Trial Outcomes & Findings for An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene (NCT NCT00932451)

Last Updated: 2017-01-13

Results Overview

The objective response rate (ORR) as a measure of anti-tumor efficacy of oral PF-02341066 in participants with advanced NSCLC with an ALK gene translocation or inversion after failure of at least one line of chemotherapy.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

1069 participants

Primary outcome timeframe

6 years

Results posted on

2017-01-13

Participant Flow

A total of 1069 participants entered the study out of which 3 participants were withdrawn from the study before receiving study treatment because they were not eligible and were mistakenly entered into the interactive voice response system. Only 1066 participants received greater than or equal to 1 dose of crizotinib.

A total of 144 participants in study NCT00932893 were also enrolled in this study to receive treatment with crizotinib, including 143 participants randomized to the chemotherapy arm then crossed over in this study and 1 participant initially erroneously randomized in the crizotinib arm but not treated.

Participant milestones

Participant milestones
Measure	Crizotinib 250 mg BID Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.
Overall Study STARTED	1066
Overall Study COMPLETED	244
Overall Study NOT COMPLETED	822

Reasons for withdrawal

Reasons for withdrawal
Measure	Crizotinib 250 mg BID Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.
Overall Study Withdrawal by Subject	69
Overall Study Lost to Follow-up	22
Overall Study Death	726
Overall Study Other reasons	5

Baseline Characteristics

An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.
Age, Continuous	52.2 Years STANDARD_DEVIATION 12.33 • n=5 Participants
Age, Customized < 65 years	894 Participants n=5 Participants
Age, Customized >=65 years	172 Participants n=5 Participants
Gender Female	601 Participants n=5 Participants
Gender Male	465 Participants n=5 Participants
Race/Ethnicity, Customized Chinese	252 participants n=5 Participants
Race/Ethnicity, Customized Japanese	81 participants n=5 Participants
Race/Ethnicity, Customized Korean	144 participants n=5 Participants
Race/Ethnicity, Customized White	532 participants n=5 Participants
Race/Ethnicity, Customized Black	20 participants n=5 Participants
Race/Ethnicity, Customized Other	19 participants n=5 Participants
Race/Ethnicity, Customized Other-Asian	18 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 years

Population: Response-evaluable populations: defined as participants in either the SA-ALK positive by IUO population or SA-ALK positive by non-IUO population, respectively, who had adequate baseline tumor assessment.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Objective Response Rate ALK Positive by IUO; N=908	54.1 Percentage of participants Interval 50.8 to 57.4	—
Objective Response Rate ALK Positive by non-IUO only, N= 158	40.5 Percentage of participants Interval 32.8 to 48.6	—

PRIMARY outcome

Timeframe: 6 years

Population: The safety analysis population included all participants who were enrolled and received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing).

Incidence of adverse events and laboratory abnormalities (severity graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], version 4.0).

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Percentage of Participants With Adverse Events Serious AEs (all causalities)	50.6 Percentage of Participants	—
Percentage of Participants With Adverse Events Grade 3/4 AEs (all causalities)	65.6 Percentage of Participants	—
Percentage of Participants With Adverse Events Grade 5 AEs (all causalities)	22.7 Percentage of Participants	—
Percentage of Participants With Adverse Events Serious AEs (treatment related)	11.5 Percentage of Participants	—
Percentage of Participants With Adverse Events Grade 3/4 AEs (treatment related)	40.2 Percentage of Participants	—
Percentage of Participants With Adverse Events Grade 5 AEs (treatment related)	1.6 Percentage of Participants	—

SECONDARY outcome

Timeframe: 6 years

DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to the first documentation of objective tumor progression or to death on study due to any cause, whichever occurred first. DR (in months) was calculated as (first date of PD or death - first date of CR or PR that was subsequently confirmed + 1)/30.4.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Duration of Response (DR) ALK Positive by IUO, N=491	11.8 Months Interval 10.4 to 12.8	—
Duration of Response (DR) ALK Positive by non-IUO only, N=64	9.5 Months Interval 6.9 to 15.2	—

SECONDARY outcome

Timeframe: 6 years

TTR was defined as the time (in weeks) from the date of Cycle 1 Day 1 dose to first documentation of objective tumor response (CR or PR) that was subsequently confirmed. For participants proceeding from PR to CR, the onset of PR was taken as the onset of response.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Time to Tumor Response (TTR) ALK Positive by IUO (n=491)	6.1 Weeks Interval 2.7 to 164.0	—
Time to Tumor Response (TTR) ALK Positive by non-IUO only (n=64)	6.3 Weeks Interval 4.7 to 65.9	—

SECONDARY outcome

Timeframe: 6 years

DCR at 6 and 12 weeks was defined as the percentage of participants with a confirmed CR, confirmed PR, or SD (according to RECIST v 1.1) at 6 weeks and 12 weeks, respectively.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Disease Control Rate (DCR) ALK Positive by IUO at Week 6, N=908	81.7 Percentage of participants Interval 79.0 to 84.2	—
Disease Control Rate (DCR) ALK Positive by IUO at Week 12, N=908	70.8 Percentage of participants Interval 67.7 to 73.8	—
Disease Control Rate (DCR) ALK Positive by non-IUO at Week 6, N=158	69.6 Percentage of participants Interval 61.8 to 76.7	—
Disease Control Rate (DCR) ALK Positive by non-IUO at Week 12, N=158	61.4 Percentage of participants Interval 53.3 to 69.0	—

SECONDARY outcome

Timeframe: 6 years

Population: The safety analysis populations included all participants who received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing), and were ALK positive either by IUO (SA-ALK positive by IUO population) or by non-IUO (SA-ALK positive by non-IUO population), respectively.

PFS was defined as the time from the date of the Cycle 1 Day 1 dose to the date of the first documentation of objective tumor progression or death on study due to any cause, whichever occurred first.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Progression Free Survival (PFS) ALK Positive by IUO , N= 908	8.4 Months Interval 7.1 to 9.7	—
Progression Free Survival (PFS) ALK Positive by non-IUO only , N=158	6.9 Months Interval 5.6 to 9.4	—

SECONDARY outcome

Timeframe: 6 years

OS was defined as the time from the Cycle 1 Day 1 dose to the date of death due to any cause. OS (in months) was calculated as (date of death - date of Cycle 1 Day 1 dose + 1)/30.4.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Overall Survival (OS) ALK-positive by IUO (N= 908)	21.8 Months Interval 19.4 to 24.0	—
Overall Survival (OS) ALK-positive by non-IUO (N= 158)	16.9 Months Interval 13.4 to 21.5	—

SECONDARY outcome

Timeframe: 6 years

Six-month and 1-year survival probabilities were defined as the probabilities of survival at 6 months and 1 year, respectively, after the date of the Cycle 1 Day 1 dose based on the Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Probability of Survival ALK positive by non IUO at 6 Months	77.5 Percentage of probability Interval 70.1 to 83.3	—
Probability of Survival ALK positive by IUO at 12 Months	66.5 Percentage of probability Interval 63.3 to 69.5	—
Probability of Survival ALK positive by non IUO at 12 Months	62.4 Percentage of probability Interval 54.3 to 69.6	—
Probability of Survival ALK positive by IUO at 6 Months	81.7 Percentage of probability Interval 79.0 to 84.0	—

SECONDARY outcome

Timeframe: 6 years

Population: All participants who have ≥ 1 measurement of PF-02341066 or PF-06260182 at the time of reporting are included in PK analysis. Concentration at Cycle 2 Day 1 and beyond are considered steady state, and only included those who received at least 14 continuous days of 250 mg BID dosing.

Plasma concentrations of crizotinib (PF-02341066) and its metabolite PF-06260182. The method of dispersion is % coefficient of variation.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=906 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 n=904 Participants PF-06260182 was a PF-02341066 metabolite measured in this study.
Plasma Concentrations of Crizotinib (PF-02341066) and Its Metabolite PF-06260182 Cycle 1 Day 1 (N= 13, 13)	1.95 ng/mL Geometric Coefficient of Variation 55	0.00601 ng/mL Geometric Coefficient of Variation 167
Plasma Concentrations of Crizotinib (PF-02341066) and Its Metabolite PF-06260182 Cycle 2 Day 1 (N=447, 431)	279 ng/mL Geometric Coefficient of Variation 46	76.2 ng/mL Geometric Coefficient of Variation 79
Plasma Concentrations of Crizotinib (PF-02341066) and Its Metabolite PF-06260182 Cycle 3 Day 1 (N=398, 385)	297 ng/mL Geometric Coefficient of Variation 44	80.8 ng/mL Geometric Coefficient of Variation 58
Plasma Concentrations of Crizotinib (PF-02341066) and Its Metabolite PF-06260182 Cycle 5 Day 1 (N=297, 290)	294 ng/mL Geometric Coefficient of Variation 48	81.4 ng/mL Geometric Coefficient of Variation 61

SECONDARY outcome

Timeframe: 6 years

Population: The safety analysis population included all participants who received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing) and were ALK positive by IUO (SA-ALK positive by IUO population)

Molecular profiling outcomes included:Types of EML4-ALK fusion variants and ALK protein expression; Although a secondary objective was defined to explore the relationship of ALK gene fusion to the presence of ALK protein and fusion transcript, no additional analyses of ALK fusion variants or ALK protein were performed for technical reasons. Analyses of change from Baseline in the expression of biomarkers relevant to signaling pathways were not performed because paired Baseline and on-treatment (Cycle 2) tumor tissue required for the analysis, which were to be collected on an optional basis, were not available.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=908 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Molecular Profiling (ALK Status) Descriptive Statistics for ALK Percentage of Positive Cells by Central Laboratory Test (SA [ALK Positive by IUO] Population)	60.0 Percentage of cells Full Range 21.18 • Interval 15.0 to 100.0	—

SECONDARY outcome

Timeframe: 6 years

Population: The All Genotyped Population was defined as all participants in the safety analysis population who had at least 1 genotype result. The Pharmacogenomic Evaluable (PE) Population was defined as participants in the All Genotyped Population who had an HLA genotype result and were designated as an ALT Case or Control.

The frequency of the candidate gene alleles, HLA-DQA1\*02:01, HLA-DQB1\*02:02, HLA-DRB1\*07:01 and TNXB/rs12153855, were measured in alanine transaminase (ALT) Cases and ALT Controls to evaluate if there were statistically significant associations that would support or suggest any predictive (ie, diagnostic) value of these markers in identifying participants who were at increased risk for hepatic toxicity. The frequency of 2 additional HLA gene alleles, HLA-B\*57:01 and HLA-DRB1\*15:01, were also measured in ALT Cases and ALT Controls. ALT Cases are defined as those patients with a baseline ALT of ≤1xULN and at least one on-treatment ALT assessment of \>3x upper limit of normal (ULN), and ALT Controls represent those patients with baseline and on-treatment assessments of ALT of ≤1xULN.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=74 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 n=115 Participants PF-06260182 was a PF-02341066 metabolite measured in this study.
Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population) HLA-DQA1*02:01	20.3 Percentage of participants	20.0 Percentage of participants
Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population) HLA-DQB1*02:02	17.6 Percentage of participants	16.5 Percentage of participants
Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population) HLA-DRB1*07:01	20.3 Percentage of participants	20.0 Percentage of participants
Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population) TNXB/rs12153855	10.8 Percentage of participants	16.5 Percentage of participants
Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population) HLA-B*57:01	2.7 Percentage of participants	4.3 Percentage of participants
Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population) HLA-DRB1*15:01	17.6 Percentage of participants	20.9 Percentage of participants

SECONDARY outcome

Timeframe: 6 years

Population: Participants from the SA population who had a Baseline (last ECG \[electrocardiogram\] prior to Cycle 1 Day 1 dose) and ≥1 post Baseline ECG measurement and were not included in the ECG sub-study.

The percentage of participants with maximum post-dose QTcF/QTcB (\<450, 450 - \<480, 480 - \<500, and ≥500 msec) were evaluated.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=999 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
QTc Prolongation in Participants Maximum QTcF Interval (<450)	89.8 Percentage of participants	—
QTc Prolongation in Participants Maximum QTcF Interval (450-<480)	7.7 Percentage of participants	—
QTc Prolongation in Participants Maximum QTcF Interval (480 - <500)	1.0 Percentage of participants	—
QTc Prolongation in Participants Maximum QTcF Interval (≥500)	1.5 Percentage of participants	—
QTc Prolongation in Participants Maximum QTcB Interval (<450)	74.3 Percentage of participants	—
QTc Prolongation in Participants Maximum QTcB Interval (450-<480)	21.2 Percentage of participants	—
QTc Prolongation in Participants Maximum QTcB Interval (480-<500)	2.4 Percentage of participants	—
QTc Prolongation in Participants Maximum QTcB Interval (≥500)	2.1 Percentage of participants	—

SECONDARY outcome

Timeframe: 6 years

Population: The patient reported outcomes (PRO) evaluable population was defined as the participants from the safety analysis (SA) population who completed a baseline assessment and at least one post-baseline assessment.

The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), global health status/quality of life, disease/treatment related symptoms (fatigue, pain, nausea/vomiting, dyspnea, appetite loss, sleep disturbance, constipation, and diarrhoea), and the perceived financial impact of disease. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-C30 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher ("worse") symptom severity, higher ("better") functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=976 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE5/DAY1 (n=806)	11.5 Units on a scale Standard Deviation 23.9	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE8/DAY1 (n=699)	12.3 Units on a scale Standard Deviation 24.1	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE9/DAY1 (n=665)	11.8 Units on a scale Standard Deviation 23.5	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE10/DAY1 (n=631)	11.5 Units on a scale Standard Deviation 23.6	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE11/DAY1 (n=570)	10.4 Units on a scale Standard Deviation 23.9	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE12/DAY1 (n=411)	10.1 Units on a scale Standard Deviation 21.6	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE13/DAY1 (n=512)	11.0 Units on a scale Standard Deviation 24.0	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE14/DAY1 (n=353)	10.4 Units on a scale Standard Deviation 21.5	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. End of treatment (n=450)	-1.0 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE2/DAY1 (n=929)	7.9 Units on a scale Standard Deviation 22.2	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE3/DAY1 (n=872)	10.6 Units on a scale Standard Deviation 23.7	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE4/DAY1 (n=828)	12.2 Units on a scale Standard Deviation 24.9	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE6/DAY1 (n=774)	11.9 Units on a scale Standard Deviation 24.8	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE7/DAY1 (n=734)	12.3 Units on a scale Standard Deviation 24.7	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE15/DAY1 (n=462)	9.5 Units on a scale Standard Deviation 23.9	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE16/DAY1 (n=294)	7.4 Units on a scale Standard Deviation 23.2	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE17/DAY1 (n=419)	8.0 Units on a scale Standard Deviation 24.3	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE18/DAY1 (n=247)	7.8 Units on a scale Standard Deviation 22.0	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE19/DAY1 (n=376)	7.8 Units on a scale Standard Deviation 23.1	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE20/DAY1 (n=222)	9.1 Units on a scale Standard Deviation 22.4	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE21/DAY1 (n=340)	7.8 Units on a scale Standard Deviation 22.5	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE22/DAY1 (n=179)	5.9 Units on a scale Standard Deviation 23.7	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE23/DAY1 (n=305)	6.7 Units on a scale Standard Deviation 24.0	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE24/DAY1 (n=154)	6.4 Units on a scale Standard Deviation 25.0	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE25/DAY1 (n=293)	4.7 Units on a scale Standard Deviation 23.3	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE26/DAY1 (n=127)	8.3 Units on a scale Standard Deviation 24.7	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE27/DAY1 (n=269)	5.9 Units on a scale Standard Deviation 23.2	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE28/DAY1 (n=120)	6.7 Units on a scale Standard Deviation 24.2	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE29/DAY1 (n=247)	5.7 Units on a scale Standard Deviation 23.3	—
Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores. CYCLE30/DAY1 (n=105)	6.4 Units on a scale Standard Deviation 24.9	—

SECONDARY outcome

Timeframe: 6 years

Population: The PRO evaluable population was defined as the participants from the SA population who completed a baseline assessment and at least one post-baseline assessment.

The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), global health status/quality of life, disease/treatment related symptoms (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, sleep disturbance, constipation, and diarrhoea), and the perceived financial impact of disease. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-C30 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher ("worse") symptom severity, higher ("better") functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=976 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 8/Day 1) (n=704)	-1.9 Units on a scale Standard Deviation 19.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 9/Day 1) (n=673)	-1.8 Units on a scale Standard Deviation 21.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 10/Day 1) (n=637)	-1.4 Units on a scale Standard Deviation 21.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 11/Day 1) (n=577)	-1.7 Units on a scale Standard Deviation 20.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 12/Day 1) (n=413)	-1.5 Units on a scale Standard Deviation 21.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 13/Day 1) (n=517)	-0.7 Units on a scale Standard Deviation 21.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 15/Day 1) (n=466)	-0.7 Units on a scale Standard Deviation 21.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 17/Day 1) (n=424)	-0.3 Units on a scale Standard Deviation 20.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 18/Day 1) (n=250)	-0.9 Units on a scale Standard Deviation 21.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 19/Day 1) (n=380)	-0.3 Units on a scale Standard Deviation 20.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 20/Day 1) (n=224)	-2.3 Units on a scale Standard Deviation 18.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 21/Day 1) (n=346)	-1.1 Units on a scale Standard Deviation 18.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 23/Day 1) (n=311)	0.8 Units on a scale Standard Deviation 17.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 24/Day 1) (n=157)	-1.3 Units on a scale Standard Deviation 17.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 25/Day 1) (n=297)	0.6 Units on a scale Standard Deviation 18.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 26/Day 1) (n=129)	-2.3 Units on a scale Standard Deviation 20.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 27/Day 1) (n=275)	1.9 Units on a scale Standard Deviation 17.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 28/Day 1) (n=121)	1.8 Units on a scale Standard Deviation 19.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 29/Day 1) (n=251)	2.5 Units on a scale Standard Deviation 18.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 30/Day 1) (n=109)	-0.5 Units on a scale Standard Deviation 17.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (End of treatment) (n=451)	4.0 Units on a scale Standard Deviation 25.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 3/Day 1) (n=880)	-16.0 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 4/Day 1) (n=836)	-15.7 Units on a scale Standard Deviation 27.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 5/Day 1) (n=810)	-15.5 Units on a scale Standard Deviation 27.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 6/Day 1) (n=779)	-15.5 Units on a scale Standard Deviation 27.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 7/Day 1) (n=739)	-16.0 Units on a scale Standard Deviation 29.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 8/Day 1) (n=705)	-15.9 Units on a scale Standard Deviation 28.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 9/Day 1) (n=673)	-15.5 Units on a scale Standard Deviation 28.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 10/Day 1) (n=637)	-15.1 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 11/Day 1) (n=577)	-14.6 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 12/Day 1) (n=414)	-13.6 Units on a scale Standard Deviation 29.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 13/Day 1) (n=517)	-13.8 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 14/Day 1) (n=357)	-13.9 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 15/Day 1) (n=466)	-12.1 Units on a scale Standard Deviation 27.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 16/Day 1) (n=296)	-12.5 Units on a scale Standard Deviation 27.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 17/Day 1) (n=424)	-10.6 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 18/Day 1) (n=250)	-11.1 Units on a scale Standard Deviation 27.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 19/Day 1) (n=380)	-10.8 Units on a scale Standard Deviation 24.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 20/Day 1) (n=224)	-11.0 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 21/Day 1) (n=346)	-10.1 Units on a scale Standard Deviation 25.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 22/Day 1) (n=182)	-7.7 Units on a scale Standard Deviation 26.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 24/Day 1) (n=157)	-8.8 Units on a scale Standard Deviation 27.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 25/Day 1) (n=297)	-8.8 Units on a scale Standard Deviation 24.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 26/Day 1) (n=129)	-12.5 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 27/Day 1) (n=275)	-7.6 Units on a scale Standard Deviation 25.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 28/Day 1) (n=121)	-7.9 Units on a scale Standard Deviation 32.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 29/Day 1) (n=251)	-8.1 Units on a scale Standard Deviation 24.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 30/Day 1) (n=109)	-7.5 Units on a scale Standard Deviation 29.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (End of treatment) (n=451)	-5.3 Units on a scale Standard Deviation 31.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (End of treatment) 9n=451)	-5.7 Units on a scale Standard Deviation 33.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 3/Day 1) (n=879)	6.6 Units on a scale Standard Deviation 18.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 17/Day 1) (n=424)	6.0 Units on a scale Standard Deviation 18.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 21/Day 1) (n=346)	5.7 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 24/Day 1) (n=156)	2.4 Units on a scale Standard Deviation 18.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 30/Day 1) (n=109)	2.8 Units on a scale Standard Deviation 21.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (End of treatment) (n=451)	0.1 Units on a scale Standard Deviation 25.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 7/Day 1) (n=734)	3.2 Units on a scale Standard Deviation 18.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 11/Day 1) (n=571)	3.0 Units on a scale Standard Deviation 18.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 12/Day 1) (n=411)	1.5 Units on a scale Standard Deviation 17.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 19/Day 1) (n=376)	0.1 Units on a scale Standard Deviation 19.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 16/Day 1) (n=293)	7.5 Units on a scale Standard Deviation 16.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 24/Day 1) (n=153)	4.4 Units on a scale Standard Deviation 19.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 9/Day 1) (n=671)	10.9 Units on a scale Standard Deviation 28.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 11/Day 1) (n=576)	10.0 Units on a scale Standard Deviation 29.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 14/Day 1) (n=358)	8.4 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 20/Day 1) (n=224)	5.8 Units on a scale Standard Deviation 25.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 22/Day 1) (n=182)	4.1 Units on a scale Standard Deviation 26.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 25/Day 1) (n=297)	2.2 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 6/Day 1) (n=773)	11.1 Units on a scale Standard Deviation 27.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 12/Day 1) (n=410)	10.3 Units on a scale Standard Deviation 26.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 13/Day 1) (n=512)	10.6 Units on a scale Standard Deviation 27.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 15/Day 1) (n=462)	10.1 Units on a scale Standard Deviation 28.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 26/Day 1) (n=126)	5.2 Units on a scale Standard Deviation 26.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 2/Day 1) (n=936)	-2.1 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 13/Day 1) (n=517)	-11.3 Units on a scale Standard Deviation 29.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 14/Day 1) (n=358)	-9.9 Units on a scale Standard Deviation 31.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 3/Day 1) (n=870)	10.9 Units on a scale Standard Deviation 33.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 6/Day 1) (n=771)	5.4 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 10/Day 1) (n=631)	3.8 Units on a scale Standard Deviation 30.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 17/Day 1) (n=420)	8.3 Units on a scale Standard Deviation 30.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 25/Day 1) (n=293)	10.9 Units on a scale Standard Deviation 29.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 26/Day 1) (n=126)	5.6 Units on a scale Standard Deviation 32.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 27/Day 1) (n=269)	8.3 Units on a scale Standard Deviation 30.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (End of treatment) (n=444)	8.9 Units on a scale Standard Deviation 33.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 5/Day 1) (n=805)	12.6 Units on a scale Standard Deviation 26.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 10/Day 1) (n=632)	11.1 Units on a scale Standard Deviation 26.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 15/Day 1) (n=461)	8.5 Units on a scale Standard Deviation 23.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 16/Day 1) (n=293)	10.0 Units on a scale Standard Deviation 22.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 19/Day 1) (n=376)	7.8 Units on a scale Standard Deviation 22.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 20/Day 1) (n=222)	6.8 Units on a scale Standard Deviation 22.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 21/Day 1) (n=340)	6.6 Units on a scale Standard Deviation 20.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 22/Day 1) (n=179)	6.8 Units on a scale Standard Deviation 24.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 23/Day 1) (n=305)	8.7 Units on a scale Standard Deviation 22.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 27/Day 1) (n=269)	8.3 Units on a scale Standard Deviation 24.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 7/Day 1) (n=737)	-13.8 Units on a scale Standard Deviation 27.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 18/Day 1) (n=248)	-11.5 Units on a scale Standard Deviation 27.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 2/Day 1) (n=936)	-4.8 Units on a scale Standard Deviation 21.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 5/Day 1) (n=810)	-12.0 Units on a scale Standard Deviation 24.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 18/Day 1) (N=250)	-10.4 Units on a scale Standard Deviation 25.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 3/Day 1) (n=871)	-4.2 Units on a scale Standard Deviation 25.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 21/Day 1) (n=339)	-4.2 Units on a scale Standard Deviation 25.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 6/Day 1) (n=778)	-13.3 Units on a scale Standard Deviation 31.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 28/Day 1) (n=121)	-6.9 Units on a scale Standard Deviation 32.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 4/Day 1) (n=836)	0.3 Units on a scale Standard Deviation 22.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 14/Day 1) (n=358)	-0.4 Units on a scale Standard Deviation 23.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 16/Day 1) (n=296)	-0.8 Units on a scale Standard Deviation 19.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 22/Day 1) (n=182)	0.2 Units on a scale Standard Deviation 19.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 2/Day 1) (n=935)	-13.1 Units on a scale Standard Deviation 26.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Pain (Cycle 23/Day 1) (n=311)	-7.4 Units on a scale Standard Deviation 26.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 2/Day 1) (n=936)	4.3 Units on a scale Standard Deviation 17.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 4/Day 1) (n=836)	8.2 Units on a scale Standard Deviation 19.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 5/Day 1) (n=810)	8.8 Units on a scale Standard Deviation 18.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 6/Day 1) (n=778)	9.5 Units on a scale Standard Deviation 18.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 7/Day 1) (n=739)	10.0 Units on a scale Standard Deviation 19.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 8/Day 1) (n= 704)	10.1 Units on a scale Standard Deviation 18.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 9/Day 1) (n= 673)	10.5 Units on a scale Standard Deviation 18.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 10/Day 1) (n= 637)	9.5 Units on a scale Standard Deviation 17.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 11/Day 1) (n=577)	9.1 Units on a scale Standard Deviation 17.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 12/Day 1) (n=412)	8.2 Units on a scale Standard Deviation 17.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 13/Day 1) (n=517)	8.7 Units on a scale Standard Deviation 18.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 14/Day 1) (n=358)	8.2 Units on a scale Standard Deviation 16.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 15/Day 1) (n=466)	7.3 Units on a scale Standard Deviation 19.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 16/Day 1) (n=295)	6.3 Units on a scale Standard Deviation 19.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 18/Day 1) (n=250)	6.1 Units on a scale Standard Deviation 18.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 19/Day 1) (n=380)	6.6 Units on a scale Standard Deviation 16.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 20/Day 1) (n=224)	5.1 Units on a scale Standard Deviation 16.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 22/Day 1) (n=182)	3.8 Units on a scale Standard Deviation 17.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 23/Day 1) (n=311)	3.7 Units on a scale Standard Deviation 17.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 25/Day 1) (n=296)	4.0 Units on a scale Standard Deviation 18.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 26/Day 1) (n=129)	5.3 Units on a scale Standard Deviation 18.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 27/Day 1) (n=275)	3.8 Units on a scale Standard Deviation 16.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 28/Day 1) (n=121)	3.6 Units on a scale Standard Deviation 20.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Physical Functioning (Cycle 29/Day 1) (n=251)	3.7 Units on a scale Standard Deviation 15.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive functioning (Cycle 2/Day 1) (n=930)	1.0 Units on a scale Standard Deviation 18.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 3/Day 1) (n=874)	2.1 Units on a scale Standard Deviation 19.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 4/Day 1) (n=829)	2.1 Units on a scale Standard Deviation 18.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 5/Day 1) (n=806)	2.3 Units on a scale Standard Deviation 18.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 6/Day 1) (n=773)	2.5 Units on a scale Standard Deviation 18.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 8/Day 1) (n=699)	3.3 Units on a scale Standard Deviation 18.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 9/Day 1) (n=667)	3.0 Units on a scale Standard Deviation 18.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 10/Day 1) (n=632)	2.7 Units on a scale Standard Deviation 19.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 13/Day 1) (n=512)	2.0 Units on a scale Standard Deviation 19.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 14/Day 1) (n=352)	1.2 Units on a scale Standard Deviation 17.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 15/Day 1) (n=462)	1.3 Units on a scale Standard Deviation 19.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 16/Day 1) (n=294)	-0.1 Units on a scale Standard Deviation 18.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 17/Day 1) (n=419)	0.0 Units on a scale Standard Deviation 19.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 18/Day 1) (n=247)	0.1 Units on a scale Standard Deviation 19.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 20/Day 1) (n=222)	0.9 Units on a scale Standard Deviation 18.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 21/Day 1) (n=340)	-0.1 Units on a scale Standard Deviation 17.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 22/Day 1) (n=179)	-1.1 Units on a scale Standard Deviation 17.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 23/Day 1) (n=305)	-0.3 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 24/Day 1) (n=154)	-3.6 Units on a scale Standard Deviation 21.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 25/Day 1) (n=293)	-1.3 Units on a scale Standard Deviation 18.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 26/Day 1) (n=127)	-0.3 Units on a scale Standard Deviation 20.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 27/Day 1) (n=269)	-0.9 Units on a scale Standard Deviation 17.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 28/Day 1) (n=120)	-0.6 Units on a scale Standard Deviation 20.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 29/Day 1) (n=247)	-0.2 Units on a scale Standard Deviation 16.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (Cycle 30/Day 1) (n=106)	-2.5 Units on a scale Standard Deviation 23.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Cognitive Functioning (End of treatment) (n=449)	-2.3 Units on a scale Standard Deviation 21.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 2/Day 1) (n=928)	5.5 Units on a scale Standard Deviation 18.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 3/Day 1) (n=873)	6.8 Units on a scale Standard Deviation 18.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 4/Day 1) (n=827)	8.2 Units on a scale Standard Deviation 18.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 5/Day 1) (n=804)	7.8 Units on a scale Standard Deviation 18.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 6/Day 1) (n=772)	8.6 Units on a scale Standard Deviation 18.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 7/Day 1) (n=731)	8.3 Units on a scale Standard Deviation 18.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 8/Day 1) (n=697)	9.2 Units on a scale Standard Deviation 18.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 9/Day 1) (n=665)	8.7 Units on a scale Standard Deviation 18.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 10/Day 1) (n=630)	8.5 Units on a scale Standard Deviation 18.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 11/Day 1) (n=571)	8.5 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 12/Day 1) (n=410)	8.4 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 13/Day 1) (n=511)	8.5 Units on a scale Standard Deviation 19.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 14/Day 1) (n=352)	7.9 Units on a scale Standard Deviation 16.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 15/Day 1) (n=461)	8.3 Units on a scale Standard Deviation 18.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 17/Day 1) (n=418)	6.9 Units on a scale Standard Deviation 19.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 18/Day 1) (n=246)	7.5 Units on a scale Standard Deviation 17.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 19/Day 1) (n=376)	7.4 Units on a scale Standard Deviation 18.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 20/Day 1) (n=221)	7.4 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 21/Day 1) (n=340)	6.7 Units on a scale Standard Deviation 17.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 22/Day 1) (n=178)	5.2 Units on a scale Standard Deviation 17.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 23/Day 1) (n=305)	6.6 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 25/Day 1) (n=293)	6.2 Units on a scale Standard Deviation 17.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 26/Day 1) (n=126)	7.5 Units on a scale Standard Deviation 18.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 27/Day 1) (n=269)	6.3 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 28/Day 1) (n=119)	4.1 Units on a scale Standard Deviation 19.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 29/Day 1) (n=247)	5.9 Units on a scale Standard Deviation 17.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (Cycle 30/Day 1) (n=105)	3.2 Units on a scale Standard Deviation 21.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Emotional Functioning (End of treatment) (n=448)	1.9 Units on a scale Standard Deviation 22.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 2/Day 1) (n=935)	4.2 Units on a scale Standard Deviation 25.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 3/Day 1) (n=879)	7.3 Units on a scale Standard Deviation 27.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 4/Day 1) (n=835)	9.3 Units on a scale Standard Deviation 28.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 5/Day 1) (n=809)	9.5 Units on a scale Standard Deviation 28.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 6/Day 1) (n=778)	10.5 Units on a scale Standard Deviation 28.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 7/Day 1) (n=738)	10.4 Units on a scale Standard Deviation 30.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 8/Day 1) (n=702)	10.8 Units on a scale Standard Deviation 28.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 10/Day 1) (n=635)	10.8 Units on a scale Standard Deviation 28.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 12/Day 1) (n=413)	8.4 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 13/Day 1) (n=516)	9.0 Units on a scale Standard Deviation 28.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 15/Day 1) (n=465)	8.8 Units on a scale Standard Deviation 28.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 16/Day 1) (n=296)	6.0 Units on a scale Standard Deviation 28.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 17/Day 1) (n=424)	6.1 Units on a scale Standard Deviation 30.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 18/Day 1) (n=250)	5.2 Units on a scale Standard Deviation 27.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 19/Day 1) (n=380)	8.0 Units on a scale Standard Deviation 27.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 21/Day 1) (n=346)	5.3 Units on a scale Standard Deviation 27.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 23/Day 1) (n=311)	3.2 Units on a scale Standard Deviation 27.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 24/Day 1) (n=157)	2.7 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 26/Day 1) (n=129)	6.1 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 27/Day 1) (n=275)	2.4 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 28/Day 1) (n=121)	1.5 Units on a scale Standard Deviation 30.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 29/Day 1)(n=251)	1.6 Units on a scale Standard Deviation 24.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (Cycle 30/Day 1) (n=109)	1.1 Units on a scale Standard Deviation 34.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Role Functioning (End of treatment) (n=451)	-1.6 Units on a scale Standard Deviation 31.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 2/Day 1) (n=928)	6.8 Units on a scale Standard Deviation 25.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 3/Day 1) (n=872)	9.1 Units on a scale Standard Deviation 26.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 4/Day 1) (n=828)	10.4 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 5/Day 1) (n=805)	10.6 Units on a scale Standard Deviation 26.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 7/Day 1) (n=733)	12.1 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 8/Day 1) (n=698)	12.3 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 9/Day 1) (n=666)	12.0 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 10/Day 1) (n=631)	11.8 Units on a scale Standard Deviation 26.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 11/Day 1) (n=570)	12.1 Units on a scale Standard Deviation 27.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 14/Day 1) (n=352)	10.4 Units on a scale Standard Deviation 25.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 16/Day 1) (n=293)	9.0 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 17/Day 1) (n=418)	8.8 Units on a scale Standard Deviation 26.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 18/Day 1) (n=246)	6.6 Units on a scale Standard Deviation 25.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 19/Day 1) (n=376)	8.0 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 20/Day 1) (n=221)	5.7 Units on a scale Standard Deviation 23.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 21/Day 1) (n=340)	6.7 Units on a scale Standard Deviation 26.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 22/Day 1) (n=178)	5.3 Units on a scale Standard Deviation 22.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 23/Day 1) (n=305)	7.0 Units on a scale Standard Deviation 24.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 24/Day 1) (n=153)	3.6 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 25/Day 1) (n=293)	4.4 Units on a scale Standard Deviation 25.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 27/Day 1) (n=269)	5.3 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 28/Day 1) (n=119)	2.1 Units on a scale Standard Deviation 31.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 29/Day 1) (n=247)	6.6 Units on a scale Standard Deviation 24.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (Cycle 30/Day 1) (n=105)	1.6 Units on a scale Standard Deviation 29.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Social Functioning (End of treatment) (n=449)	2.7 Units on a scale Standard Deviation 31.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 3/Day 1) (n=877)	-6.3 Units on a scale Standard Deviation 31.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 4/Day 1) (n=833)	-9.1 Units on a scale Standard Deviation 31.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 5/Day 1) (n=810)	-10.4 Units on a scale Standard Deviation 31.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 6/Day 1) (n=778)	-11.4 Units on a scale Standard Deviation 32.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 7/Day 1) (n=738)	-11.4 Units on a scale Standard Deviation 32.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 8/Day 1) (n=704)	-11.5 Units on a scale Standard Deviation 32.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 9/Day 1) (n=673)	-11.7 Units on a scale Standard Deviation 32.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 10/Day 1) (n=637)	-11.9 Units on a scale Standard Deviation 30.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 11/Day 1) (n=577)	-11.2 Units on a scale Standard Deviation 30.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 12/Day 1) (n=413)	-9.1 Units on a scale Standard Deviation 30.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 15/Day 1) (n=466)	-10.5 Units on a scale Standard Deviation 30.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 16/Day 1) (n=296)	-10.4 Units on a scale Standard Deviation 32.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 17/Day 1) (n=424)	-8.6 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 18/Day 1) (n=250)	-10.1 Units on a scale Standard Deviation 31.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 19/Day 1) (n=380)	-8.9 Units on a scale Standard Deviation 30.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 20/Day 1) (n=224)	-12.8 Units on a scale Standard Deviation 29.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 21/Day 1) (n=346)	-7.5 Units on a scale Standard Deviation 30.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 22/Day 1) (n=181)	-9.2 Units on a scale Standard Deviation 27.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 23/Day 1) (n=310)	-4.9 Units on a scale Standard Deviation 28.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 24/Day 1) (n=157)	-10.9 Units on a scale Standard Deviation 30.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 25/Day 1) (n=297)	-4.6 Units on a scale Standard Deviation 29.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 26/Day 1) (n=129)	-12.1 Units on a scale Standard Deviation 32.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 27/Day 1) (n=275)	-4.2 Units on a scale Standard Deviation 29.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 28/Day 1) (n=121)	-6.6 Units on a scale Standard Deviation 34.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 29/Day 1) (n=251)	-3.2 Units on a scale Standard Deviation 27.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (Cycle 30/Day 1) (n=109)	-7.6 Units on a scale Standard Deviation 29.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Appetite loss (End of treatment) (n=451)	-0.0 Units on a scale Standard Deviation 36.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 2/Day 1) (n=929)	15.4 Units on a scale Standard Deviation 32.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 4/Day 1) (n=827)	7.0 Units on a scale Standard Deviation 31.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 5/Day 1) (n=804)	5.5 Units on a scale Standard Deviation 30.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 7/Day 1) (n=732)	4.7 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 8/Day 1) (n=698)	4.5 Units on a scale Standard Deviation 29.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 9/Day 1) (n=665)	5.0 Units on a scale Standard Deviation 29.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 11/Day 1) (n=571)	5.2 Units on a scale Standard Deviation 29.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 12/Day 1) (n=410)	6.4 Units on a scale Standard Deviation 29.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 13/Day 1) (n=513)	5.2 Units on a scale Standard Deviation 29.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 14/Day 1) (n=349)	5.0 Units on a scale Standard Deviation 28.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 15/Day 1) (n=464)	6.0 Units on a scale Standard Deviation 30.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 16/Day 1) (n=291)	4.4 Units on a scale Standard Deviation 29.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 18/Day 1) (n=246)	6.0 Units on a scale Standard Deviation 30.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 19/Day 1) (n=376)	7.4 Units on a scale Standard Deviation 30.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 20/Day 1) (n=221)	5.9 Units on a scale Standard Deviation 33.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 21/Day 1) (n=340)	7.7 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 22/Day 1) (n=178)	6.2 Units on a scale Standard Deviation 31.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 23/Day 1) (n=306)	9.7 Units on a scale Standard Deviation 31.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 24/Day 1) (n=154)	9.0 Units on a scale Standard Deviation 34.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 28/Day 1) (n=119)	9.8 Units on a scale Standard Deviation 31.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 29/Day 1) (n=247)	7.8 Units on a scale Standard Deviation 29.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Constipation (Cycle 30/Day 1) (n=105)	11.7 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 2/Day 1) (n=927)	11.4 Units on a scale Standard Deviation 25.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 3/Day 1) (n=872)	12.8 Units on a scale Standard Deviation 26.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 4/Day 1) (n=826)	11.7 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 6/Day 1) (n=772)	11.6 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 7/Day 1) (n=732)	10.9 Units on a scale Standard Deviation 26.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 8/Day 1) (n=698)	9.8 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 9/Day 1) (n=665)	10.5 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 11/Day 1) (n=570)	10.1 Units on a scale Standard Deviation 25.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 12/Day 1) (n=411)	8.1 Units on a scale Standard Deviation 25.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 13/Day 1) (n=512)	8.8 Units on a scale Standard Deviation 24.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 14/Day 1) (n=352)	10.1 Units on a scale Standard Deviation 22.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 17/Day 1) (n=419)	8.6 Units on a scale Standard Deviation 23.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 18/Day 1) (n=247)	7.4 Units on a scale Standard Deviation 22.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 24/Day 1) (n=154)	6.4 Units on a scale Standard Deviation 23.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 25/Day 1) (n=293)	10.1 Units on a scale Standard Deviation 23.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 26/Day 1) (n=127)	5.0 Units on a scale Standard Deviation 23.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 28/Day 1) (n=119)	5.6 Units on a scale Standard Deviation 20.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 29/Day 1) (n=247)	9.7 Units on a scale Standard Deviation 22.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (Cycle 30/Day 1) (n=106)	10.1 Units on a scale Standard Deviation 25.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Diarrhea (End of treatment) (n=449)	5.9 Units on a scale Standard Deviation 24.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 2/Day 1) (n=933)	-9.8 Units on a scale Standard Deviation 26.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 3/Day 1) (n=876)	-11.4 Units on a scale Standard Deviation 28.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 4/Day 1) (n=834)	-12.3 Units on a scale Standard Deviation 28.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 5/Day 1) (n=808)	-12.2 Units on a scale Standard Deviation 27.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 6/Day 1) (n=776)	-13.7 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 8/Day 1) (n=702)	-13.8 Units on a scale Standard Deviation 28.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 9/Day 1) (n=671)	-13.3 Units on a scale Standard Deviation 27.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 10/Day 1) (n=635)	-13.4 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 11/Day 1) (n=575)	-15.0 Units on a scale Standard Deviation 27.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 12/Day 1) (n=411)	-13.1 Units on a scale Standard Deviation 26.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 13/Day 1) (n=515)	-13.1 Units on a scale Standard Deviation 28.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 14/Day 1) (n=356)	-12.7 Units on a scale Standard Deviation 27.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 15/Day 1) (n=463)	-12.6 Units on a scale Standard Deviation 28.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 16/Day 1) (n=295)	-12.2 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 17/Day 1) (n=421)	-11.8 Units on a scale Standard Deviation 27.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 19/Day 1) (n=377)	-14.2 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 20/Day 1) (n=222)	-9.2 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 21/Day 1) (n=344)	-13.4 Units on a scale Standard Deviation 27.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 22/Day 1) (n=181)	-8.8 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 23/Day 1) (n=309)	-10.9 Units on a scale Standard Deviation 26.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 24/Day 1) (n=156)	-8.5 Units on a scale Standard Deviation 27.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 25/Day 1) (n=295)	-10.5 Units on a scale Standard Deviation 26.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 26/Day 1) (n=129)	-10.1 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 27/Day 1) (n=273)	-9.3 Units on a scale Standard Deviation 24.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 28/Day 1) (n=121)	-12.1 Units on a scale Standard Deviation 28.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 29/Day 1) (n=249)	-8.8 Units on a scale Standard Deviation 25.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (Cycle 30/Day 1) (n=109)	-11.6 Units on a scale Standard Deviation 27.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Dyspnoea (End of treatment) (n=450)	-4.2 Units on a scale Standard Deviation 32.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 3/Day 1) (n=879)	-8.9 Units on a scale Standard Deviation 23.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 4/Day 1) (n=836)	-11.4 Units on a scale Standard Deviation 24.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 6/Day 1) (n=778)	-13.7 Units on a scale Standard Deviation 24.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 7/Day 1) (n=739)	-14.0 Units on a scale Standard Deviation 24.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 8/Day 1) (n=704)	-15.3 Units on a scale Standard Deviation 23.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 9/Day 1) (n=671)	-14.9 Units on a scale Standard Deviation 24.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 10/Day 1) (n=637)	-14.4 Units on a scale Standard Deviation 24.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 11/Day 1) (n=577)	-13.7 Units on a scale Standard Deviation 24.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 12/Day 1) (n=413)	-12.2 Units on a scale Standard Deviation 23.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 13/Day 1) (n=517)	-13.4 Units on a scale Standard Deviation 23.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 14/Day 1) (n=358)	-13.2 Units on a scale Standard Deviation 22.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 15/Day 1) (n=466)	-13.1 Units on a scale Standard Deviation 23.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 16/Day 1) (n=296)	-11.3 Units on a scale Standard Deviation 24.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 17/Day 1) (n=424)	-11.3 Units on a scale Standard Deviation 24.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 19/Day 1) (n=380)	-11.9 Units on a scale Standard Deviation 23.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 20/Day 1) (n=224)	-10.6 Units on a scale Standard Deviation 23.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 21/Day 1) (n=346)	-11.0 Units on a scale Standard Deviation 25.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 22/Day 1) (n=182)	-8.4 Units on a scale Standard Deviation 23.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 23/Day 1) (n=311)	-8.7 Units on a scale Standard Deviation 23.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 24/Day 1) (n=157)	-6.7 Units on a scale Standard Deviation 24.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 25/Day 1) (n=297)	-7.9 Units on a scale Standard Deviation 23.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 26/Day 1) (n=129)	-12.1 Units on a scale Standard Deviation 24.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 27/Day 1) (n=275)	-7.0 Units on a scale Standard Deviation 22.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 28/Day 1) (n=121)	-6.7 Units on a scale Standard Deviation 25.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 29/Day 1) (n=251)	-7.1 Units on a scale Standard Deviation 22.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (Cycle 30/Day 1) (n=109)	-7.2 Units on a scale Standard Deviation 27.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Fatigue (End of treatment) (n=451)	-5.3 Units on a scale Standard Deviation 27.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 2/Day 1) (n=928)	-4.6 Units on a scale Standard Deviation 24.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 4/Day 1) (n=827)	-5.9 Units on a scale Standard Deviation 25.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 5/Day 1) (n=803)	-5.1 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 6/Day 1) (n=772)	-5.5 Units on a scale Standard Deviation 25.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 7/Day 1) (n=732)	-6.2 Units on a scale Standard Deviation 25.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 8/Day 1) (n=697)	-6.4 Units on a scale Standard Deviation 26.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 9/Day 1) (n=663)	-5.8 Units on a scale Standard Deviation 25.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 10/Day 1) (n=631)	-7.4 Units on a scale Standard Deviation 25.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 11/Day 1) (n=569)	-6.6 Units on a scale Standard Deviation 25.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 12/Day 1) (n=410)	-4.8 Units on a scale Standard Deviation 25.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 13/Day 1) (n=512)	-6.3 Units on a scale Standard Deviation 25.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 14/Day 1) (n=352)	-5.8 Units on a scale Standard Deviation 25.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 15/Day 1) (n=461)	-6.1 Units on a scale Standard Deviation 26.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 16/Day 1) (n=294)	-4.0 Units on a scale Standard Deviation 23.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 17/Day 1) (n=418)	-5.5 Units on a scale Standard Deviation 26.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 18/Day 1) (n=247)	-3.8 Units on a scale Standard Deviation 25.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 19/Day 1) (n=376)	-5.9 Units on a scale Standard Deviation 26.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 20/Day 1) (n=220)	-5.2 Units on a scale Standard Deviation 25.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 22/Day 1) (n=177)	-2.1 Units on a scale Standard Deviation 23.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 23/Day 1) (n=304)	-4.4 Units on a scale Standard Deviation 24.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 24/Day 1) (n=153)	-2.8 Units on a scale Standard Deviation 27.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 25/Day 1) (n=292)	-4.6 Units on a scale Standard Deviation 24.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 26/Day 1) (n=126)	-2.9 Units on a scale Standard Deviation 26.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 27/Day 1) (n=268)	-4.8 Units on a scale Standard Deviation 25.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 28/Day 1) (n=119)	-4.2 Units on a scale Standard Deviation 29.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 29/Day 1) (n=247)	-5.5 Units on a scale Standard Deviation 25.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (Cycle 30/Day 1) (n=105)	-3.5 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Financial Difficulties (End of treatment) (n=447)	-2.2 Units on a scale Standard Deviation 27.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 2/Day 1) (n=934)	-7.6 Units on a scale Standard Deviation 29.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 3/Day 1) (n=878)	-11.3 Units on a scale Standard Deviation 30.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 4/Day 1) (n=833)	-13.0 Units on a scale Standard Deviation 29.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 5/Day 1) (n=808)	-12.8 Units on a scale Standard Deviation 29.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 7/Day 1) (n=739)	-13.9 Units on a scale Standard Deviation 29.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 8/Day 1) (n=703)	-12.6 Units on a scale Standard Deviation 29.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 9/Day 1) (n=673)	-13.2 Units on a scale Standard Deviation 28.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 10/Day 1) (n=637)	-13.2 Units on a scale Standard Deviation 29.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 11/Day 1) (n=576)	-12.2 Units on a scale Standard Deviation 30.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 12/Day 1) (n=413)	-11.3 Units on a scale Standard Deviation 29.7	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 13/Day 1) (n=516)	-13.0 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 14/Day 1) (n=358)	-11.7 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 15/Day 1) (n=464)	-12.4 Units on a scale Standard Deviation 30.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 16/Day 1) (n=296)	-10.9 Units on a scale Standard Deviation 31.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 17/Day 1) (n=424)	-10.8 Units on a scale Standard Deviation 29.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 18/Day 1) (n=250)	-10.4 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 19/Day 1) (n=379)	-12.6 Units on a scale Standard Deviation 28.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 20/Day 1) (n=224)	-11.5 Units on a scale Standard Deviation 27.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 21/Day 1) (n=346)	-10.2 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 22/Day 1) (n=182)	-7.9 Units on a scale Standard Deviation 25.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 23/Day 1) (n=311)	-10.5 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 24/Day 1) (n=157)	-5.7 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 25/Day 1) (n=296)	-7.7 Units on a scale Standard Deviation 28.8	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 26/Day 1) (n=129)	-10.9 Units on a scale Standard Deviation 29.2	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 27/Day 1) (n=274)	-10.1 Units on a scale Standard Deviation 27.4	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 29/Day 1) (n=251)	-8.4 Units on a scale Standard Deviation 28.5	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Insomnia (Cycle 30/Day 1) (n=109)	-11.3 Units on a scale Standard Deviation 32.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 2/Day 1) (n=936)	6.2 Units on a scale Standard Deviation 23.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 3/Day 1) (n=879)	2.4 Units on a scale Standard Deviation 23.3	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 5/Day 1) (n=810)	-0.4 Units on a scale Standard Deviation 21.1	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 6/Day 1) (n=779)	-1.6 Units on a scale Standard Deviation 19.9	—
Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores Nausea and Vomiting (Cycle 7/Day 1) (n=739)	-2.3 Units on a scale Standard Deviation 21.0	—

SECONDARY outcome

Timeframe: 6 years

Population: The PRO evaluable population was defined as the participants from the SA population who completed a baseline assessment and at least one post-baseline assessment.

The QLQ-LC13 consists of 1 multi-item scale and 9 single items that assess specific symptoms (dyspnoea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of lung cancer patients. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-LC13 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher ("worse") symptom severity, higher ("better") functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=976 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 2/Day 1) (n=920)	-9.1 Units on a scale Standard Deviation 29.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 3/Day 1) (n=870)	-10.2 Units on a scale Standard Deviation 31.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 4/Day 1) (n=829)	-11.6 Units on a scale Standard Deviation 30.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 5/Day 1) (n=805)	-12.2 Units on a scale Standard Deviation 32.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 6/Day 1) (n=770)	-10.5 Units on a scale Standard Deviation 30.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 7/Day 1) (n=734)	-11.9 Units on a scale Standard Deviation 32.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 8/Day 1) (n=700)	-11.9 Units on a scale Standard Deviation 33.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 9/Day 1) (n=667)	-11.3 Units on a scale Standard Deviation 34.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 10/Day 1) (n=633)	-10.8 Units on a scale Standard Deviation 33.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 11/Day 1) (n=574)	-11.3 Units on a scale Standard Deviation 34.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 12/Day 1) (n=409)	-7.8 Units on a scale Standard Deviation 34.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 13/Day 1) (n=512)	-10.8 Units on a scale Standard Deviation 35.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 14/Day 1) (n=353)	-8.2 Units on a scale Standard Deviation 36.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 15/Day 1) (n=462)	-11.8 Units on a scale Standard Deviation 34.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 16/Day 1) (n=293)	-7.7 Units on a scale Standard Deviation 34.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 17/Day 1) (n=419)	-9.5 Units on a scale Standard Deviation 32.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 18/Day 1) (n=247)	-6.4 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 19/Day 1) (n=377)	-8.9 Units on a scale Standard Deviation 34.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 21/Day 1) (n=342)	-7.8 Units on a scale Standard Deviation 32.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 22/Day 1) (n=180)	-7.6 Units on a scale Standard Deviation 35.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 23/Day 1) (n=310)	-7.0 Units on a scale Standard Deviation 33.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 25/Day 1) (n=293)	-8.2 Units on a scale Standard Deviation 31.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 26/Day 1) (n=126)	-4.5 Units on a scale Standard Deviation 31.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 27/Day 1) (n=271)	-8.5 Units on a scale Standard Deviation 31.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 28/Day 1) (n=119)	-3.9 Units on a scale Standard Deviation 33.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (End of treatment) (n=447)	-9.9 Units on a scale Standard Deviation 35.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 2/Day 1) (n=926)	-12.9 Units on a scale Standard Deviation 28.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 3/Day 1) (n=879)	-15.5 Units on a scale Standard Deviation 31.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 4/Day 1) (n=832)	-17.7 Units on a scale Standard Deviation 31.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 5/Day 1) (n=807)	-17.3 Units on a scale Standard Deviation 31.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 7/Day 1) (n=735)	-20.1 Units on a scale Standard Deviation 32.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 8/Day 1) (n=703)	-20.8 Units on a scale Standard Deviation 31.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 9/Day 1) (n=669)	-20.2 Units on a scale Standard Deviation 30.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 10/Day 1) (n=636)	-19.9 Units on a scale Standard Deviation 32.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 11/Day 1) (n=575)	-19.9 Units on a scale Standard Deviation 31.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 12/Day 1) (n=414)	-19.2 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 14/Day 1) (n=355)	-17.9 Units on a scale Standard Deviation 32.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 15/Day 1) (n=461)	-17.8 Units on a scale Standard Deviation 31.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 16/Day 1) (n=294)	-17.3 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 17/Day 1) (n=421)	-18.4 Units on a scale Standard Deviation 32.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 18/Day 1) (n=249)	-16.9 Units on a scale Standard Deviation 33.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 19/Day 1) (n=379)	-18.8 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 20/Day 1) (n=222)	-18.3 Units on a scale Standard Deviation 32.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 21/Day 1) (n=343)	-18.0 Units on a scale Standard Deviation 31.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 22/Day 1) (n=181)	-16.7 Units on a scale Standard Deviation 33.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 23/Day 1) (n=311)	-18.4 Units on a scale Standard Deviation 32.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 24/Day 1) (n=155)	-18.9 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 25/Day 1) (n=294)	-18.1 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 26/Day 1) (n=125)	-21.9 Units on a scale Standard Deviation 30.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 27/Day 1) (n=272)	-17.8 Units on a scale Standard Deviation 32.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (End of treatment) (n=452)	-11.1 Units on a scale Standard Deviation 33.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 2/Day 1) (n=926)	0.0 Units on a scale Standard Deviation 19.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 4/Day 1) (n=831)	-2.2 Units on a scale Standard Deviation 20.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 5/Day 1) (n=807)	-2.3 Units on a scale Standard Deviation 20.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 7/Day 1) (n=737)	-3.1 Units on a scale Standard Deviation 20.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 8/Day 1) (n=702)	-3.1 Units on a scale Standard Deviation 18.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 9/Day 1) (n=670)	-2.7 Units on a scale Standard Deviation 20.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 11/Day 1) (n=577)	-3.0 Units on a scale Standard Deviation 19.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 12/Day 1) (n=414)	-2.7 Units on a scale Standard Deviation 18.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 13/Day 1) (n=513)	-3.1 Units on a scale Standard Deviation 17.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 14/Day 1) (n=355)	-1.7 Units on a scale Standard Deviation 18.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 16/Day 1) (n=294)	-1.3 Units on a scale Standard Deviation 20.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 17/Day 1) (n=422)	-2.2 Units on a scale Standard Deviation 19.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 18/Day 1) (n=249)	-2.5 Units on a scale Standard Deviation 18.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 19/Day 1) (n=378)	-2.0 Units on a scale Standard Deviation 17.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 21/Day 1) (n=344)	-2.5 Units on a scale Standard Deviation 18.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 22/Day 1) (n=182)	-1.8 Units on a scale Standard Deviation 19.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 24/Day 1) (n=156)	-1.4 Units on a scale Standard Deviation 16.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 25/Day 1) (n=295)	-2.8 Units on a scale Standard Deviation 17.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 26/Day 1) (n=126)	-1.1 Units on a scale Standard Deviation 15.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 28/Day 1) (n=120)	-1.4 Units on a scale Standard Deviation 16.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 29/Day 1) (n=248)	-1.5 Units on a scale Standard Deviation 16.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 30/Day 1) (n=107)	-0.9 Units on a scale Standard Deviation 18.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (End of treatment) (n=449)	1.9 Units on a scale Standard Deviation 23.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 2/Day 1) (n=928)	-8.0 Units on a scale Standard Deviation 19.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 3/Day 1) (n=878)	-9.7 Units on a scale Standard Deviation 21.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 4/Day 1) (n=833)	-10.7 Units on a scale Standard Deviation 21.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 5/Day 1) (n=809)	-10.6 Units on a scale Standard Deviation 21.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 6/Day 1) (n=775)	-10.6 Units on a scale Standard Deviation 21.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 7/Day 1) (n=737)	-11.1 Units on a scale Standard Deviation 21.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 8/Day 1) (n=704)	-12.0 Units on a scale Standard Deviation 20.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 9/Day 1) (n=669)	-11.0 Units on a scale Standard Deviation 20.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 10/Day 1) (n=637)	-10.7 Units on a scale Standard Deviation 21.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 12/Day 1) (n=414)	-9.0 Units on a scale Standard Deviation 20.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 13/Day 1) (n=514)	-9.8 Units on a scale Standard Deviation 21.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 14/Day 1) (n=354)	-9.2 Units on a scale Standard Deviation 20.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 15/Day 1) (n=463)	-8.9 Units on a scale Standard Deviation 21.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 16/Day 1) (n=293)	-7.7 Units on a scale Standard Deviation 21.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 17/Day 1) (n=421)	-7.3 Units on a scale Standard Deviation 20.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 18/Day 1) (n=249)	-6.9 Units on a scale Standard Deviation 21.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 19/Day 1) (n=379)	-8.6 Units on a scale Standard Deviation 19.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 20/Day 1) (n=223)	-5.8 Units on a scale Standard Deviation 19.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 21/Day 1) (n=344)	-7.8 Units on a scale Standard Deviation 19.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 22/Day 1) (n=182)	-5.6 Units on a scale Standard Deviation 18.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 23/Day 1) (n=311)	-6.1 Units on a scale Standard Deviation 19.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 24/Day 1) (n=156)	-6.2 Units on a scale Standard Deviation 18.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 25/Day 1) (n=295)	-6.1 Units on a scale Standard Deviation 19.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 26/Day 1) (n=126)	-6.6 Units on a scale Standard Deviation 19.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 27/Day 1) (n=273)	-5.7 Units on a scale Standard Deviation 19.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 29/Day 1) (n=249)	-3.9 Units on a scale Standard Deviation 19.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 30/Day 1) (n=107)	-4.6 Units on a scale Standard Deviation 17.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (End of treatment) (n=448)	-3.0 Units on a scale Standard Deviation 25.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 2/Day 1) (n=925)	-2.6 Units on a scale Standard Deviation 12.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 3/Day 1) (n=879)	-3.0 Units on a scale Standard Deviation 12.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 4/Day 1) (n=833)	-2.9 Units on a scale Standard Deviation 12.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 5/Day 1) (n=808)	-2.6 Units on a scale Standard Deviation 12.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 6/Day 1) (n=774)	-2.8 Units on a scale Standard Deviation 12.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 7/Day 1) (n=735)	-2.9 Units on a scale Standard Deviation 12.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 8/Day 1) (n=703)	-3.1 Units on a scale Standard Deviation 11.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 9/Day 1) (n=669)	-3.0 Units on a scale Standard Deviation 11.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 10/Day 1) (n=635)	-2.6 Units on a scale Standard Deviation 11.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 11/Day 1) (n=576)	-2.7 Units on a scale Standard Deviation 11.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 12/Day 1) (n=413)	-2.6 Units on a scale Standard Deviation 10.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 14/Day 1) (n=354)	-2.7 Units on a scale Standard Deviation 11.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 16/Day 1) (n=294)	-2.5 Units on a scale Standard Deviation 11.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 17/Day 1) (n=420)	-1.9 Units on a scale Standard Deviation 11.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 18/Day 1) (n=249)	-2.4 Units on a scale Standard Deviation 12.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 19/Day 1) (n=378)	-2.1 Units on a scale Standard Deviation 11.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 20/Day 1) (n=223)	-2.4 Units on a scale Standard Deviation 13.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 21/Day 1) (n=342)	-2.5 Units on a scale Standard Deviation 11.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 22/Day 1) (n=182)	-2.9 Units on a scale Standard Deviation 11.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 23/Day 1) (n=309)	-2.7 Units on a scale Standard Deviation 12.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 24/Day 1) (n=156)	-2.4 Units on a scale Standard Deviation 12.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 25/Day 1) (n=294)	-2.8 Units on a scale Standard Deviation 12.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 26/Day 1) (n=126)	-3.2 Units on a scale Standard Deviation 12.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 27/Day 1) (n=272)	-2.9 Units on a scale Standard Deviation 11.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 28/Day 1) (n=119)	-3.1 Units on a scale Standard Deviation 12.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 29/Day 1) (n=248)	-1.7 Units on a scale Standard Deviation 12.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 30/Day 1) (n=107)	-2.8 Units on a scale Standard Deviation 11.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (End of treatment) (n=451)	-1.4 Units on a scale Standard Deviation 15.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 2/Day 1) (n=926)	-9.6 Units on a scale Standard Deviation 26.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 3/Day 1) (n=876)	-12.2 Units on a scale Standard Deviation 27.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 4/Day 1) (n=832)	-12.5 Units on a scale Standard Deviation 28.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 5/Day 1) (n=807)	-11.7 Units on a scale Standard Deviation 27.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 6/Day 1) (n=773)	-11.6 Units on a scale Standard Deviation 26.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 7/Day 1) (n=738)	-11.3 Units on a scale Standard Deviation 28.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 8/Day 1) (n=702)	-11.7 Units on a scale Standard Deviation 28.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 9/Day 1) (n=669)	-11.9 Units on a scale Standard Deviation 28.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 10/Day 1) (n=635)	-11.3 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 11/Day 1) (n=576)	-12.1 Units on a scale Standard Deviation 27.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 12/Day 1) (n=414)	-11.0 Units on a scale Standard Deviation 27.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 13/Day 1) (n=513)	-10.9 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 14/Day 1) (n=355)	-11.3 Units on a scale Standard Deviation 27.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 15/Day 1) (n=461)	-10.3 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 17/Day 1) (n=421)	-8.2 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 18/Day 1) (n=249)	-9.4 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 19/Day 1) (n=379)	-9.1 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 20/Day 1) (n=222)	-7.4 Units on a scale Standard Deviation 27.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 21/Day 1) (n=344)	-9.0 Units on a scale Standard Deviation 27.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 24/Day 1) (n=155)	-9.7 Units on a scale Standard Deviation 30.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 25/Day 1) (n=295)	-9.2 Units on a scale Standard Deviation 26.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 26/Day 1) (n=126)	-10.8 Units on a scale Standard Deviation 33.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 27/Day 1) (n=274)	-8.6 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 28/Day 1) (n=119)	-8.7 Units on a scale Standard Deviation 29.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 29/Day 1) (n=248)	-7.9 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 30/Day 1) (n=107)	-8.1 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (End of treatment) (n=445)	-5.8 Units on a scale Standard Deviation 30.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 2/Day 1) (n=928)	-9.5 Units on a scale Standard Deviation 23.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 3/Day 1) (n=875)	-11.9 Units on a scale Standard Deviation 25.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 4/Day 1) (n=833)	-12.1 Units on a scale Standard Deviation 26.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 5/Day 1) (n=808)	-11.8 Units on a scale Standard Deviation 25.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 6/Day 1) (n=774)	-12.1 Units on a scale Standard Deviation 25.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 8/Day 1) (n=703)	-13.2 Units on a scale Standard Deviation 25.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 9/Day 1) (n=665)	-13.1 Units on a scale Standard Deviation 25.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 10/Day 1) (n=633)	-12.9 Units on a scale Standard Deviation 26.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 11/Day 1) (n=574)	-12.0 Units on a scale Standard Deviation 25.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 12/Day 1) (n=414)	-10.7 Units on a scale Standard Deviation 25.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 14/Day 1) (n=355)	-11.5 Units on a scale Standard Deviation 24.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 16/Day 1) (n=294)	-11.0 Units on a scale Standard Deviation 23.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 17/Day 1) (n=421)	-11.6 Units on a scale Standard Deviation 23.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 21/Day 1) (n=343)	-11.9 Units on a scale Standard Deviation 23.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 22/Day 1) (n=182)	-10.1 Units on a scale Standard Deviation 21.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 23/Day 1) (n=308)	-10.8 Units on a scale Standard Deviation 24.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 24/Day 1) (n=156)	-7.1 Units on a scale Standard Deviation 26.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 25/Day 1) (n=293)	-10.2 Units on a scale Standard Deviation 22.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 30/Day 1) (n=107)	-5.3 Units on a scale Standard Deviation 26.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (End of treatment) (n=451)	-6.7 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 2/Day 1) (n=893)	-10.0 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 4/Day 1) (n=806)	-13.5 Units on a scale Standard Deviation 31.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 5/Day 1) (n=793)	-12.2 Units on a scale Standard Deviation 30.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 6/Day 1) (n=752)	-12.5 Units on a scale Standard Deviation 30.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 7/Day 1) (n=715)	-11.8 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 8/Day 1) (n=680)	-11.7 Units on a scale Standard Deviation 30.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 9/Day 1) (n=650)	-13.1 Units on a scale Standard Deviation 29.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 10/Day 1) (n=616)	-12.1 Units on a scale Standard Deviation 30.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 11/Day 1) (n=562)	-10.8 Units on a scale Standard Deviation 29.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 12/Day 1) (n=399)	-11.6 Units on a scale Standard Deviation 30.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 13/Day 1) (n=499)	-9.9 Units on a scale Standard Deviation 30.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 14/Day 1) (n=342)	-11.5 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 15/Day 1) (n=451)	-10.1 Units on a scale Standard Deviation 28.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 16/Day 1) (n=282)	-9.6 Units on a scale Standard Deviation 30.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 17/Day 1) (n=411)	-8.8 Units on a scale Standard Deviation 28.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 18/Day 1) (n=239)	-8.6 Units on a scale Standard Deviation 31.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 19/Day 1) (n=370)	-8.8 Units on a scale Standard Deviation 29.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 20/Day 1) (n=210)	-9.4 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 21/Day 1) (n=337)	-8.2 Units on a scale Standard Deviation 28.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 22/Day 1) (n=176)	-10.4 Units on a scale Standard Deviation 30.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 23/Day 1) (n=300)	-6.6 Units on a scale Standard Deviation 29.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 24/Day 1) (n=149)	-7.8 Units on a scale Standard Deviation 35.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 25/Day 1) (n=286)	-7.2 Units on a scale Standard Deviation 30.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 26/Day 1) (n=121)	-8.8 Units on a scale Standard Deviation 34.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 27/Day 1) (n=267)	-5.9 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 28/Day 1) (n=116)	-3.2 Units on a scale Standard Deviation 34.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 29/Day 1) (n=242)	-6.3 Units on a scale Standard Deviation 27.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 30/Day 1) (n=102)	-6.5 Units on a scale Standard Deviation 34.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (End of treatment) (n=427)	-4.6 Units on a scale Standard Deviation 34.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 2/Day 1) (n=925)	0.6 Units on a scale Standard Deviation 25.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 3/Day 1) (n=876)	-0.4 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 4/Day 1) (n=833)	-1.7 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 5/Day 1) (n=807)	-1.2 Units on a scale Standard Deviation 26.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 6/Day 1) (n=775)	-1.4 Units on a scale Standard Deviation 26.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 7/Day 1) (n=737)	-2.6 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 8/Day 1) (n=703)	-2.1 Units on a scale Standard Deviation 25.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 9/Day 1) (n=668)	-1.8 Units on a scale Standard Deviation 27.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 10/Day 1) (n=635)	-1.0 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 11/Day 1) (n=575)	-1.6 Units on a scale Standard Deviation 27.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 12/Day 1) (n=413)	-0.8 Units on a scale Standard Deviation 27.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 13/Day 1) (n=512)	-1.5 Units on a scale Standard Deviation 27.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 14/Day 1) (n=354)	-2.1 Units on a scale Standard Deviation 28.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 15/Day 1) (n=462)	-0.7 Units on a scale Standard Deviation 27.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 16/Day 1) (n=294)	-1.5 Units on a scale Standard Deviation 29.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 17/Day 1) (n=418)	-0.3 Units on a scale Standard Deviation 28.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 18/Day 1) (n=249)	-0.7 Units on a scale Standard Deviation 28.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 19/Day 1) (n=378)	-1.5 Units on a scale Standard Deviation 23.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 20/Day 1) (n=221)	-0.0 Units on a scale Standard Deviation 28.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 21/Day 1) (n=342)	0.2 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 22/Day 1) (n=182)	-3.7 Units on a scale Standard Deviation 27.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 23/Day 1) (n=310)	-1.0 Units on a scale Standard Deviation 26.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 24/Day 1) (n=156)	-1.7 Units on a scale Standard Deviation 26.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 25/Day 1) (n=295)	2.3 Units on a scale Standard Deviation 25.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 28/Day 1) (n=119)	-0.6 Units on a scale Standard Deviation 27.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 29/Day 1) (n=249)	1.5 Units on a scale Standard Deviation 26.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 30/Day 1) (n=107)	-0.6 Units on a scale Standard Deviation 28.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (End of treatment) (n=451)	-0.6 Units on a scale Standard Deviation 26.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 2/Day 1) (n=928)	1.0 Units on a scale Standard Deviation 20.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 3/Day 1) (n=879)	-0.2 Units on a scale Standard Deviation 19.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 4/Day 1) (n=834)	-0.6 Units on a scale Standard Deviation 19.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 5/Day 1) (n=808)	-1.3 Units on a scale Standard Deviation 17.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 6/Day 1) (n=776)	-1.8 Units on a scale Standard Deviation 17.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 7/Day 1) (n=738)	-1.2 Units on a scale Standard Deviation 18.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 8/Day 1) (n=704)	-2.2 Units on a scale Standard Deviation 17.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 9/Day 1) (n=669)	-2.1 Units on a scale Standard Deviation 18.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 10/Day 1) (n=636)	-1.7 Units on a scale Standard Deviation 19.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 11/Day 1) (n=577)	-1.8 Units on a scale Standard Deviation 17.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 12/Day 1) (n=414)	-1.9 Units on a scale Standard Deviation 17.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 13/Day 1) (n=514)	-1.5 Units on a scale Standard Deviation 18.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 14/Day 1) (n=354)	-1.3 Units on a scale Standard Deviation 14.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 15/Day 1) (n=463)	-0.9 Units on a scale Standard Deviation 16.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 16/Day 1) (n=294)	0.1 Units on a scale Standard Deviation 16.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 17/Day 1) (n=422)	-1.4 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 18/Day 1) (n=249)	-0.9 Units on a scale Standard Deviation 18.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 19/Day 1) (n=379)	-0.9 Units on a scale Standard Deviation 17.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 20/Day 1) (n=223)	-1.3 Units on a scale Standard Deviation 17.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 21/Day 1) (n=344)	-0.6 Units on a scale Standard Deviation 18.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 22/Day 1) (n=182)	-1.1 Units on a scale Standard Deviation 14.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 23/Day 1) (n=311)	0.3 Units on a scale Standard Deviation 17.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 24/Day 1) (n=156)	2.6 Units on a scale Standard Deviation 17.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 25/Day 1) (n=294)	-1.6 Units on a scale Standard Deviation 17.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 26/Day 1) (n=126)	-2.4 Units on a scale Standard Deviation 14.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 27/Day 1) (n=274)	-0.6 Units on a scale Standard Deviation 18.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 28/Day 1) (n=120)	-0.3 Units on a scale Standard Deviation 15.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 29/Day 1) (n=249)	-1.7 Units on a scale Standard Deviation 16.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (Cycle 30/Day 1) (n=107)	-1.2 Units on a scale Standard Deviation 12.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Sore Mouth (End of treatment) (n=451)	-0.4 Units on a scale Standard Deviation 20.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 20/Day 1) (n=222)	-9.0 Units on a scale Standard Deviation 30.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 24/Day 1) (n=156)	-4.1 Units on a scale Standard Deviation 34.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 29/Day 1) (n=247)	-9.2 Units on a scale Standard Deviation 28.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Alopecia (Cycle 30/Day 1) (n=107)	-5.0 Units on a scale Standard Deviation 31.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 6/Day 1) (n=775)	-18.3 Units on a scale Standard Deviation 32.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 13/Day 1) (n=513)	-18.6 Units on a scale Standard Deviation 32.6	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 28/Day 1) (n=119)	-19.6 Units on a scale Standard Deviation 30.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 29/Day 1) (n=249)	-17.1 Units on a scale Standard Deviation 31.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Coughing (Cycle 30/Day 1) (n=106)	-16.7 Units on a scale Standard Deviation 29.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 3/Day 1) (n=879)	-1.1 Units on a scale Standard Deviation 20.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 6/Day 1) (n=776)	-3.0 Units on a scale Standard Deviation 19.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 10/Day 1) (n=637)	-2.9 Units on a scale Standard Deviation 19.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 15/Day 1) (n=463)	-2.8 Units on a scale Standard Deviation 17.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 20/Day 1) (n=223)	-3.4 Units on a scale Standard Deviation 18.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 23/Day 1) (n=311)	-3.4 Units on a scale Standard Deviation 17.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dysphagia (Cycle 27/Day 1) (n=274)	-1.6 Units on a scale Standard Deviation 17.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Dyspnoea (Cycle 28/Day 1) (n=120)	-5.8 Units on a scale Standard Deviation 19.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 13/Day 1) (n=514)	-2.1 Units on a scale Standard Deviation 12.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Haemoptysis (Cycle 15/Day 1) (n=462)	-2.2 Units on a scale Standard Deviation 10.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 16/Day 1) (n=293)	-9.9 Units on a scale Standard Deviation 28.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 22/Day 1) (n=182)	-9.0 Units on a scale Standard Deviation 29.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Arm or Shoulder (Cycle 23/Day 1) (n=311)	-8.9 Units on a scale Standard Deviation 25.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 7/Day 1) (n=735)	-12.6 Units on a scale Standard Deviation 25.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 13/Day 1) (n=513)	-12.6 Units on a scale Standard Deviation 24.5	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 15/Day 1) (n=462)	-11.9 Units on a scale Standard Deviation 24.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 18/Day 1) (n=249)	-8.0 Units on a scale Standard Deviation 23.1	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 19/Day 1) (n=378)	-11.2 Units on a scale Standard Deviation 23.8	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 20/Day 1) (n=222)	-9.4 Units on a scale Standard Deviation 24.3	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 26/Day 1) (n=126)	-10.6 Units on a scale Standard Deviation 25.2	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 27/Day 1) (n=272)	-9.2 Units on a scale Standard Deviation 22.0	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 28/Day 1) (n=120)	-9.4 Units on a scale Standard Deviation 26.7	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Chest (Cycle 29/Day 1) (n=248)	-9.5 Units on a scale Standard Deviation 24.4	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Pain in Other Parts (Cycle 3/Day 1) (n=854)	-12.0 Units on a scale Standard Deviation 31.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 26/Day 1) (n=126)	-1.6 Units on a scale Standard Deviation 24.9	—
Mean Change From Baseline of QLQ-LC13 Scale Scores Peripheral Neuropathy (Cycle 27/Day 1) (n=274)	2.1 Units on a scale Standard Deviation 27.1	—

SECONDARY outcome

Timeframe: 6 years

Population: The safety analysis population included all participants who were enrolled and received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing).

The participants who responded to the question: "Have you experienced any visual disturbances?" Only the participants who answered yes were instructed to complete the rest of the questionnaire. N was the number of participants who had completed the first question.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=1066 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 2/Day 1 (Yes) (N=798)	64.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 2/Day 1 (No) (N=798)	35.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 3/Day 1 (Yes) (N=768)	56.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 3/Day 1 (No) (N=768)	43.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 4/Day 1 (Yes) (N=754)	52.3 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 4/Day 1 (No) (N=754)	47.7 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 5/Day 1 (Yes) (N=743)	49.1 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 5/Day 1 (No) (N=743)	50.9 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 6/Day 1 (Yes) (N=731)	48.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 6/Day 1 (No) (N=731)	51.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 7/Day 1 (Yes) (N=699)	45.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 7/Day 1 (No) (N=699)	54.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 8/Day 1 (Yes) (N=670)	43.7 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 8/Day 1 (No) (N=670)	56.3 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 9/Day 1 (Yes) (N=653)	43.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 9/Day 1 (No) (N=653)	56.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 10/Day 1 (Yes) (N=621)	42.7 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 10/Day 1 (No) (N=621)	57.3 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 11/Day 1 (Yes) (N=565)	40.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 11/Day 1 (No) (N=565)	59.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 12/Day 1 (Yes) (N=403)	42.9 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 12/Day 1 (No) (N=403)	57.1 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 13/Day 1 (Yes) (N=507)	41.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 13/Day 1 (No) (N=507)	58.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 14/Day 1 (Yes) (N=354)	41.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 14/Day 1 (No) (N=354)	58.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 15/Day 1 (Yes) (N=468)	39.1 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 15/Day 1 (No) (N=468)	60.9 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 16/Day 1 (Yes) (N=296)	43.6 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 16/Day 1 (No) (N=296)	56.4 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 17/Day 1 (Yes) (N=418)	37.3 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 17/Day 1 (No) (N=418)	62.7 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 18/Day 1 (Yes) (N=249)	40.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 18/Day 1 (No) (N=249)	59.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 19/Day 1 (Yes) (N=378)	36.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 19/Day 1 (No) (N=378)	63.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 20/Day 1 (Yes) (N=221)	38.9 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 20/Day 1 (No) (N=221)	61.1 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 21/Day 1 (Yes) (N=344)	39.0 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 21/Day 1 (No) (N=344)	61.0 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 22/Day 1 (Yes) (N=181)	39.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 22/Day 1 (No) (N=181)	60.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 23/Day 1 (Yes) (N=312)	34.9 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 23/Day 1 (No) (N=312)	65.1 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 24/Day 1 (Yes) (N=155)	34.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 24/Day 1 (No) (N=155)	65.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 25/Day 1 (Yes) (N=302)	35.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 25/Day 1 (No) (N=302)	64.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 26/Day 1 (Yes) (N=130)	30.8 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 26/Day 1 (No) (N=130)	69.2 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 27/Day 1 (Yes) (N=276)	32.6 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 27/Day 1 (No) (N=276)	67.4 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 28/Day 1 (Yes) (N=118)	31.4 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 28/Day 1 (No) (N=118)	68.6 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 29/Day 1 (Yes) (N=249)	30.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 29/Day 1 (No) (N=249)	69.5 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 30/Day 1 (Yes) (N=106)	27.4 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) Cycle 30/Day 1 (No) (N=106)	72.6 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) End of Treatment (Yes) (N=428)	39.3 Percentage of participants	—
Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK) End of Treatment (No) (N=428)	60.7 Percentage of participants	—

SECONDARY outcome

Timeframe: 6 years

Population: The PRO evaluable population was defined as the participants from the SA population who completed a baseline assessment and at least one post-baseline assessment.

The EQ-5D descriptive system measured a patient's health state on 5 dimensions which included: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS. n is the number of participants who completed the scale at baseline and at the respective Cycle.

Outcome measures

Outcome measures
Measure	Crizotinib 250 mg BID n=974 Participants Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.	PF-06260182 PF-06260182 was a PF-02341066 metabolite measured in this study.
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 2/DAY 1 (n=926)	5.72 Units on a scale Standard Deviation 17.51	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 3/DAY 1 (n=875)	8.57 Units on a scale Standard Deviation 18.82	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 4/DAY 1 (n=836)	10.01 Units on a scale Standard Deviation 19.73	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 5/DAY 1 (n=804)	10.38 Units on a scale Standard Deviation 19.85	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 6/DAY 1 (n=771)	10.17 Units on a scale Standard Deviation 20.38	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 7/DAY 1 (n=728)	10.17 Units on a scale Standard Deviation 20.38	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 8/DAY 1 (n=693)	10.35 Units on a scale Standard Deviation 19.22	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 9/DAY 1 (n=667)	10.69 Units on a scale Standard Deviation 19.82	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 10/DAY 1 (n=633)	10.34 Units on a scale Standard Deviation 19.15	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 11/DAY 1 (n=573)	10.09 Units on a scale Standard Deviation 19.72	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 12/DAY 1 (n=409)	9.69 Units on a scale Standard Deviation 18.81	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 13/DAY 1 (n=512)	9.74 Units on a scale Standard Deviation 19.64	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 14/DAY 1 (n=351)	10.93 Units on a scale Standard Deviation 18.67	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 15/DAY 1 (n=461)	8.71 Units on a scale Standard Deviation 20.53	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 16/DAY 1 (n=289)	8.47 Units on a scale Standard Deviation 20.66	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 17/DAY 1 (n=417)	7.99 Units on a scale Standard Deviation 20.80	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 18/DAY 1 (n=244)	7.62 Units on a scale Standard Deviation 19.86	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 19/DAY 1 (n=372)	8.17 Units on a scale Standard Deviation 18.92	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 20/DAY 1 (n=219)	8.03 Units on a scale Standard Deviation 18.45	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 21/DAY 1 (n=339)	6.96 Units on a scale Standard Deviation 18.71	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 22/DAY 1 (n=179)	6.59 Units on a scale Standard Deviation 18.97	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 23/DAY 1 (n=310)	5.53 Units on a scale Standard Deviation 19.50	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 24/DAY 1 (n=154)	7.61 Units on a scale Standard Deviation 19.58	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 25/DAY 1 (n=299)	4.97 Units on a scale Standard Deviation 17.98	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 26/DAY 1 (n=128)	8.54 Units on a scale Standard Deviation 18.97	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 27/DAY 1 (n=272)	5.24 Units on a scale Standard Deviation 17.61	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 28/DAY 1 (n=120)	7.93 Units on a scale Standard Deviation 19.53	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 29/DAY 1 (n=249)	5.05 Units on a scale Standard Deviation 17.07	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale CYCLE 30/DAY 1 (n=108)	8.07 Units on a scale Standard Deviation 19.95	—
Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale End of Treatment (n=450)	0.09 Units on a scale Standard Deviation 23.92	—

Adverse Events

Crizotinib 250 mg BID

Serious events: 539 serious events

Other events: 1038 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Crizotinib 250 mg BID n=1066 participants at risk Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.
Blood and lymphatic system disorders Anaemia	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Basophilia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Eosinophilia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Febrile neutropenia	0.56% 6/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Leukocytosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Monocytosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Thrombocytopenia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Thrombocytosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Acute myocardial infarction	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Angina pectoris	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Atrial fibrillation	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Bradycardia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Cardiac arrest	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Cardiac failure	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Cardiac failure congestive	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Cardiac tamponade	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Coronary artery stenosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Cyanosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Left ventricular failure	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Myocardial infarction	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Myocarditis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Palpitations	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Pericardial effusion	0.66% 7/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Pericarditis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Supraventricular tachycardia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Syncope	0.56% 6/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Tachycardia	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Cataract	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Glaucoma	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Optic atrophy	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Retinal detachment	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Vision blurred	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Vitreous haemorrhage	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Abdominal pain	0.56% 6/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Abdominal wall haematoma	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Ascites	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Colitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Constipation	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Diarrhoea	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Diarrhoea haemorrhagic	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Dysphagia	0.66% 7/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Gastric ulcer	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Gastritis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Gastrointestinal haemorrhage	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Ileus	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Intestinal obstruction	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Intestinal perforation	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Nausea	0.84% 9/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Oesophageal stenosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Oesophagitis	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Pancreatic atrophy	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Pancreatitis	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Pancreatitis acute	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Peptic ulcer haemorrhage	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Peritoneal disorder	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Retroperitoneal haemorrhage	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Small intestinal obstruction	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Subileus	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Vomiting	0.56% 6/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Asthenia	0.66% 7/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Chest discomfort	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Chest pain	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Chills	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Condition aggravated	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Death	0.75% 8/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Device dislocation	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Disease progression	12.7% 135/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Fatigue	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Gait disturbance	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders General physical health deterioration	0.84% 9/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Generalised oedema	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Mass	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Multi-organ failure	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Oedema peripheral	0.66% 7/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Pain	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Pyrexia	1.7% 18/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Hepatobiliary disorders Cholecystitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Hepatobiliary disorders Drug-induced liver injury	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Hepatobiliary disorders Hepatic failure	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Hepatobiliary disorders Hepatitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Hepatobiliary disorders Hepatocellular injury	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Hepatobiliary disorders Hepatotoxicity	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Immune system disorders Contrast media allergy	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Abdominal abscess	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Abscess limb	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Appendicitis	0.75% 8/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Bacteraemia	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Bone abscess	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Bronchitis	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Candiduria	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Cellulitis	1.2% 13/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Chest wall abscess	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Clostridium difficile infection	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Cystitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Diverticulitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Empyema	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Gastroenteritis	0.56% 6/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Herpes zoster	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Infection	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Infectious pleural effusion	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Infective spondylitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Lower respiratory tract infection	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Lung abscess	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Lung infection	1.3% 14/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Meningitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Metapneumovirus infection	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Oesophageal candidiasis	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Osteomyelitis chronic	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Peritonitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Pneumonia	6.9% 74/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Pneumonia bacterial	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Pneumonia fungal	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Pneumonia staphylococcal	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Pyelonephritis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Renal abscess	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Renal cyst infection	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Respiratory tract infection	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Sepsis	0.75% 8/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Septic shock	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Skin infection	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Soft tissue infection	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Staphylococcal sepsis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Upper respiratory tract infection	0.66% 7/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Urinary tract infection	0.66% 7/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Urinary tract infection bacterial	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Viral infection	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Viral upper respiratory tract infection	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Wound infection	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Ankle fracture	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Bone fissure	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Dislocation of vertebra	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Fall	0.56% 6/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Femoral neck fracture	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Femur fracture	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Hip fracture	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Humerus fracture	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Joint dislocation	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Lower limb fracture	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Overdose	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Pelvic fracture	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Radiation necrosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Radiation pneumonitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Radius fracture	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Road traffic accident	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Spinal compression fracture	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Subdural haemorrhage	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Traumatic haematoma	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Upper limb fracture	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Alanine aminotransferase increased	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Blood albumin decreased	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Blood bilirubin increased	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Blood creatinine increased	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Blood lactate dehydrogenase increased	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations C-reactive protein increased	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Electrocardiogram QT prolonged	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Hepatic enzyme increased	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Troponin I increased	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Decreased appetite	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Dehydration	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Failure to thrive	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Fluid retention	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypercalcaemia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hyperglycaemia	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hyperkalaemia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypoalbuminaemia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypocalcaemia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypoglycaemia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypokalaemia	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypomagnesaemia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hyponatraemia	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypophosphataemia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Arthralgia	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Back pain	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Bursitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Chest wall mass	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Joint swelling	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Muscular weakness	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Myalgia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Myopathy	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Neck pain	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Osteoarthritis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Pain in extremity	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Pathological fracture	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Aphasia	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Ataxia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Brain oedema	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Cerebellar infarction	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Cerebral haemorrhage	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Cerebral infarction	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Cerebrovascular accident	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Chorea	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Coma	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Depressed level of consciousness	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Dizziness	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Dysarthria	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Generalised tonic-clonic seizure	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Haemorrhage intracranial	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Headache	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Intracranial pressure increased	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Ischaemic stroke	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Nervous system disorder	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Neurological decompensation	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Paraplegia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Peripheral motor neuropathy	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Peripheral sensorimotor neuropathy	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Peripheral sensory neuropathy	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Pyramidal tract syndrome	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Seizure	0.84% 9/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Spinal cord compression	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Transient ischaemic attack	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Tremor	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Vocal cord paralysis	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Completed suicide	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Confusional state	0.66% 7/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Depression	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Disorientation	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Mania	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Mental status changes	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Suicide attempt	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Acute kidney injury	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Dysuria	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Haematuria	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Hydronephrosis	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Nephrolithiasis	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Renal cyst	1.2% 13/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Renal cyst haemorrhage	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Renal failure	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Ureteral polyp	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Urinary retention	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Renal and urinary disorders Urinary tract obstruction	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Reproductive system and breast disorders Benign prostatic hyperplasia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Reproductive system and breast disorders Pelvic pain	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Alveolitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Asphyxia	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Atelectasis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Cough	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 39/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Epistaxis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Hypoxia	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.3% 14/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.6% 17/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.75% 8/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.4% 26/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Pulmonary thrombosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Rales	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.6% 17/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Skin and subcutaneous tissue disorders Paraneoplastic pemphigus	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Skin and subcutaneous tissue disorders Rash	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Surgical and medical procedures Pleural decortication	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Deep vein thrombosis	1.3% 14/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Embolism	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Haematoma	0.28% 3/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Hypotension	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Hypovolaemic shock	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Orthostatic hypotension	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Peripheral arterial occlusive disease	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Peripheral embolism	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Phlebitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Superior vena cava syndrome	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Thrombophlebitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Thrombosis	0.47% 5/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Vasculitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Vena cava thrombosis	0.19% 2/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Vascular disorders Venous thrombosis	0.38% 4/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Angina Unstable	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Rectal haemorrhage	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Vascular stent thrombosis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Lymphangitis	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Craniocerebral injury	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Postoperative wound complication	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Wound dehiscence	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Haemothorax	0.09% 1/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs

Other adverse events

Other adverse events
Measure	Crizotinib 250 mg BID n=1066 participants at risk Participants were administered crizotinib at a starting dose of 250 mg orally, BID on a continuous dosing period as two 100-mg tablets and one 50-mg tablet at approximately 12 hours apart the same time each day.
Blood and lymphatic system disorders Anaemia	12.9% 138/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Leukopenia	9.5% 101/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Lymphopenia	6.7% 71/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Blood and lymphatic system disorders Neutropenia	16.9% 180/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Cardiac disorders Bradycardia	9.2% 93/1006 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Photopsia	9.0% 96/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Vision blurred	7.5% 80/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Eye disorders Visual impairment	43.2% 460/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Abdominal pain	11.1% 118/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Abdominal pain upper	9.9% 106/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Constipation	44.6% 475/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Diarrhoea	51.4% 548/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Dyspepsia	7.6% 81/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Dysphagia	5.3% 56/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Nausea	56.6% 603/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Gastrointestinal disorders Vomiting	53.0% 565/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Asthenia	14.6% 156/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Chest pain	9.8% 105/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Fatigue	30.6% 326/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Oedema	9.0% 96/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Oedema peripheral	42.2% 450/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
General disorders Pyrexia	17.0% 181/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Nasopharyngitis	10.6% 113/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Upper respiratory tract infection	13.6% 145/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Infections and infestations Urinary tract infection	5.8% 62/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Injury, poisoning and procedural complications Fall	5.5% 59/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Alanine aminotransferase increased	30.0% 302/1006 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Aspartate aminotransferase increased	23.2% 233/1006 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Blood alkaline phosphatase increased	7.6% 76/1006 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Blood creatinine increased	10.4% 105/1006 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Blood lactate dehydrogenase increased	6.0% 60/1006 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Neutrophil count decreased	7.9% 84/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Weight decreased	10.2% 109/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations Weight increased	9.2% 98/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Investigations White blood cell count decreased	9.7% 98/1006 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Decreased appetite	30.6% 326/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hyperglycaemia	5.2% 55/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypoalbuminaemia	9.2% 98/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypocalcaemia	9.3% 99/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hypokalaemia	7.2% 77/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Arthralgia	12.3% 131/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Back pain	17.3% 184/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Muscle spasms	7.4% 79/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Muscular weakness	5.3% 57/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Pain in extremity	12.9% 137/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.9% 74/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Dizziness	24.9% 265/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Dysgeusia	20.0% 213/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Headache	20.1% 214/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Hypoaesthesia	6.1% 65/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Nervous system disorders Paraesthesia	7.8% 83/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Anxiety	7.1% 76/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Psychiatric disorders Insomnia	12.8% 136/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Cough	24.4% 260/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Dyspnoea	21.0% 224/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.2% 55/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.0% 75/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Respiratory, thoracic and mediastinal disorders Productive cough	6.7% 71/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Skin and subcutaneous tissue disorders Alopecia	6.3% 67/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Skin and subcutaneous tissue disorders Pruritus	7.9% 84/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Skin and subcutaneous tissue disorders Rash	12.6% 134/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs
Metabolism and nutrition disorders Hyponatraemia	5.1% 54/1066 • Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter. All causality (serious and non-serious) AEs

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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