Flag of the European Union

EU Clinical Trials Register

Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:

interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC

clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

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

The EU Clinical Trials Register currently displays 44339 clinical trials with a EudraCT protocol, of which 7369 are clinical trials conducted with subjects less than 18 years old. The register also displays information on 18700 older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).

Examples: Cancer AND drug name. Pneumonia AND sponsor name.
How to search [pdf]

Advanced Search:

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

< Back to search results

Clinical Trial Results:
A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naive Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy (IPSOS)

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	25 Oct 2023

Results information
Results version number	v2(current)
This version publication date	16 Oct 2024
First version publication date	05 May 2023
Other versions	v1
Version creation reason

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

MO29872

ISRCTN number

-

US NCT number

NCT03191786

WHO universal trial number (UTN)

-

Sponsor organisation name

F. Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4058

Public contact

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

Scientific contact

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

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

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

Analysis stage

Final

Date of interim/final analysis

25 Oct 2023

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

25 Oct 2023

Was the trial ended prematurely?

No

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

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 7

Country: Number of subjects enrolled

Belgium: 8

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

Country: Number of subjects enrolled

Luxembourg: 1

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

Top of page

Recruitment details

Participants diagnosed with advanced or recurrent (stage IIIb) or metastatic (stage IV) NSCLC took part in the study across 85 investigative sites in 23 countries from 11 Sep 2017 to 25 Oct 2023.

Screening details

A total of 453 participants were randomized in 2:1 ratio to atezolizumab arm and single agent chemotherapy arm in this study. Of these 453, 447 participants received at least 1 dose of study treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Atezolizumab

Arm description

Participants received atezolizumab 1200 milligrams (mg), as 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 mg, 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.

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 until disease progression unacceptable toxicity, participant or physician decision to discontinue, or death.

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
Safety evaluable population	300	147
Completed	0	0
Not completed	302	151
Adverse event, serious fatal	236	127
Physician decision	1	-
Consent withdrawn by subject	26	16
Lost to follow-up	9	3
Moved to Post Trial Access Program	30	5

Baseline characteristics

Top of page

Reporting group title

Atezolizumab

Reporting group description

Participants received atezolizumab 1200 milligrams (mg), as 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 until disease progression unacceptable toxicity, participant or physician decision to discontinue, or death.

Reporting group values	Atezolizumab	Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	Total
Number of subjects	302	151	453
Age categorical
Units: participants
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	22	69
Not Hispanic or Latino	242	126	368
Unknown or Not Reported	13	3	16

End points

Top of page

Reporting group title

Atezolizumab

Reporting group description

Participants received atezolizumab 1200 milligrams (mg), as 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 until disease progression unacceptable toxicity, participant or physician decision to discontinue, or death.

Primary: Overall Survival (OS)

Top of page

End point title

Overall Survival (OS)

End point description

OS was defined as the time between the date of randomization and the date of death due to any cause. Kaplan-Meier (KM) estimates were used to calculate median. Intent-to-Treat (ITT) population included all randomized participants irrespective of whether the assigned treatment was actually received.

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)

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

= 0.025

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

Top of page

End point title

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

End point description

OS was defined as the time between the date of randomization and the date of death due to any cause. OS rate at 6, 12, 18 and 24 months were estimated for each treatment arm using KM methodology. Percentages were rounded off to the nearest decimal point. ITT population included all randomized participants irrespective of whether the assigned treatment was actually received.

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 of participants
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)

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

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

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

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, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)

Top of page

End point title

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

End point description

Objective response rate (ORR)=best overall response(BOR) of either complete response(CR)/partial response(PR), as determined by investigator with use of RECIST v1.1. CR=disappearance of all target lesions/any pathological lymph nodes (target/non-target) having a reduction in short axis to <10 millimeters (mm). PR=at least 30% decrease in sum of diameters(SOD) of target lesions, taking as reference the baseline SOD. A minimum interval of 6 weeks (42 days) was considered for stable disease (SD) to be assigned as BOR, i.e. in case the single response is SD, PR/CR, this single response must be assessed no less than 6 weeks (42 days) after start date of study treatment. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD while in the study. Percentages were rounded off to the nearest decimal point. ITT population=randomized participants irrespective of whether the assigned treatment was actually received.

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

Top of page

End point title

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

End point description

PFS was 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. Progressive disease (PD) was defined as at least 20% increase in the sum of diameters of lesions, taking as reference the smallest sum during the study (nadir), including baseline. KM estimates were used to calculate median. ITT population included all randomized participants irrespective of whether the assigned treatment was actually received.

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)

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: Percentage of Participants With At Least One Adverse Events (AE)

Top of page

End point title

Percentage of Participants With At Least One Adverse Events (AE)

End point description

An AE was any untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product. AEs were reported based on the National Cancer Institute Common Terminology Criteria for AEs, version 4.0 (NCI-CTCAE, v4.0). Safety-evaluable population included all randomized participants who received any amount of study treatment.

End point type

Secondary

End point timeframe

Baseline up to 90 days after last dose of atezolizumab (approximately 62 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: Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1

Top of page

End point title

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

End point description

DOR= 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 participants who have a best overall response as CR or PR. CR=disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD=at least 20% increase in the sum of diameters of lesions, taking as reference the smallest sum during the study (nadir), including baseline. KM estimates were used to calculate median. ITT population=all randomized participants irrespective of whether the assigned treatment was actually received. Number analyzed is the number of participants with objective response (i.e. responders).

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

Top of page

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=30 questions that assess 5 aspects of patient functioning, 3 symptom scales, global health/quality of life, and 6 single items. All EORTC scales & single-item measures are linearly transformed so that each score has range of 0-100. A high score for functional/global health status scale represents high/healthy level of functioning/HRQoL (Health-Related Quality of Life); however high score for symptom scale/ item represents high level of symptomatology/problems. A ≥10-point change in symptoms subscale score was perceived as clinically significant. A positive change from baseline=improvement & negative change from baseline indicated worsening.'99999'=standard deviation (SD) non-estimable due to 1 participant evaluated.'00000'=data not reported due to no participant evaluated. ITT population=all randomized participants irrespective of whether the assigned treatment was actually received."n”=number of participants with data available for analysis at the specified timepoint.

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

Top of page

End point title

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

End point description

EORTC QLQ-LC13 module incorporates 1 multiple item scale to assess dyspnea &series of single items assessing pain,coughing,sore mouth,dysphagia, peripheral neuropathy,alopecia,& hemoptysis. It was scored according to EORTC scoring manual. All EORTC scales & single-item measures are linearly transformed so that each score has a range of 0-100. A high score for functional/global health status scale =high/healthy level of functioning/HRQoL (Health-Related Quality of Life); high score for symptom scale/item = high level of symptomatology/problems. A≥10-point change in the symptoms subscale score was perceived as clinically significant. '99999'=standard deviation (SD) non-estimable due to 1 participant evaluated. '00000'=data not reported due to no participant evaluated. ITT Population=all randomized participants irrespective of whether the assigned treatment was actually received. "n"=number of participants with data available for analysis at the specified timepoint.

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

Top of page

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 was 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 was 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 was perceived by participants as clinically significant (Osoba et al. 1998). '88888"=not estimable. ITT population included all randomized participants irrespective of whether the assigned treatment was actually received.

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

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

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: TTD in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score

Top of page

End point title

TTD in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score

End point description

TTD with use of the EORTC = time from randomization to the first confirmed clinically meaningful deterioration in EORTC symptom scores. Confirmed clinically meaningful deterioration in lung cancer symptoms was = 10-point increase above baseline in a symptom score that must be held for at least two consecutive assessments/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 was perceived by participants as clinically significant. '88888"=not estimable. ITT population included all randomized participants irrespective of whether the assigned treatment was actually received.

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

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

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 ^[4]

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
[4] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.

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 ^[5]

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
[5] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.

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 ^[6]

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
[6] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.

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 ^[7]

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
[7] - Stratified analysis. Histologic subtype, PD-L1 IHC status and brain metastases (Yes/No) were added as stratification factors.

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

Top of page

End point title

PFS, as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status

End point description

PFS was 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. PD was defined as at least 20% increase in the sum of diameters of lesions, taking as reference the smallest sum during the study (nadir), including baseline. Investigator-assessed PFS was assessed in participants whose tumors express PD-L1 protein as measured by PD-L1 SP263 IHC assay. KM estimates were used to calculate the median. ITT Population included all randomized participants irrespective of whether the assigned treatment was actually received. Number analyzed is the number of participants with data available for analysis.

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)

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: OS in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Status

Top of page

End point title

OS in Participants With Programmed Death-Ligand 1 (PD-L1) Positive Status

End point description

OS was defined as the time between the date of randomization and the date of death due to any cause. OS was assessed in participants whose tumors express PD-L1 protein (i.e., tumor cell (TC) ≥1%) as measured by PD-L1 SP263 immunohistochemistry (IHC) assay. KM estimates were used to calculate the median. ITT Population included all randomized participants irrespective of whether the assigned treatment was actually received. Number analyzed is the number of participants with data available for analysis.

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)

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

Top of page

Timeframe for reporting adverse events

From Day 1 up to 90 days after last atezolizumab dose (up to approximately 62 months)

Adverse event reporting additional description

Safety population included participants who received any amount of any study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.1

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 until disease progression unacceptable toxicity, participant or physician decision to discontinue, or death.

Reporting group title

Atezolizumab

Reporting group description

Participants received atezolizumab 1200 mg, as 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	Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	Atezolizumab
Total subjects affected by serious adverse events
subjects affected / exposed	54 / 147 (36.73%)	147 / 300 (49.00%)
number of deaths (all causes)	129	248
number of deaths resulting from adverse events	13	35
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
Iliac artery dissection
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
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
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
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
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
General disorders and administration site conditions
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
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
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
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
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
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
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
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
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
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
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
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
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%)	2 / 300 (0.67%)
occurrences causally related to treatment / all	0 / 1	1 / 2
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
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
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
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
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
Cardiac disorders
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 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
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 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
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
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
Nervous system disorders
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
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
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
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
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
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
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
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
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
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
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
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
Gastrointestinal disorders
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	1 / 1
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
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
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
Constipation
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
Abdominal pain upper
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
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
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
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
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
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
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
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
Musculoskeletal and connective tissue disorders
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
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
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
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
Periarthritis
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
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
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
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
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
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
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
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
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
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
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
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%)	34 / 300 (11.33%)
occurrences causally related to treatment / all	6 / 13	4 / 38
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	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
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
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
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
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
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
Klebsiella urinary tract infection
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
Gastroenteritis salmonella
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
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
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
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
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
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
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
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
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

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

Non-serious adverse events	Single Agent Chemotherapy (Vinorelbine or Gemcitabine)	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	6 / 147 (4.08%)	23 / 300 (7.67%)
occurrences all number	8	39
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%)	58 / 300 (19.33%)
occurrences all number	34	74
Oedema peripheral
subjects affected / exposed	6 / 147 (4.08%)	25 / 300 (8.33%)
occurrences all number	6	28
Pyrexia
subjects affected / exposed	10 / 147 (6.80%)	30 / 300 (10.00%)
occurrences all number	18	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%)	56 / 300 (18.67%)
occurrences all number	15	60
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	26
Neutrophil count decreased
subjects affected / exposed	17 / 147 (11.56%)	2 / 300 (0.67%)
occurrences all number	26	2
Weight decreased
subjects affected / exposed	11 / 147 (7.48%)	22 / 300 (7.33%)
occurrences all number	13	30
White blood cell count decreased
subjects affected / exposed	15 / 147 (10.20%)	2 / 300 (0.67%)
occurrences all number	26	2
Nervous system disorders
Headache
subjects affected / exposed	7 / 147 (4.76%)	15 / 300 (5.00%)
occurrences all number	7	20
Dizziness
subjects affected / exposed	8 / 147 (5.44%)	14 / 300 (4.67%)
occurrences all number	10	18
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	48 / 147 (32.65%)	50 / 300 (16.67%)
occurrences all number	70	57
Leukopenia
subjects affected / exposed	11 / 147 (7.48%)	3 / 300 (1.00%)
occurrences all number	15	3
Neutropenia
subjects affected / exposed	18 / 147 (12.24%)	2 / 300 (0.67%)
occurrences all number	39	3
Gastrointestinal disorders
Constipation
subjects affected / exposed	28 / 147 (19.05%)	48 / 300 (16.00%)
occurrences all number	31	61
Diarrhoea
subjects affected / exposed	24 / 147 (16.33%)	40 / 300 (13.33%)
occurrences all number	45	57
Nausea
subjects affected / exposed	36 / 147 (24.49%)	32 / 300 (10.67%)
occurrences all number	54	40
Vomiting
subjects affected / exposed	23 / 147 (15.65%)	25 / 300 (8.33%)
occurrences all number	42	33
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	5 / 147 (3.40%)	30 / 300 (10.00%)
occurrences all number	7	44
Pruritus
subjects affected / exposed	3 / 147 (2.04%)	23 / 300 (7.67%)
occurrences all number	3	34
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 147 (0.00%)	19 / 300 (6.33%)
occurrences all number	0	22
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	8 / 147 (5.44%)	12 / 300 (4.00%)
occurrences all number	9	12
Back pain
subjects affected / exposed	13 / 147 (8.84%)	25 / 300 (8.33%)
occurrences all number	14	29
Arthralgia
subjects affected / exposed	12 / 147 (8.16%)	28 / 300 (9.33%)
occurrences all number	15	36
Infections and infestations
Pneumonia
subjects affected / exposed	5 / 147 (3.40%)	15 / 300 (5.00%)
occurrences all number	6	15
Urinary tract infection
subjects affected / exposed	12 / 147 (8.16%)	29 / 300 (9.67%)
occurrences all number	15	47
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	32 / 147 (21.77%)	66 / 300 (22.00%)
occurrences all number	40	75
Hypokalaemia
subjects affected / exposed	2 / 147 (1.36%)	18 / 300 (6.00%)
occurrences all number	2	28
Hyponatraemia
subjects affected / exposed	7 / 147 (4.76%)	25 / 300 (8.33%)
occurrences all number	7	28

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

29 Jun 2017

This protocol was amended to 1. Exclude participants younger than 70 years with ECOG PS 0/1 in line with ESMO guidelines. 2. Include participants deemed ‘unsuitable for any platinum doublet chemotherapy’ as opposed to ‘unsuitable for platinum containing therapy’ to appropriately recruit cisplatin and carboplatin ineligible participants. 3. Increased frequency of on-treatment pregnancy tests and regular post-discontinuation visit pregnancy testing until at least 5 months after the last dose of atezolizumab or until at least 6 months after the last dose of chemotherapy.

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 SmPC management as these may differ. The exclusion of participants with uncontrolled hypercalcaemia, including the exclusion of participants taking denosumab has been amended.

14 Jan 2019

The protocol has been amended to include the requirement for female participants of childbearing potential randomized to the atezolizumab arm to refrain from donating eggs to inclusion criteria.

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 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.

09 May 2023

This protocol is amended to: 1. Include myelitis and facial paresis in list of identified risks. 2. Hemophagocytic lymphohistiocytosis (HLH) has been updated from a potential risk to an identified risk associated with atezolizumab.

Were there any global interruptions to the trial? No

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

None reported

For support, Contact us.

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

European Medicines Agency © 1995-Fri May 30 09:35:23 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands