulties, Week 36 (n=62, 15)
    -2.69 ± 28.50
    4.44 ± 21.33
        Financial Difficulties, Week 42 (n=54, 14)
    -1.85 ± 33.28
    2.38 ± 27.62
        Financial Difficulties, Week 48 (n=44, 12)
    -0.76 ± 29.19
    -5.56 ± 27.83
        Financial Difficulties, Week 57 (n=37, 8)
    -4.50 ± 32.55
    -4.17 ± 21.36
        Financial Difficulties, Week 66 (n=33, 5)
    0.00 ± 28.87
    -6.67 ± 27.89
        Financial Difficulties, Week 75 (n=26, 4)
    1.28 ± 29.03
    8.33 ± 31.91
        Financial Difficulties, Week 84 (n=19, 3)
    3.51 ± 26.98
    -22.22 ± 19.25
        Financial Difficulties, Week 93 (n=20, 2)
    0.00 ± 26.49
    -16.67 ± 23.57
        Financial Difficulties, Week 102 (n=16, 1)
    2.08 ± 25.73
    -33.33 ± 99999
        Financial Difficulties, Week 111 (n=14, 0)
    2.38 ± 27.62
    00000 ± 00000
        Financial Difficulties, Week 120 (n=14, 0)
    -2.38 ± 27.62
    00000 ± 00000
        Financial Difficulties, Week 129 (n=14, 0)
    -2.38 ± 24.33
    00000 ± 00000
        Financial Difficulties, Week 138 (n=14, 0)
    2.38 ± 30.56
    00000 ± 00000
        Financial Difficulties, Week 147 (n=14, 0)
    -2.38 ± 27.62
    00000 ± 00000
        Financial Difficulties, Week 156 (n=7, 0)
    -9.52 ± 31.71
    00000 ± 00000
        Financial Difficulties, Week 165 (n=8, 0)
    4.17 ± 37.53
    00000 ± 00000
        Financial Difficulties, Week 174 (n=7, 0)
    -9.52 ± 31.71
    00000 ± 00000
        Financial Difficulties, Week 183 (n=5, 0)
    0.00 ± 23.57
    00000 ± 00000
        Financial Difficulties, Week 192 (n=4, 0)
    0.00 ± 27.22
    00000 ± 00000
        Financial Difficulties, Week 201 (n=2, 0)
    16.67 ± 23.57
    00000 ± 00000
        Financial Difficulties, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Financial Difficulties, SFUV (n=11, 13)
    -3.03 ± 43.34
    0.00 ± 27.22
    No statistical analyses for this end point

    Secondary: Percentage of Participants With At Lease One Adverse Events (AEs)

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    End point title
    		 Percentage of Participants With At Lease One Adverse Events (AEs)
    End point description
    Percentage of participants with at least one adverse event.
    End point type
    Secondary
    End point timeframe
    From randomization up to approximately 55 months
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    300
    147
    Units: Percentage of participants
        number (not applicable)
    91.7
    97.3
    No statistical analyses for this end point

    Secondary: Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score

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    End point title
    		 Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score
    End point description
    The EORTC QLQ-LC13 module incorporates one multiple item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A≥10-point change in the symptoms subscale score is perceived by participants as clinically significant (Osoba et al. 1998). '99999'=standard deviation (SD) non-estimable due to 1 participant evaluated. '00000'=data not reported due to no participant evaluated.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    302
    151
    Units: units of a scale
    arithmetic mean (standard deviation)
        Dyspnoea, Baseline (n=287, 140)
    34.30 ± 25.69
    36.67 ± 25.35
        Dyspnoea, Week 6 (n=207, 109)
    1.13 ± 19.90
    0.92 ± 24.25
        Dyspnoea, Week 12 (n=144, 62)
    -0.23 ± 24.28
    -2.87 ± 24.55
        Dyspnoea, Week 18 (n=114, 37)
    -4.78 ± 18.93
    0.90 ± 23.33
        Dyspnoea, Week 24 (n=99, 29)
    -5.05 ± 22.91
    2.68 ± 23.13
        Dyspnoea, Week 30 (n=79, 22)
    -5.34 ± 22.00
    1.52 ± 25.03
        Dyspnoea, Week 36 (n=57, 14)
    -3.90 ± 26.85
    5.56 ± 19.85
        Dyspnoea, Week 42 (n=48, 13)
    -11.11 ± 26.63
    -6.84 ± 22.01
        Dyspnoea, Week 48 (n=39, 12)
    -4.84 ± 26.83
    1.85 ± 22.64
        Dyspnoea, Week 57 (n=31, 8)
    -7.89 ± 20.53
    4.17 ± 15.64
        Dyspnoea, Week 66 (n=27, 5)
    -6.58 ± 24.12
    0.00 ± 13.61
        Dyspnoea, Week 75 (n=22, 4)
    -4.55 ± 23.67
    -2.78 ± 30.60
        Dyspnoea, Week 84 (n=17, 3)
    -8.50 ± 23.74
    3.70 ± 23.13
        Dyspnoea, Week 93 (n=19, 2)
    -2.34 ± 27.61
    5.56 ± 7.86
        Dyspnoea, Week 102 (n=15, 1)
    -2.96 ± 21.19
    0.00 ± 99999
        Dyspnoea, Week 111 (n=13, 0)
    -2.56 ± 26.51
    00000 ± 00000
        Dyspnoea, Week 120 (n=13, 0)
    -4.27 ± 24.23
    00000 ± 00000
        Dyspnoea, Week 129 (n=12, 0)
    3.70 ± 15.95
    00000 ± 00000
        Dyspnoea, Week 138 (n=13, 0)
    0.00 ± 24.43
    00000 ± 00000
        Dyspnoea, Week 147 (n=13, 0)
    -0.85 ± 26.24
    00000 ± 00000
        Dyspnoea, Week 156 (n=7, 0)
    1.59 ± 14.95
    00000 ± 00000
        Dyspnoea, Week 165 (n=6, 0)
    -1.85 ± 21.56
    00000 ± 00000
        Dyspnoea, Week 174 (n=7, 0)
    1.59 ± 17.48
    00000 ± 00000
        Dyspnoea, Week 183 (n=4, 0)
    5.56 ± 21.28
    00000 ± 00000
        Dyspnoea, Week 192 (n=4, 0)
    5.56 ± 26.45
    00000 ± 00000
        Dyspnoea, Week 201 (n=2, 0)
    0.00 ± 15.71
    00000 ± 00000
        Dyspnoea, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Dyspnoea, Safety Follow-Up Visit (n=11, 12)
    12.12 ± 29.17
    6.48 ± 31.94
        Coughing, Baseline (n=295, 147)
    41.36 ± 30.24
    46.26 ± 28.25
        Coughing, Week 6 (n=222, 116)
    -1.80 ± 25.10
    -5.46 ± 29.80
        Coughing, Week 12 (n=149, 64)
    -7.61 ± 30.79
    -9.38 ± 29.97
        Coughing, Week 18 (n=121, 39)
    -9.64 ± 29.01
    -3.42 ± 34.87
        Coughing, Week 24 (n=106, 30)
    -11.01 ± 30.42
    3.33 ± 30.76
        Coughing, Week 30 (n=83, 24)
    -9.24 ± 33.46
    0.00 ± 26.01
        Coughing, Week 36 (n=61, 16)
    -7.10 ± 35.02
    0.00 ± 34.43
        Coughing, Week 42 (n=53, 14)
    -10.06 ± 31.07
    -2.38 ± 27.62
        Coughing, Week 48 (n=44, 12)
    -15.91 ± 30.06
    0.00 ± 20.10
        Coughing, Week 57 (n=35, 8)
    -14.29 ± 31.61
    4.17 ± 27.82
        Coughing, Week 66 (n=32, 5)
    -11.46 ± 33.45
    -13.33 ± 18.26
        Coughing, Week 75 (n=25, 4)
    -9.33 ± 28.09
    -8.33 ± 16.67
        Coughing, Week 84 (n=19, 3)
    -19.30 ± 32.04
    11.11 ± 19.25
        Coughing, Week 93 (n=20, 2)
    -21.67 ± 31.11
    16.67 ± 23.57
        Coughing, Week 102 (n=16, 1)
    -14.58 ± 20.97
    0.00 ± 99999
        Coughing, Week 111 (n=14, 0)
    -11.90 ± 21.11
    00000 ± 00000
        Coughing, Week 120 (n=14, 0)
    -11.90 ± 21.11
    00000 ± 00000
        Coughing, Week 129 (n=14, 0)
    -14.29 ± 21.54
    00000 ± 00000
        Coughing, Week 138 (n=14, 0)
    -16.67 ± 21.68
    00000 ± 00000
        Coughing, Week 147 (n=14, 0)
    -21.43 ± 24.83
    00000 ± 00000
        Coughing, Week 156 (n=7, 0)
    -23.81 ± 31.71
    00000 ± 00000
        Coughing, Week 165 (n=8, 0)
    -16.67 ± 35.63
    00000 ± 00000
        Coughing, Week 174 (n=7, 0)
    -19.05 ± 32.53
    00000 ± 00000
        Coughing, Week 183 (n=4, 0)
    0.00 ± 27.22
    00000 ± 00000
        Coughing, Week 192 (n=4, 0)
    -16.67 ± 19.25
    00000 ± 00000
        Coughing, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Coughing, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Coughing, Safety Follow-Up Visit (n=11, 13)
    3.03 ± 37.87
    -17.95 ± 25.88
        Haemoptysis, Baseline (n=296, 146)
    5.86 ± 14.38
    7.76 ± 18.79
        Haemoptysis, Week 6 (n=223, 115)
    0.75 ± 19.10
    -4.64 ± 21.58
        Haemoptysis, Week 12 (n=148, 63)
    -1.80 ± 15.45
    -3.17 ± 20.49
        Haemoptysis, Week 18 (n=122, 39)
    -1.64 ± 15.95
    -1.71 ± 17.01
        Haemoptysis, Week 24 (n=106, 30)
    -2.52 ± 13.57
    -1.11 ± 18.54
        Haemoptysis, Week 30 (n=84, 23)
    -3.97 ± 14.08
    -2.90 ± 13.90
        Haemoptysis, Week 36 (n=60, 16)
    -1.67 ± 17.81
    -6.25 ± 18.13
        Haemoptysis, Week 42 (n=53, 14)
    -1.26 ± 15.96
    -2.38 ± 20.52
        Haemoptysis, Week 48 (n=44, 12)
    -3.79 ± 12.89
    -5.56 ± 19.25
        Haemoptysis, Week 57 (n=36, 8)
    -2.78 ± 18.47
    -8.33 ± 23.57
        Haemoptysis, Week 66 (n=31, 5)
    -2.15 ± 11.97
    0.00 ± 0.00
        Haemoptysis, Week 75 (n=25, 4)
    -1.33 ± 11.71
    0.00 ± 0.00
        Haemoptysis, Week 84 (n=19, 3)
    -3.51 ± 10.51
    0.00 ± 0.00
        Haemoptysis, Week 93 (n=20, 2)
    -1.67 ± 13.13
    0.00 ± 0.00
        Haemoptysis, Week 102 (n=16, 1)
    -2.08 ± 8.33
    0.00 ± 99999
        Haemoptysis, Week 111 (n=14, 0)
    -2.38 ± 8.91
    00000 ± 00000
        Haemoptysis, Week 120 (n=14, 0)
    -2.38 ± 8.91
    00000 ± 00000
        Haemoptysis, Week 129 (n=14, 0)
    -2.38 ± 8.91
    00000 ± 00000
        Haemoptysis, Week 138 (n=14, 0)
    -2.38 ± 8.91
    00000 ± 00000
        Haemoptysis, Week 147 (n=14, 0)
    -2.38 ± 8.91
    00000 ± 00000
        Haemoptysis, Week 156 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Haemoptysis, Week 165 (n=8, 0)
    0.00 ± 0.00
    00000 ± 00000
        Haemoptysis, Week 174 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Haemoptysis, Week 183 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Haemoptysis, Week 192 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Haemoptysis, Week 201 (n=14, 0)
    0.00 ± 0.00
    00000 ± 00000
        Haemoptysis, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Haemoptysis, Safety Follow-Up Visit (n=11, 13)
    3.03 ± 17.98
    -2.56 ± 16.45
        Sore Mouth, Baseline (n=296, 146)
    4.17 ± 13.50
    5.02 ± 14.83
        Sore Mouth, Week 6 (n=223, 115)
    1.64 ± 19.30
    0.00 ± 20.23
        Sore Mouth, Week 12 (n=150, 64)
    -0.22 ± 17.91
    0.00 ± 16.80
        Sore Mouth, Week 18 (n=122, 39)
    -0.82 ± 16.85
    2.56 ± 20.78
        Sore Mouth, Week 24 (n=105, 29)
    -1.90 ± 19.52
    2.30 ± 17.66
        Sore Mouth, Week 30 (n=84, 23)
    -3.57 ± 21.96
    0.00 ± 17.41
        Sore Mouth, Week 36 (n=61, 16)
    -2.73 ± 22.19
    -2.08 ± 19.12
        Sore Mouth, Week 42 (n=53, 14)
    0.00 ± 29.24
    4.76 ± 28.81
        Sore Mouth, Week 48 (n=44, 12)
    -5.30 ± 18.94
    -2.78 ± 22.29
        Sore Mouth, Week 57 (n=36, 8)
    -5.56 ± 20.31
    0.00 ± 17.82
        Sore Mouth, Week 66 (n=32, 5)
    -4.17 ± 16.40
    6.67 ± 14.91
        Sore Mouth, Week 75 (n=25, 4)
    -5.33 ± 15.75
    16.67 ± 19.25
        Sore Mouth, Week 84 (n=19, 3)
    -1.75 ± 7.65
    11.11 ± 19.25
        Sore Mouth, Week 93 (n=20, 2)
    -1.67 ± 7.45
    0.00 ± 0.00
        Sore Mouth, Week 102 (n=16, 1)
    2.08 ± 8.33
    0.00 ± 99999
        Sore Mouth, Week 111 (n=14, 0)
    0.00 ± 22.65
    00000 ± 00000
        Sore Mouth, Week 120 (n=14, 0)
    2.38 ± 8.91
    00000 ± 00000
        Sore Mouth, Week 129 (n=14, 0)
    -4.76 ± 17.82
    00000 ± 00000
        Sore Mouth, Week 138 (n=14, 0)
    2.38 ± 8.91
    00000 ± 00000
        Sore Mouth, Week 147 (n=14, 0)
    0.00 ± 0.00
    00000 ± 00000
        Sore Mouth, Week 156 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Sore Mouth, Week 165 (n=8, 0)
    4.17 ± 27.82
    00000 ± 00000
        Sore Mouth, Week 174 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Sore Mouth, Week 183 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Sore Mouth, Week 192 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Sore Mouth, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Sore Mouth, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Sore Mouth, Safety Follow-Up Visit (n=11, 13)
    27.27 ± 32.72
    0.00 ± 19.25
        Dysphagia, Baseline (n=296, 146)
    11.15 ± 23.60
    8.68 ± 19.60
        Dysphagia, Week 6 (n=223, 115)
    -1.20 ± 20.47
    2.90 ± 25.96
        Dysphagia, Week 12 (n=151, 64)
    -0.44 ± 21.77
    -1.04 ± 23.73
        Dysphagia, Week 18 (n=122, 39)
    -2.19 ± 23.37
    -0.85 ± 29.11
        Dysphagia, Week 24 (n=106, 30)
    -4.72 ± 23.20
    1.11 ± 28.34
        Dysphagia, Week 30 (n=84, 23)
    -3.57 ± 23.15
    2.90 ± 28.27
        Dysphagia, Week 36 (n=60, 16)
    -6.11 ± 28.45
    6.25 ± 13.44
        Dysphagia, Week 42 (n=53, 14)
    -7.55 ± 31.11
    4.76 ± 17.82
        Dysphagia, Week 48 (n=44, 12)
    -5.30 ± 23.78
    0.00 ± 14.21
        Dysphagia, Week 57 (n=36, 8)
    -3.70 ± 29.58
    4.17 ± 21.36
        Dysphagia, Week 66 (n=31, 5)
    -6.45 ± 32.68
    0.00 ± 0.00
        Dysphagia, Week 75 (n=25, 4)
    -4.00 ± 27.76
    16.67 ± 33.33
        Dysphagia, Week 84 (n=19, 3)
    -8.77 ± 33.04
    0.00 ± 0.00
        Dysphagia, Week 93 (n=20, 2)
    0.00 ± 28.61
    0.00 ± 0.00
        Dysphagia, Week 102 (n=16, 1)
    0.00 ± 0.00
    0.00 ± 99999
        Dysphagia, Week 111 (n=14, 0)
    -4.76 ± 22.10
    00000 ± 00000
        Dysphagia, Week 120 (n=14, 0)
    2.38 ± 8.91
    00000 ± 00000
        Dysphagia, Week 129 (n=14, 0)
    -2.38 ± 20.52
    00000 ± 00000
        Dysphagia, Week 138 (n=14, 0)
    4.76 ± 12.10
    00000 ± 00000
        Dysphagia, Week 147 (n=14, 0)
    -4.76 ± 28.81
    00000 ± 00000
        Dysphagia, Week 156 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Dysphagia, Week 165 (n=8, 0)
    -8.33 ± 23.57
    00000 ± 00000
        Dysphagia, Week 174 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Dysphagia, Week 183 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Dysphagia, Week 192 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Dysphagia, Week 201 (n=2, 0)
    16.67 ± 23.57
    00000 ± 00000
        Dysphagia, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Dysphagia, Safety Follow-Up Visit (n=11, 13)
    12.12 ± 37.34
    0.00 ± 19.25
        Peripheral Neuropathy, Baseline (n=296, 146)
    11.26 ± 21.10
    14.84 ± 24.46
        Peripheral Neuropathy, Week 6 (n=223, 115)
    3.29 ± 19.74
    1.45 ± 25.51
        Peripheral Neuropathy, Week 12 (n=151, 64)
    1.99 ± 21.16
    2.08 ± 26.48
        Peripheral Neuropathy, Week 18 (n=121, 39)
    1.10 ± 19.21
    5.13 ± 24.83
        Peripheral Neuropathy, Week 24 (n=106, 30)
    3.77 ± 23.60
    7.78 ± 22.63
        Peripheral Neuropathy, Week 30 (n=83, 23)
    4.82 ± 20.25
    -1.45 ± 21.27
        Peripheral Neuropathy, Week 36 (n=60, 16)
    7.78 ± 24.83
    12.50 ± 29.50
        Peripheral Neuropathy, Week 42 (n=53, 14)
    8.18 ± 23.48
    9.52 ± 20.37
        Peripheral Neuropathy, Week 48 (n=44, 12)
    6.82 ± 23.38
    8.33 ± 20.72
        Peripheral Neuropathy, Week 57 (n=36, 8)
    7.41 ± 25.34
    20.83 ± 30.54
        Peripheral Neuropathy, Week 66 (n=32, 5)
    6.25 ± 23.09
    13.33 ± 38.01
        Peripheral Neuropathy, Week 75 (n=25, 4)
    5.33 ± 22.93
    8.33 ± 31.91
        Peripheral Neuropathy, Week 84 (n=19, 3)
    8.77 ± 21.78
    0.00 ± 0.00
        Peripheral Neuropathy, Week 93 (n=20, 2)
    6.67 ± 17.44
    0.00 ± 0.00
        Peripheral Neuropathy, Week 102 (n=16, 1)
    6.25 ± 18.13
    0.00 ± 99999
        Peripheral Neuropathy, Week 111 (n=14, 0)
    2.38 ± 15.82
    00000 ± 00000
        Peripheral Neuropathy, Week 120 (n=14, 0)
    2.38 ± 15.82
    00000 ± 00000
        Peripheral Neuropathy, Week 129 (n=14, 0)
    2.38 ± 15.82
    00000 ± 00000
        Peripheral Neuropathy, Week 138 (n=14, 0)
    0.00 ± 13.07
    00000 ± 00000
        Peripheral Neuropathy, Week 147 (n=14, 0)
    2.38 ± 15.82
    00000 ± 00000
        Peripheral Neuropathy, Week 156 (n=7, 0)
    -4.76 ± 12.60
    00000 ± 00000
        Peripheral Neuropathy, Week 165 (n=8, 0)
    0.00 ± 17.82
    00000 ± 00000
        Peripheral Neuropathy, Week 174 (n=7, 0)
    -4.76 ± 12.60
    00000 ± 00000
        Peripheral Neuropathy, Week 183 (n=4, 0)
    -8.33 ± 16.67
    00000 ± 00000
        Peripheral Neuropathy, Week 192 (n=4, 0)
    16.67 ± 43.03
    00000 ± 00000
        Peripheral Neuropathy, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Peripheral Neuropathy, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Peripheral Neuropathy, SFUV (n=11, 12)
    21.21 ± 40.20
    -2.78 ± 33.21
        Alopecia, Baseline (n=295, 145)
    7.91 ± 20.70
    4.83 ± 15.70
        Alopecia, Week 6 (n=220, 115)
    -1.06 ± 19.48
    6.09 ± 27.07
        Alopecia, Week 12 (n=149, 63)
    -2.01 ± 17.43
    7.94 ± 27.90
        Alopecia, Week 18 (n=121, 39)
    -1.93 ± 17.90
    12.82 ± 23.71
        Alopecia, Week 24 (n=105, 28)
    -1.27 ± 17.86
    14.29 ± 30.67
        Alopecia, Week 30 (n=83, 23)
    -1.20 ± 19.79
    10.14 ± 27.40
        Alopecia, Week 36 (n=60, 16)
    5.56 ± 17.54
    10.42 ± 29.11
        Alopecia, Week 42 (n=52, 14)
    3.85 ± 14.24
    7.14 ± 29.75
        Alopecia, Week 48 (n=43, 12)
    3.10 ± 17.54
    13.89 ± 36.12
        Alopecia, Week 57 (n=35, 8)
    7.62 ± 18.23
    29.17 ± 27.82
        Alopecia, Week 66 (n=30, 5)
    6.67 ± 13.56
    6.67 ± 14.91
        Alopecia, Week 75 (n=24, 4)
    5.56 ± 12.69
    8.33 ± 16.67
        Alopecia, Week 84 (n=19, 3)
    1.75 ± 7.65
    11.11 ± 19.25
        Alopecia, Week 93 (n=20, 2)
    5.00 ± 12.21
    16.67 ± 23.57
        Alopecia, Week 102 (n=16, 1)
    4.17 ± 11.39
    33.33 ± 99999
        Alopecia, Week 111 (n=14, 0)
    2.38 ± 8.91
    00000 ± 00000
        Alopecia, Week 120 (n=14, 0)
    4.76 ± 12.10
    00000 ± 00000
        Alopecia, Week 129 (n=14, 0)
    2.38 ± 8.91
    00000 ± 00000
        Alopecia, Week 138 (n=14, 0)
    7.14 ± 19.30
    00000 ± 00000
        Alopecia, Week 147 (n=14, 0)
    2.38 ± 8.91
    00000 ± 00000
        Alopecia, Week 156 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Alopecia, Week 165 (n=8, 0)
    0.00 ± 0.00
    00000 ± 00000
        Alopecia, Week 174 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Alopecia, Week 183 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Alopecia, Week 192 (n=4, 0)
    8.33 ± 16.67
    00000 ± 00000
        Alopecia, Week 201 (n=2, 0)
    16.67 ± 23.57
    00000 ± 00000
        Alopecia, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Alopecia, SFUV (n=11, 13)
    0.00 ± 0.00
    12.82 ± 44.18
        Pain in Chest, Baseline (n=294, 144)
    20.29 ± 26.70
    19.91 ± 24.72
        Pain in Chest, Week 6 (n=218, 114)
    -2.45 ± 26.66
    -4.09 ± 29.79
        Pain in Chest, Week 12 (n=149, 63)
    -4.03 ± 27.65
    -5.29 ± 31.80
        Pain in Chest, Week 18 (n=121, 38)
    -9.37 ± 27.29
    -5.26 ± 26.31
        Pain in Chest, Week 24 (n=105, 29)
    -7.62 ± 28.22
    -2.30 ± 28.07
        Pain in Chest, Week 30 (n=83, 22)
    -7.23 ± 31.26
    -9.09 ± 34.40
        Pain in Chest, Week 36 (n=60, 14)
    -11.67 ± 29.96
    2.38 ± 30.56
        Pain in Chest, Week 42 (n=52, 13)
    -11.54 ± 34.86
    -2.56 ± 31.80
        Pain in Chest, Week 48 (n=43, 11)
    -17.83 ± 28.50
    3.03 ± 17.98
        Pain in Chest, Week 57 (n=35, 7)
    -18.10 ± 30.62
    -4.76 ± 23.00
        Pain in Chest, Week 66 (n=31, 4)
    -15.05 ± 34.25
    -16.67 ± 19.25
        Pain in Chest, Week 75 (n=24, 3)
    -13.89 ± 21.80
    -22.22 ± 19.25
        Pain in Chest, Week 84 (n=19, 2)
    -22.81 ± 31.53
    -16.67 ± 23.57
        Pain in Chest, Week 93 (n=20, 1)
    -23.33 ± 26.71
    0.00 ± 99999
        Pain in Chest, Week 102 (n=16, 0)
    -20.83 ± 31.91
    00000 ± 00000
        Pain in Chest, Week 111 (n=14, 0)
    -26.19 ± 29.75
    00000 ± 00000
        Pain in Chest, Week 120 (n=14, 0)
    -26.19 ± 29.75
    00000 ± 00000
        Pain in Chest, Week 129 (n=14, 0)
    -21.43 ± 21.11
    00000 ± 00000
        Pain in Chest, Week 138 (n=14, 0)
    -26.19 ± 29.75
    00000 ± 00000
        Pain in Chest, Week 147 (n=14, 0)
    -19.05 ± 36.31
    00000 ± 00000
        Pain in Chest, Week 156 (n=7, 0)
    -23.81 ± 25.20
    00000 ± 00000
        Pain in Chest, Week 165 (n=8, 0)
    -25.00 ± 23.57
    00000 ± 00000
        Pain in Chest, Week 174 (n=7, 0)
    -23.81 ± 25.20
    00000 ± 00000
        Pain in Chest, Week 183 (n=4, 0)
    -16.67 ± 33.33
    00000 ± 00000
        Pain in Chest, Week 192 (n=4, 0)
    -16.67 ± 33.33
    00000 ± 00000
        Pain in Chest, Week 201 (n=2, 0)
    -33.33 ± 47.14
    00000 ± 00000
        Pain in Chest, Week 210 (n=1, 0)
    -66.67 ± 99999
    00000 ± 00000
        Pain in Chest, SFUV (n=11, 13)
    0.00 ± 21.08
    12.82 ± 21.68
        Pain in Arm or Shoulder, Baseline (n=294, 145)
    19.16 ± 28.08
    19.08 ± 27.43
        Pain in Arm or Shoulder, Week 6 (n=221, 114)
    -0.45 ± 26.87
    -0.58 ± 29.07
        Pain in Arm or Shoulder, Week 12 (n=149, 63)
    0.67 ± 29.38
    -4.23 ± 30.81
        Pain in Arm or Shoulder, Week 18 (n=121, 38)
    -1.65 ± 30.08
    -2.63 ± 34.99
        Pain in Arm or Shoulder, Week 24 (n=104, 28)
    -3.21 ± 27.68
    0.00 ± 28.69
        Pain in Arm or Shoulder, Week 30 (n=83, 22)
    -0.40 ± 26.80
    4.55 ± 25.81
        Pain in Arm or Shoulder, Week 36 (n=60, 15)
    -4.44 ± 23.34
    -2.22 ± 34.43
        Pain in Arm or Shoulder, Week 42 (n=53, 13)
    -1.89 ± 25.67
    -5.13 ± 38.12
        Pain in Arm or Shoulder, Week 48 (n=44, 11)
    -1.52 ± 28.71
    -6.06 ± 35.96
        Pain in Arm or Shoulder, Week 57 (n=36, 7)
    7.41 ± 25.34
    -9.52 ± 37.09
        Pain in Arm or Shoulder, Week 66 (n=31, 4)
    1.08 ± 26.50
    -33.33 ± 38.49
        Pain in Arm or Shoulder, Week 75 (n=24, 3)
    -1.39 ± 26.88
    -33.33 ± 33.33
        Pain in Arm or Shoulder, Week 84 (n=19, 2)
    3.51 ± 24.58
    -16.67 ± 23.57
        Pain in Arm or Shoulder, Week 93 (n=20, 1)
    6.67 ± 23.20
    0.00 ± 99999
        Pain in Arm or Shoulder, Week 102 (n=16, 0)
    8.33 ± 25.82
    00000 ± 00000
        Pain in Arm or Shoulder, Week 111 (n=14, 0)
    2.38 ± 27.62
    00000 ± 00000
        Pain in Arm or Shoulder, Week 120 (n=14, 0)
    4.76 ± 25.68
    00000 ± 00000
        Pain in Arm or Shoulder, Week 129 (n=14, 0)
    2.38 ± 27.62
    00000 ± 00000
        Pain in Arm or Shoulder, Week 138 (n=14, 0)
    2.38 ± 24.33
    00000 ± 00000
        Pain in Arm or Shoulder, Week 147 (n=14, 0)
    2.38 ± 27.62
    00000 ± 00000
        Pain in Arm or Shoulder, Week 156 (n=7, 0)
    9.52 ± 16.27
    00000 ± 00000
        Pain in Arm or Shoulder, Week 165 (n=8, 0)
    4.17 ± 11.79
    00000 ± 00000
        Pain in Arm or Shoulder, Week 174 (n=7, 0)
    0.00 ± 0.00
    00000 ± 00000
        Pain in Arm or Shoulder, Week 183 (n=4, 0)
    25.00 ± 31.91
    00000 ± 00000
        Pain in Arm or Shoulder, Week 192 (n=4, 0)
    0.00 ± 0.00
    00000 ± 00000
        Pain in Arm or Shoulder, Week 201 (n=2, 0)
    0.00 ± 0.00
    00000 ± 00000
        Pain in Arm or Shoulder, Week 210 (n=1, 0)
    0.00 ± 99999
    00000 ± 00000
        Pain in Arm or Shoulder, SFUV (n=11, 13)
    12.12 ± 42.88
    7.69 ± 33.76
        Pain in other parts, Baseline (n=287, 144)
    25.32 ± 31.93
    27.55 ± 31.86
        Pain in other parts, Week 6 (n=216, 113)
    -1.85 ± 29.05
    1.18 ± 33.31
        Pain in other parts, Week 12 (n=147, 62)
    -0.91 ± 32.63
    -0.54 ± 34.93
        Pain in other parts, Week 18 (n=115, 36)
    -1.74 ± 36.63
    11.11 ± 36.51
        Pain in other parts, Week 24 (n=104, 28)
    -3.53 ± 35.35
    -4.76 ± 38.18
        Pain in other parts, Week 30 (n=81, 22)
    -2.88 ± 38.08
    -7.58 ± 20.40
        Pain in other parts, Week 36 (n=59, 15)
    -5.08 ± 33.23
    2.22 ± 29.46
        Pain in other parts, Week 42 (n=50, 13)
    -2.67 ± 33.56
    -12.82 ± 32.03
        Pain in other parts, Week 48 (n=43, 11)
    -4.65 ± 27.78
    -15.15 ± 34.52
        Pain in other parts, Week 57 (n=34, 7)
    -1.96 ± 34.76
    -9.52 ± 31.71
        Pain in other parts, Week 66 (n=29, 4)
    3.45 ± 37.10
    -16.67 ± 43.03
        Pain in other parts, Week 75 (n=24, 3)
    8.33 ± 31.47
    0.00 ± 0.00
        Pain in other parts, Week 84 (n=19, 2)
    -1.75 ± 39.24
    0.00 ± 0.00
        Pain in other parts, Week 93 (n=20, 1)
    -3.33 ± 28.41
    0.00 ± 99999
        Pain in other parts, Week 102 (n=16, 0)
    -4.17 ± 26.87
    00000 ± 00000
        Pain in other parts, Week 111 (n=13, 0)
    -5.13 ± 29.96
    00000 ± 00000
        Pain in other parts, Week 120 (n=14, 0)
    0.00 ± 26.15
    00000 ± 00000
        Pain in other parts, Week 129 (n=14, 0)
    -7.14 ± 14.19
    00000 ± 00000
        Pain in other parts, Week 138 (n=14, 0)
    -7.14 ± 19.30
    00000 ± 00000
        Pain in other parts, Week 147 (n=14, 0)
    0.00 ± 18.49
    00000 ± 00000
        Pain in other parts, Week 156 (n=7, 0)
    -14.29 ± 26.23
    00000 ± 00000
        Pain in other parts, Week 165 (n=8, 0)
    -16.67 ± 25.20
    00000 ± 00000
        Pain in other parts, Week 174 (n=7, 0)
    -9.52 ± 31.71
    00000 ± 00000
        Pain in other parts, Week 183 (n=4, 0)
    8.33 ± 63.10
    00000 ± 00000
        Pain in other parts, Week 192 (n=4, 0)
    -8.33 ± 31.91
    00000 ± 00000
        Pain in other parts, Week 201 (n=2, 0)
    -33.33 ± 0.00
    00000 ± 00000
        Pain in other parts, Week 210 (n=1, 0)
    -66.67 ± 99999
    00000 ± 00000
        Pain in other parts, SFUV (n=11, 13)
    9.09 ± 42.40
    0.00 ± 33.33
    No statistical analyses for this end point

    Secondary: Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score

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    End point title
    		 Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score
    End point description
    TTD with use of the EORTC is defined as the time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments or an initial = 10-point increase above baseline followed by either (a) death within 6 weeks from the last assessment through Week 48 or (b) death within 9 weeks from the last assessment from Week 48 thereafter. A = 10-point change in the EORTC scale score is perceived by participants as clinically significant (Osoba et al. 1998). '88888"=not estimable.
    End point type
    Secondary
    End point timeframe
    From baseline up to approximately 55 months
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    302
    151
    Units: Months
    median (confidence interval 95%)
        Dyspnoea
    88888 (19.0 to 88888)
    88888 (8.3 to 88888)
        Fatigue
    13.5 (8.3 to 88888)
    8.4 (5.6 to 88888)
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Time to deterioration for Fatigue (multi items QLQ-C30)
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.62
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.42
    Notes
    [1] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Time to deterioration for Dyspnoea (single item QLQ-C30)
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.975
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 1.78
    Notes
    [2] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.

    Secondary: Time to Deterioration in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score

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    End point title
    		 Time to Deterioration in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score
    End point description
    TTD with use of the EORTC is defined as the time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments or an initial = 10-point increase above baseline followed by either (a) death within 6 weeks from the last assessment through Week 48 or (b) death within 9 weeks from the last assessment from Week 48 thereafter. A = 10-point change in the EORTC scale score is perceived by participants as clinically significant. '88888"=not estimable.
    End point type
    Secondary
    End point timeframe
    From baseline up to approximately 55 months
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    302
    151
    Units: Months
    median (confidence interval 95%)
        Cough
    88888 (88888 to 88888)
    21.4 (13.9 to 88888)
        Chest Pain
    88888 (88888 to 88888)
    88888 (6.8 to 88888)
        Dyspnoea
    17.3 (9.6 to 34.2)
    8.3 (5.5 to 88888)
        Arm and/or Shoulder Pain
    21.3 (13.6 to 88888)
    13.9 (8.6 to 88888)
        Composite of Cough, Dyspnea and Chest Pain
    8.3 (5.5 to 17.3)
    4.2 (2.9 to 5.6)
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Time to deterioration for Cough (single item QLQ-LC13)
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 = 0.653
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 2.26
    Notes
    [3] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Time to Confirmed Deterioration for the Composite of the 3 following symptoms: cough, dyspnoea (multi-items QLQ-LC13) and chest pain
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [4]
    P-value
    		 = 0.041
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 0.99
    Notes
    [4] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Time to deterioration for Arm and/or shoulder pain (single item QLQ-LC13)
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 = 0.362
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 1.39
    Notes
    [5] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Time to deterioration for Chest pain (single item QLQ-LC13)
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 = 0.036
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.27
         upper limit
    		 0.97
    Notes
    [6] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.
    Statistical analysis title
    		 Statistical Analysis
    Statistical analysis description
    Time to deterioration for Dyspnoea (multiple items QLQ-LC13)
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [7]
    P-value
    		 = 0.125
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 1.11
    Notes
    [7] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.

    Secondary: Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status

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    End point title
    		 Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status
    End point description
    Investigator-assessed PFS according to RECIST v1.1 assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay.
    End point type
    Secondary
    End point timeframe
    From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    127
    78
    Units: Months
    median (confidence interval 95%)
        SP263 TC>=1%
    4.2 (2.9 to 5.8)
    3.0 (2.8 to 5.4)
    Statistical analysis title
    		 PFS SP263 TC>=1%
    Statistical analysis description
    SP263 TC>=1%
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [8]
    P-value
    		 = 0.366
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.64
         upper limit
    		 1.18
    Notes
    [8] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.

    Secondary: Overall Survival in Participants With PD-L1 Positive Status

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    End point title
    		 Overall Survival in Participants With PD-L1 Positive Status
    End point description
    Overall survival will be assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay.
    End point type
    Secondary
    End point timeframe
    From randomization up to death from any cause (up to approximately 55 months)
    End point values
    		 Atezolizumab Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects analysed
    127
    78
    Units: Months
    median (confidence interval 95%)
        SP263 TC>=1%
    9.4 (7.0 to 11.3)
    10.3 (7.1 to 12.3)
    Statistical analysis title
    		 OS SP263 TC>=1% Statistical Analysis
    Statistical analysis description
    SP263 TC>=1%
    Comparison groups
    Atezolizumab v Single Agent Chemotherapy (Vinorelbine or Gemcitabine)
    Number of subjects included in analysis
    205
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 = 0.272
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.61
         upper limit
    		 1.15
    Notes
    [9] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first study drug to the data cutoff date: 30 April 2022 (up to approximately 55 months)
    Adverse event reporting additional description
    For the 'Total # Deaths Resulting From Adverse Events' reported data, this is the number of deaths resulting from treatment related Adverse Events.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Chemotherapy
    Reporting group description
    		 Participants received single agent chemotherapy; either vinorelbine oral or IV, or gemcitabine IV, according to the label based on investigator’s choice.

    Reporting group title
    Atezolizumab
    Reporting group description
    		 Participants received atezolizumab 1200 milligrams (mg) intravenous (IV) infusion on Day 1 of each 21-day cycle until loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death.

    Serious adverse events
    		 Chemotherapy Atezolizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    53 / 147 (36.05%)
    146 / 300 (48.67%)
         number of deaths (all causes)
    129
    248
         number of deaths resulting from adverse events
    4
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Superior vena cava occlusion
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Capillary leak syndrome
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    2 / 147 (1.36%)
    7 / 300 (2.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
         deaths causally related to treatment / all
    0 / 2
    0 / 7
    Chest pain
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Infusion site extravasation
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Performance status decreased
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 147 (0.68%)
    3 / 300 (1.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Generalised oedema
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Systemic immune activation
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    2 / 147 (1.36%)
    9 / 300 (3.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Laryngeal haemorrhage
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated lung disease
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemoptysis
         subjects affected / exposed
    2 / 147 (1.36%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 147 (1.36%)
    6 / 300 (2.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 147 (1.36%)
    7 / 300 (2.33%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Asthma
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 147 (1.36%)
    8 / 300 (2.67%)
         occurrences causally related to treatment / all
    1 / 2
    8 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumothorax
         subjects affected / exposed
    0 / 147 (0.00%)
    3 / 300 (1.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary embolism
         subjects affected / exposed
    3 / 147 (2.04%)
    3 / 300 (1.00%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory failure
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disorientation
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Eastern Cooperative Oncology Group performance status worsened
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 147 (0.68%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radiation oesophagitis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute left ventricular failure
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Acute coronary syndrome
         subjects affected / exposed
    2 / 147 (1.36%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 147 (0.00%)
    3 / 300 (1.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 147 (0.68%)
    3 / 300 (1.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac disorder
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Sinus tachycardia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocarditis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myasthenia gravis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Lacunar stroke
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Generalised tonic-clonic seizure
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 147 (1.36%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myelosuppression
         subjects affected / exposed
    2 / 147 (1.36%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    3 / 147 (2.04%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 147 (0.68%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukocytosis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Ileus
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal toxicity
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal perforation
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune-mediated hepatitis
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 147 (1.36%)
    3 / 300 (1.00%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 147 (0.68%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Rheumatoid arthritis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture pain
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchitis
         subjects affected / exposed
    1 / 147 (0.68%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain abscess
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterocolitis bacterial
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    0 / 147 (0.00%)
    5 / 300 (1.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Influenza
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    4 / 147 (2.72%)
    5 / 300 (1.67%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Neutropenic sepsis
         subjects affected / exposed
    2 / 147 (1.36%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    11 / 147 (7.48%)
    33 / 300 (11.00%)
         occurrences causally related to treatment / all
    6 / 13
    3 / 37
         deaths causally related to treatment / all
    1 / 2
    0 / 8
    Pneumonia aspiration
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia bacterial
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Relapsing fever
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    4 / 147 (2.72%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    2 / 4
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 147 (0.68%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 147 (0.00%)
    3 / 300 (1.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 147 (0.00%)
    3 / 300 (1.00%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    0 / 147 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 147 (0.00%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Chemotherapy Atezolizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    128 / 147 (87.07%)
    234 / 300 (78.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    7 / 147 (4.76%)
    21 / 300 (7.00%)
         occurrences all number
    9
    31
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    19 / 147 (12.93%)
    43 / 300 (14.33%)
         occurrences all number
    25
    49
    Fatigue
         subjects affected / exposed
    34 / 147 (23.13%)
    57 / 300 (19.00%)
         occurrences all number
    34
    73
    Oedema peripheral
         subjects affected / exposed
    6 / 147 (4.08%)
    25 / 300 (8.33%)
         occurrences all number
    6
    28
    Pyrexia
         subjects affected / exposed
    9 / 147 (6.12%)
    30 / 300 (10.00%)
         occurrences all number
    17
    35
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis
         subjects affected / exposed
    9 / 147 (6.12%)
    19 / 300 (6.33%)
         occurrences all number
    10
    26
    Dyspnoea
         subjects affected / exposed
    14 / 147 (9.52%)
    55 / 300 (18.33%)
         occurrences all number
    15
    59
    Cough
         subjects affected / exposed
    13 / 147 (8.84%)
    59 / 300 (19.67%)
         occurrences all number
    14
    72
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    5 / 147 (3.40%)
    17 / 300 (5.67%)
         occurrences all number
    5
    18
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    4 / 147 (2.72%)
    15 / 300 (5.00%)
         occurrences all number
    5
    25
    Neutrophil count decreased
         subjects affected / exposed
    17 / 147 (11.56%)
    1 / 300 (0.33%)
         occurrences all number
    25
    1
    Weight decreased
         subjects affected / exposed
    11 / 147 (7.48%)
    22 / 300 (7.33%)
         occurrences all number
    12
    29
    White blood cell count decreased
         subjects affected / exposed
    14 / 147 (9.52%)
    2 / 300 (0.67%)
         occurrences all number
    24
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    8 / 147 (5.44%)
    14 / 300 (4.67%)
         occurrences all number
    10
    18
    Headache
         subjects affected / exposed
    7 / 147 (4.76%)
    15 / 300 (5.00%)
         occurrences all number
    7
    20
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    11 / 147 (7.48%)
    4 / 300 (1.33%)
         occurrences all number
    15
    4
    Anaemia
         subjects affected / exposed
    48 / 147 (32.65%)
    48 / 300 (16.00%)
         occurrences all number
    70
    55
    Neutropenia
         subjects affected / exposed
    18 / 147 (12.24%)
    2 / 300 (0.67%)
         occurrences all number
    39
    3
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    29 / 147 (19.73%)
    47 / 300 (15.67%)
         occurrences all number
    32
    60
    Diarrhoea
         subjects affected / exposed
    24 / 147 (16.33%)
    40 / 300 (13.33%)
         occurrences all number
    45
    57
    Nausea
         subjects affected / exposed
    35 / 147 (23.81%)
    32 / 300 (10.67%)
         occurrences all number
    53
    40
    Vomiting
         subjects affected / exposed
    22 / 147 (14.97%)
    25 / 300 (8.33%)
         occurrences all number
    41
    33
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    3 / 147 (2.04%)
    23 / 300 (7.67%)
         occurrences all number
    3
    34
    Rash
         subjects affected / exposed
    5 / 147 (3.40%)
    30 / 300 (10.00%)
         occurrences all number
    7
    45
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    0 / 147 (0.00%)
    19 / 300 (6.33%)
         occurrences all number
    0
    22
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    12 / 147 (8.16%)
    27 / 300 (9.00%)
         occurrences all number
    15
    35
    Back pain
         subjects affected / exposed
    13 / 147 (8.84%)
    25 / 300 (8.33%)
         occurrences all number
    14
    29
    Pain in extremity
         subjects affected / exposed
    8 / 147 (5.44%)
    12 / 300 (4.00%)
         occurrences all number
    9
    12
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    5 / 147 (3.40%)
    15 / 300 (5.00%)
         occurrences all number
    5
    16
    Urinary tract infection
         subjects affected / exposed
    12 / 147 (8.16%)
    29 / 300 (9.67%)
         occurrences all number
    15
    46
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    32 / 147 (21.77%)
    66 / 300 (22.00%)
         occurrences all number
    39
    74
    Hypokalaemia
         subjects affected / exposed
    2 / 147 (1.36%)
    17 / 300 (5.67%)
         occurrences all number
    2
    26
    Hyponatraemia
         subjects affected / exposed
    7 / 147 (4.76%)
    25 / 300 (8.33%)
         occurrences all number
    7
    28

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Jan 2018
    The protocol has been amended to include clarification of the key inclusion criteria in order to avoid the inclusion of too young participants with comorbidities or contraindications. The text on comparator chemotherapy administration guidelines has been amended to include both, administration per relevant local guidelines and per Summary of Product Characteristics (SmPC) management as these may differ. The exclusion of participants with uncontrolled hypercalcaemia, including the exclusion of participants taking denosumab has been amended.
    19 Dec 2019
    The protocol has been amended with the addition of an efficacy interim analysis with adequate power for the primary endpoint. OS and investigator-assessed PFS according to RECIST v1.1 in participants with PD-L1 expression defined by the SP263 immunohistochemistry (IHC) assay has been added as a secondary analysis. The list of atezolizumab risks has been updated to include myositis.
    03 Feb 2021
    The protocol has been amended to include severe cutaneous adverse reactions to the list of identified risks for atezolizumab. Text has been added to clarify that hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are considered potential risks for atezolizumab. List of identified risks for vinorelbine have been revised due to revisions of the Summary of Product Characteristics.
    22 Dec 2021
    The protocol has been amended to include a time limit for the final analysis as an alternative to the target 380 overall survival (OS) events. The adverse event management guidelines have been updated to align with the Atezolizumab Investigator’s Brochure, Version 18.

    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
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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