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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

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ClinicalTrials.gov Identifier: NCT00932451
Recruitment Status : Completed
First Posted : July 3, 2009
Results First Posted : June 9, 2016
Last Update Posted : January 13, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Intervention Drug: PF-02341066
Enrollment 1069
Recruitment Details A total of 1069 participants entered the study out of which 3 participants were withdrawn from the study before receiving study treatment because they were not eligible and were mistakenly entered into the interactive voice response system.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.
Pre-assignment Details 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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 1066
Completed 244
Not Completed 822
Reason Not Completed
Withdrawal by Subject             69
Lost to Follow-up             22
Death             726
Other reasons             5
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description 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 Number of Baseline Participants 1066
Hide Baseline Analysis Population Description
An Investigational Use Only (IUO) population (N=908) was all participants whose non-small cell lung cancer (NSCLC) was Fluorescent In-Situ Hybridization (FISH) ALK (Anaplastic Lymphoma Receptor Tyrosine Kinase) (+) by the central laboratory. A non-IUO population (N=158) was all partcipants whose NSCLC was ALK (+) by local assay testing.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1066 participants
52.2  (12.33)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 1066 participants
< 65 years 894
>=65 years 172
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1066 participants
Female
601
  56.4%
Male
465
  43.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 1066 participants
Chinese 252
Japanese 81
Korean 144
White 532
Black 20
Other 19
Other-Asian 18
1.Primary Outcome
Title Objective Response Rate
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
ALK Positive by IUO; N=908
54.1
(50.8 to 57.4)
ALK Positive by non-IUO only, N= 158
40.5
(32.8 to 48.6)
2.Primary Outcome
Title Percentage of Participants With Adverse Events
Hide Description 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).
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Measure Type: Number
Unit of Measure: Percentage of Participants
Serious AEs (all causalities) 50.6
Grade 3/4 AEs (all causalities) 65.6
Grade 5 AEs (all causalities) 22.7
Serious AEs (treatment related) 11.5
Grade 3/4 AEs (treatment related) 40.2
Grade 5 AEs (treatment related) 1.6
3.Secondary Outcome
Title Duration of Response (DR)
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Median (95% Confidence Interval)
Unit of Measure: Months
ALK Positive by IUO, N=491
11.8
(10.4 to 12.8)
ALK Positive by non-IUO only, N=64
9.5
(6.9 to 15.2)
4.Secondary Outcome
Title Time to Tumor Response (TTR)
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Median (Full Range)
Unit of Measure: Weeks
ALK Positive by IUO (n=491)
6.1
(2.7 to 164)
ALK Positive by non-IUO only (n=64)
6.3
(4.7 to 65.9)
5.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
ALK Positive by IUO at Week 6, N=908
81.7
(79.0 to 84.2)
ALK Positive by IUO at Week 12, N=908
70.8
(67.7 to 73.8)
ALK Positive by non-IUO at Week 6, N=158
69.6
(61.8 to 76.7)
ALK Positive by non-IUO at Week 12, N=158
61.4
(53.3 to 69.0)
6.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Median (95% Confidence Interval)
Unit of Measure: Months
ALK Positive by IUO , N= 908
8.4
(7.1 to 9.7)
ALK Positive by non-IUO only , N=158
6.9
(5.6 to 9.4)
7.Secondary Outcome
Title Overall Survival (OS)
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Median (95% Confidence Interval)
Unit of Measure: Months
ALK-positive by IUO (N= 908)
21.8
(19.4 to 24.0)
ALK-positive by non-IUO (N= 158)
16.9
(13.4 to 21.5)
8.Secondary Outcome
Title Probability of Survival
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of probability
ALK positive by IUO at 6 Months
81.7
(79.0 to 84.0)
ALK positive by non IUO at 6 Months
77.5
(70.1 to 83.3)
ALK positive by IUO at 12 Months
66.5
(63.3 to 69.5)
ALK positive by non IUO at 12 Months
62.4
(54.3 to 69.6)
9.Secondary Outcome
Title Plasma Concentrations of Crizotinib (PF-02341066) and Its Metabolite PF-06260182
Hide Description Plasma concentrations of crizotinib (PF-02341066) and its metabolite PF-06260182. The method of dispersion is % coefficient of variation.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib (PF-02341066) PF-06260182
Hide Arm/Group Description:
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 was a PF-02341066 metabolite measured in this study.
Overall Number of Participants Analyzed 906 904
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Day 1 (N= 13, 13)
1.95
(55%)
0.00601
(167%)
Cycle 2 Day 1 (N=447, 431)
279
(46%)
76.2
(79%)
Cycle 3 Day 1 (N=398, 385)
297
(44%)
80.8
(58%)
Cycle 5 Day 1 (N=297, 290)
294
(48%)
81.4
(61%)
10.Secondary Outcome
Title Molecular Profiling (ALK Status) Descriptive Statistics for ALK Percentage of Positive Cells by Central Laboratory Test (SA [ALK Positive by IUO] Population)
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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)
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 908
Median (Full Range)
Unit of Measure: Percentage of cells
60.0
(15.0 to 100.0)
11.Secondary Outcome
Title Genotypes of Alleles Possibly Associated With Adverse Hepatic Drug Reactions (Pharmacogenomic Evaluable Population)
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID-ALT Cases Crizotinib 250 mg BID-ALT Controls
Hide Arm/Group Description:
Participants were administered crizotinib at a starting dose of 250 milligram [mg] orally, twice daily (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.
Participants were administered crizotinib at a starting dose of 250 milligram [mg] orally, twice daily (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 Number of Participants Analyzed 74 115
Measure Type: Number
Unit of Measure: Percentage of participants
HLA-DQA1*02:01 20.3 20.0
HLA-DQB1*02:02 17.6 16.5
HLA-DRB1*07:01 20.3 20.0
TNXB/rs12153855 10.8 16.5
HLA-B*57:01 2.7 4.3
HLA-DRB1*15:01 17.6 20.9
12.Secondary Outcome
Title QTc Prolongation in Participants
Hide Description The percentage of participants with maximum post-dose QTcF/QTcB (<450, 450 - <480, 480 - <500, and ≥500 msec) were evaluated.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 999
Measure Type: Number
Unit of Measure: Percentage of participants
Maximum QTcF Interval (<450) 89.8
Maximum QTcF Interval (450-<480) 7.7
Maximum QTcF Interval (480 - <500) 1.0
Maximum QTcF Interval (≥500) 1.5
Maximum QTcB Interval (<450) 74.3
Maximum QTcB Interval (450-<480) 21.2
Maximum QTcB Interval (480-<500) 2.4
Maximum QTcB Interval (≥500) 2.1
13.Secondary Outcome
Title Mean Change From Baseline in QLQ-C30 Global Quality of Life Scores.
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 976
Mean (Standard Deviation)
Unit of Measure: Units on a scale
CYCLE2/DAY1 (n=929) 7.9  (22.2)
CYCLE3/DAY1 (n=872) 10.6  (23.7)
CYCLE4/DAY1 (n=828) 12.2  (24.9)
CYCLE5/DAY1 (n=806) 11.5  (23.9)
CYCLE6/DAY1 (n=774) 11.9  (24.8)
CYCLE7/DAY1 (n=734) 12.3  (24.7)
CYCLE8/DAY1 (n=699) 12.3  (24.1)
CYCLE9/DAY1 (n=665) 11.8  (23.5)
CYCLE10/DAY1 (n=631) 11.5  (23.6)
CYCLE11/DAY1 (n=570) 10.4  (23.9)
CYCLE12/DAY1 (n=411) 10.1  (21.6)
CYCLE13/DAY1 (n=512) 11.0  (24.0)
CYCLE14/DAY1 (n=353) 10.4  (21.5)
CYCLE15/DAY1 (n=462) 9.5  (23.9)
CYCLE16/DAY1 (n=294) 7.4  (23.2)
CYCLE17/DAY1 (n=419) 8.0  (24.3)
CYCLE18/DAY1 (n=247) 7.8  (22.0)
CYCLE19/DAY1 (n=376) 7.8  (23.1)
CYCLE20/DAY1 (n=222) 9.1  (22.4)
CYCLE21/DAY1 (n=340) 7.8  (22.5)
CYCLE22/DAY1 (n=179) 5.9  (23.7)
CYCLE23/DAY1 (n=305) 6.7  (24.0)
CYCLE24/DAY1 (n=154) 6.4  (25.0)
CYCLE25/DAY1 (n=293) 4.7  (23.3)
CYCLE26/DAY1 (n=127) 8.3  (24.7)
CYCLE27/DAY1 (n=269) 5.9  (23.2)
CYCLE28/DAY1 (n=120) 6.7  (24.2)
CYCLE29/DAY1 (n=247) 5.7  (23.3)
CYCLE30/DAY1 (n=105) 6.4  (24.9)
End of treatment (n=450) -1.0  (27.2)
14.Secondary Outcome
Title Mean Change From Baseline of EORTC QLQ-C30 Functional and Symptom Scale Scores
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 976
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Physical Functioning (Cycle 2/Day 1) (n=936) 4.3  (17.1)
Physical Functioning (Cycle 3/Day 1) (n=879) 6.6  (18.6)
Physical Functioning (Cycle 4/Day 1) (n=836) 8.2  (19.1)
Physical Functioning (Cycle 5/Day 1) (n=810) 8.8  (18.8)
Physical Functioning (Cycle 6/Day 1) (n=778) 9.5  (18.6)
Physical Functioning (Cycle 7/Day 1) (n=739) 10.0  (19.3)
Physical Functioning (Cycle 8/Day 1) (n= 704) 10.1  (18.8)
Physical Functioning (Cycle 9/Day 1) (n= 673) 10.5  (18.2)
Physical Functioning (Cycle 10/Day 1) (n= 637) 9.5  (17.9)
Physical Functioning (Cycle 11/Day 1) (n=577) 9.1  (17.9)
Physical Functioning (Cycle 12/Day 1) (n=412) 8.2  (17.3)
Physical Functioning (Cycle 13/Day 1) (n=517) 8.7  (18.1)
Physical Functioning (Cycle 14/Day 1) (n=358) 8.2  (16.5)
Physical Functioning (Cycle 15/Day 1) (n=466) 7.3  (19.2)
Physical Functioning (Cycle 16/Day 1) (n=295) 6.3  (19.1)
Physical Functioning (Cycle 17/Day 1) (n=424) 6.0  (18.9)
Physical Functioning (Cycle 18/Day 1) (n=250) 6.1  (18.4)
Physical Functioning (Cycle 19/Day 1) (n=380) 6.6  (16.8)
Physical Functioning (Cycle 20/Day 1) (n=224) 5.1  (16.8)
Physical Functioning (Cycle 21/Day 1) (n=346) 5.7  (17.6)
Physical Functioning (Cycle 22/Day 1) (n=182) 3.8  (17.0)
Physical Functioning (Cycle 23/Day 1) (n=311) 3.7  (17.1)
Physical Functioning (Cycle 24/Day 1) (n=156) 2.4  (18.9)
Physical Functioning (Cycle 25/Day 1) (n=296) 4.0  (18.0)
Physical Functioning (Cycle 26/Day 1) (n=129) 5.3  (18.1)
Physical Functioning (Cycle 27/Day 1) (n=275) 3.8  (16.1)
Physical Functioning (Cycle 28/Day 1) (n=121) 3.6  (20.4)
Physical Functioning (Cycle 29/Day 1) (n=251) 3.7  (15.8)
Physical Functioning (Cycle 30/Day 1) (n=109) 2.8  (21.9)
Physical Functioning (End of treatment) (n=451) 0.1  (25.0)
Cognitive functioning (Cycle 2/Day 1) (n=930) 1.0  (18.4)
Cognitive Functioning (Cycle 3/Day 1) (n=874) 2.1  (19.4)
Cognitive Functioning (Cycle 4/Day 1) (n=829) 2.1  (18.6)
Cognitive Functioning (Cycle 5/Day 1) (n=806) 2.3  (18.4)
Cognitive Functioning (Cycle 6/Day 1) (n=773) 2.5  (18.2)
Cognitive Functioning (Cycle 7/Day 1) (n=734) 3.2  (18.6)
Cognitive Functioning (Cycle 8/Day 1) (n=699) 3.3  (18.5)
Cognitive Functioning (Cycle 9/Day 1) (n=667) 3.0  (18.4)
Cognitive Functioning (Cycle 10/Day 1) (n=632) 2.7  (19.0)
Cognitive Functioning (Cycle 11/Day 1) (n=571) 3.0  (18.5)
Cognitive Functioning (Cycle 12/Day 1) (n=411) 1.5  (17.1)
Cognitive Functioning (Cycle 13/Day 1) (n=512) 2.0  (19.3)
Cognitive Functioning (Cycle 14/Day 1) (n=352) 1.2  (17.8)
Cognitive Functioning (Cycle 15/Day 1) (n=462) 1.3  (19.7)
Cognitive Functioning (Cycle 16/Day 1) (n=294) -0.1  (18.1)
Cognitive Functioning (Cycle 17/Day 1) (n=419) 0.0  (19.4)
Cognitive Functioning (Cycle 18/Day 1) (n=247) 0.1  (19.2)
Cognitive Functioning (Cycle 19/Day 1) (n=376) 0.1  (19.2)
Cognitive Functioning (Cycle 20/Day 1) (n=222) 0.9  (18.1)
Cognitive Functioning (Cycle 21/Day 1) (n=340) -0.1  (17.8)
Cognitive Functioning (Cycle 22/Day 1) (n=179) -1.1  (17.5)
Cognitive Functioning (Cycle 23/Day 1) (n=305) -0.3  (17.6)
Cognitive Functioning (Cycle 24/Day 1) (n=154) -3.6  (21.2)
Cognitive Functioning (Cycle 25/Day 1) (n=293) -1.3  (18.1)
Cognitive Functioning (Cycle 26/Day 1) (n=127) -0.3  (20.2)
Cognitive Functioning (Cycle 27/Day 1) (n=269) -0.9  (17.7)
Cognitive Functioning (Cycle 28/Day 1) (n=120) -0.6  (20.7)
Cognitive Functioning (Cycle 29/Day 1) (n=247) -0.2  (16.0)
Cognitive Functioning (Cycle 30/Day 1) (n=106) -2.5  (23.7)
Cognitive Functioning (End of treatment) (n=449) -2.3  (21.7)
Emotional Functioning (Cycle 2/Day 1) (n=928) 5.5  (18.4)
Emotional Functioning (Cycle 3/Day 1) (n=873) 6.8  (18.8)
Emotional Functioning (Cycle 4/Day 1) (n=827) 8.2  (18.3)
Emotional Functioning (Cycle 5/Day 1) (n=804) 7.8  (18.3)
Emotional Functioning (Cycle 6/Day 1) (n=772) 8.6  (18.0)
Emotional Functioning (Cycle 7/Day 1) (n=731) 8.3  (18.3)
Emotional Functioning (Cycle 8/Day 1) (n=697) 9.2  (18.9)
Emotional Functioning (Cycle 9/Day 1) (n=665) 8.7  (18.6)
Emotional Functioning (Cycle 10/Day 1) (n=630) 8.5  (18.9)
Emotional Functioning (Cycle 11/Day 1) (n=571) 8.5  (17.6)
Emotional Functioning (Cycle 12/Day 1) (n=410) 8.4  (17.6)
Emotional Functioning (Cycle 13/Day 1) (n=511) 8.5  (19.1)
Emotional Functioning (Cycle 14/Day 1) (n=352) 7.9  (16.6)
Emotional Functioning (Cycle 15/Day 1) (n=461) 8.3  (18.7)
Emotional Functioning (Cycle 16/Day 1) (n=293) 7.5  (16.8)
Emotional Functioning (Cycle 17/Day 1) (n=418) 6.9  (19.2)
Emotional Functioning (Cycle 18/Day 1) (n=246) 7.5  (17.2)
Emotional Functioning (Cycle 19/Day 1) (n=376) 7.4  (18.3)
Emotional Functioning (Cycle 20/Day 1) (n=221) 7.4  (17.6)
Emotional Functioning (Cycle 21/Day 1) (n=340) 6.7  (17.5)
Emotional Functioning (Cycle 22/Day 1) (n=178) 5.2  (17.9)
Emotional Functioning (Cycle 23/Day 1) (n=305) 6.6  (17.6)
Emotional Functioning (Cycle 24/Day 1) (n=153) 4.4  (19.5)
Emotional Functioning (Cycle 25/Day 1) (n=293) 6.2  (17.4)
Emotional Functioning (Cycle 26/Day 1) (n=126) 7.5  (18.9)
Emotional Functioning (Cycle 27/Day 1) (n=269) 6.3  (17.6)
Emotional Functioning (Cycle 28/Day 1) (n=119) 4.1  (19.2)
Emotional Functioning (Cycle 29/Day 1) (n=247) 5.9  (17.7)
Emotional Functioning (Cycle 30/Day 1) (n=105) 3.2  (21.5)
Emotional Functioning (End of treatment) (n=448) 1.9  (22.3)
Role Functioning (Cycle 2/Day 1) (n=935) 4.2  (25.0)
Role Functioning (Cycle 3/Day 1) (n=879) 7.3  (27.8)
Role Functioning (Cycle 4/Day 1) (n=835) 9.3  (28.7)
Role Functioning (Cycle 5/Day 1) (n=809) 9.5  (28.4)
Role Functioning (Cycle 6/Day 1) (n=778) 10.5  (28.7)
Role Functioning (Cycle 7/Day 1) (n=738) 10.4  (30.2)
Role Functioning (Cycle 8/Day 1) (n=702) 10.8  (28.5)
Role Functioning (Cycle 9/Day 1) (n=671) 10.9  (28.1)
Role Functioning (Cycle 10/Day 1) (n=635) 10.8  (28.8)
Role Functioning (Cycle 11/Day 1) (n=576) 10.0  (29.0)
Role Functioning (Cycle 12/Day 1) (n=413) 8.4  (28.0)
Role Functioning (Cycle 13/Day 1) (n=516) 9.0  (28.8)
Role Functioning (Cycle 14/Day 1) (n=358) 8.4  (26.5)
Role Functioning (Cycle 15/Day 1) (n=465) 8.8  (28.7)
Role Functioning (Cycle 16/Day 1) (n=296) 6.0  (28.3)
Role Functioning (Cycle 17/Day 1) (n=424) 6.1  (30.4)
Role Functioning (Cycle 18/Day 1) (n=250) 5.2  (27.8)
Role Functioning (Cycle 19/Day 1) (n=380) 8.0  (27.5)
Role Functioning (Cycle 20/Day 1) (n=224) 5.8  (25.1)
Role Functioning (Cycle 21/Day 1) (n=346) 5.3  (27.1)
Role Functioning (Cycle 22/Day 1) (n=182) 4.1  (26.7)
Role Functioning (Cycle 23/Day 1) (n=311) 3.2  (27.9)
Role Functioning (Cycle 24/Day 1) (n=157) 2.7  (29.5)
Role Functioning (Cycle 25/Day 1) (n=297) 2.2  (27.2)
Role Functioning (Cycle 26/Day 1) (n=129) 6.1  (28.0)
Role Functioning (Cycle 27/Day 1) (n=275) 2.4  (27.6)
Role Functioning (Cycle 28/Day 1) (n=121) 1.5  (30.0)
Role Functioning (Cycle 29/Day 1)(n=251) 1.6  (24.6)
Role Functioning (Cycle 30/Day 1) (n=109) 1.1  (34.0)
Role Functioning (End of treatment) (n=451) -1.6  (31.9)
Social Functioning (Cycle 2/Day 1) (n=928) 6.8  (25.9)
Social Functioning (Cycle 3/Day 1) (n=872) 9.1  (26.2)
Social Functioning (Cycle 4/Day 1) (n=828) 10.4  (27.2)
Social Functioning (Cycle 5/Day 1) (n=805) 10.6  (26.7)
Social Functioning (Cycle 6/Day 1) (n=773) 11.1  (27.0)
Social Functioning (Cycle 7/Day 1) (n=733) 12.1  (26.5)
Social Functioning (Cycle 8/Day 1) (n=698) 12.3  (26.4)
Social Functioning (Cycle 9/Day 1) (n=666) 12.0  (26.4)
Social Functioning (Cycle 10/Day 1) (n=631) 11.8  (26.1)
Social Functioning (Cycle 11/Day 1) (n=570) 12.1  (27.3)
Social Functioning (Cycle 12/Day 1) (n=410) 10.3  (26.3)
Social Functioning (Cycle 13/Day 1) (n=512) 10.6  (27.3)
Social Functioning (Cycle 14/Day 1) (n=352) 10.4  (25.1)
Social Functioning (Cycle 15/Day 1) (n=462) 10.1  (28.1)
Social Functioning (Cycle 16/Day 1) (n=293) 9.0  (26.4)
Social Functioning (Cycle 17/Day 1) (n=418) 8.8  (26.9)
Social Functioning (Cycle 18/Day 1) (n=246) 6.6  (25.4)
Social Functioning (Cycle 19/Day 1) (n=376) 8.0  (25.6)
Social Functioning (Cycle 20/Day 1) (n=221) 5.7  (23.9)
Social Functioning (Cycle 21/Day 1) (n=340) 6.7  (26.6)
Social Functioning (Cycle 22/Day 1) (n=178) 5.3  (22.7)
Social Functioning (Cycle 23/Day 1) (n=305) 7.0  (24.9)
Social Functioning (Cycle 24/Day 1) (n=153) 3.6  (26.5)
Social Functioning (Cycle 25/Day 1) (n=293) 4.4  (25.8)
Social Functioning (Cycle 26/Day 1) (n=126) 5.2  (26.6)
Social Functioning (Cycle 27/Day 1) (n=269) 5.3  (26.4)
Social Functioning (Cycle 28/Day 1) (n=119) 2.1  (31.4)
Social Functioning (Cycle 29/Day 1) (n=247) 6.6  (24.1)
Social Functioning (Cycle 30/Day 1) (n=105) 1.6  (29.0)
Social Functioning (End of treatment) (n=449) 2.7  (31.2)
Appetite loss (Cycle 2/Day 1) (n=936) -2.1  (30.3)
Appetite loss (Cycle 3/Day 1) (n=877) -6.3  (31.7)
Appetite loss (Cycle 4/Day 1) (n=833) -9.1  (31.9)
Appetite loss (Cycle 5/Day 1) (n=810) -10.4  (31.9)
Appetite loss (Cycle 6/Day 1) (n=778) -11.4  (32.1)
Appetite loss (Cycle 7/Day 1) (n=738) -11.4  (32.4)
Appetite loss (Cycle 8/Day 1) (n=704) -11.5  (32.6)
Appetite loss (Cycle 9/Day 1) (n=673) -11.7  (32.5)
Appetite loss (Cycle 10/Day 1) (n=637) -11.9  (30.9)
Appetite loss (Cycle 11/Day 1) (n=577) -11.2  (30.4)
Appetite loss (Cycle 12/Day 1) (n=413) -9.1  (30.9)
Appetite loss (Cycle 13/Day 1) (n=517) -11.3  (29.8)
Appetite loss (Cycle 14/Day 1) (n=358) -9.9  (31.8)
Appetite loss (Cycle 15/Day 1) (n=466) -10.5  (30.6)
Appetite loss (Cycle 16/Day 1) (n=296) -10.4  (32.4)
Appetite loss (Cycle 17/Day 1) (n=424) -8.6  (29.5)
Appetite loss (Cycle 18/Day 1) (n=250) -10.1  (31.5)
Appetite loss (Cycle 19/Day 1) (n=380) -8.9  (30.9)
Appetite loss (Cycle 20/Day 1) (n=224) -12.8  (29.0)
Appetite loss (Cycle 21/Day 1) (n=346) -7.5  (30.6)
Appetite loss (Cycle 22/Day 1) (n=181) -9.2  (27.7)
Appetite loss (Cycle 23/Day 1) (n=310) -4.9  (28.5)
Appetite loss (Cycle 24/Day 1) (n=157) -10.9  (30.1)
Appetite loss (Cycle 25/Day 1) (n=297) -4.6  (29.0)
Appetite loss (Cycle 26/Day 1) (n=129) -12.1  (32.3)
Appetite loss (Cycle 27/Day 1) (n=275) -4.2  (29.4)
Appetite loss (Cycle 28/Day 1) (n=121) -6.6  (34.6)
Appetite loss (Cycle 29/Day 1) (n=251) -3.2  (27.0)
Appetite loss (Cycle 30/Day 1) (n=109) -7.6  (29.3)
Appetite loss (End of treatment) (n=451) -0.0  (36.9)
Constipation (Cycle 2/Day 1) (n=929) 15.4  (32.9)
Constipation (Cycle 3/Day 1) (n=870) 10.9  (33.8)
Constipation (Cycle 4/Day 1) (n=827) 7.0  (31.0)
Constipation (Cycle 5/Day 1) (n=804) 5.5  (30.4)
Constipation (Cycle 6/Day 1) (n=771) 5.4  (30.3)
Constipation (Cycle 7/Day 1) (n=732) 4.7  (30.3)
Constipation (Cycle 8/Day 1) (n=698) 4.5  (29.8)
Constipation (Cycle 9/Day 1) (n=665) 5.0  (29.9)
Constipation (Cycle 10/Day 1) (n=631) 3.8  (30.0)
Constipation (Cycle 11/Day 1) (n=571) 5.2  (29.7)
Constipation (Cycle 12/Day 1) (n=410) 6.4  (29.6)
Constipation (Cycle 13/Day 1) (n=513) 5.2  (29.0)
Constipation (Cycle 14/Day 1) (n=349) 5.0  (28.7)
Constipation (Cycle 15/Day 1) (n=464) 6.0  (30.1)
Constipation (Cycle 16/Day 1) (n=291) 4.4  (29.9)
Constipation (Cycle 17/Day 1) (n=420) 8.3  (30.5)
Constipation (Cycle 18/Day 1) (n=246) 6.0  (30.7)
Constipation (Cycle 19/Day 1) (n=376) 7.4  (30.5)
Constipation (Cycle 20/Day 1) (n=221) 5.9  (33.2)
Constipation (Cycle 21/Day 1) (n=340) 7.7  (31.3)
Constipation (Cycle 22/Day 1) (n=178) 6.2  (31.2)
Constipation (Cycle 23/Day 1) (n=306) 9.7  (31.9)
Constipation (Cycle 24/Day 1) (n=154) 9.0  (34.2)
Constipation (Cycle 25/Day 1) (n=293) 10.9  (29.4)
Constipation (Cycle 26/Day 1) (n=126) 5.6  (32.0)
Constipation (Cycle 27/Day 1) (n=269) 8.3  (30.7)
Constipation (Cycle 28/Day 1) (n=119) 9.8  (31.1)
Constipation (Cycle 29/Day 1) (n=247) 7.8  (29.3)
Constipation (Cycle 30/Day 1) (n=105) 11.7  (31.3)
Constipation (End of treatment) (n=444) 8.9  (33.0)
Diarrhea (Cycle 2/Day 1) (n=927) 11.4  (25.9)
Diarrhea (Cycle 3/Day 1) (n=872) 12.8  (26.9)
Diarrhea (Cycle 4/Day 1) (n=826) 11.7  (25.6)
Diarrhea (Cycle 5/Day 1) (n=805) 12.6  (26.1)
Diarrhea (Cycle 6/Day 1) (n=772) 11.6  (26.4)
Diarrhea (Cycle 7/Day 1) (n=732) 10.9  (26.3)
Diarrhea (Cycle 8/Day 1) (n=698) 9.8  (25.6)
Diarrhea (Cycle 9/Day 1) (n=665) 10.5  (25.6)
Diarrhea (Cycle 10/Day 1) (n=632) 11.1  (26.6)
Diarrhea (Cycle 11/Day 1) (n=570) 10.1  (25.9)
Diarrhea (Cycle 12/Day 1) (n=411) 8.1  (25.2)
Diarrhea (Cycle 13/Day 1) (n=512) 8.8  (24.0)
Diarrhea (Cycle 14/Day 1) (n=352) 10.1  (22.4)
Diarrhea (Cycle 15/Day 1) (n=461) 8.5  (23.1)
Diarrhea (Cycle 16/Day 1) (n=293) 10.0  (22.5)
Diarrhea (Cycle 17/Day 1) (n=419) 8.6  (23.9)
Diarrhea (Cycle 18/Day 1) (n=247) 7.4  (22.4)
Diarrhea (Cycle 19/Day 1) (n=376) 7.8  (22.5)
Diarrhea (Cycle 20/Day 1) (n=222) 6.8  (22.6)
Diarrhea (Cycle 21/Day 1) (n=340) 6.6  (20.3)
Diarrhea (Cycle 22/Day 1) (n=179) 6.8  (24.2)
Diarrhea (Cycle 23/Day 1) (n=305) 8.7  (22.7)
Diarrhea (Cycle 24/Day 1) (n=154) 6.4  (23.1)
Diarrhea (Cycle 25/Day 1) (n=293) 10.1  (23.4)
Diarrhea (Cycle 26/Day 1) (n=127) 5.0  (23.8)
Diarrhea (Cycle 27/Day 1) (n=269) 8.3  (24.5)
Diarrhea (Cycle 28/Day 1) (n=119) 5.6  (20.5)
Diarrhea (Cycle 29/Day 1) (n=247) 9.7  (22.6)
Diarrhea (Cycle 30/Day 1) (n=106) 10.1  (25.3)
Diarrhea (End of treatment) (n=449) 5.9  (24.5)
Dyspnoea (Cycle 2/Day 1) (n=933) -9.8  (26.2)
Dyspnoea (Cycle 3/Day 1) (n=876) -11.4  (28.2)
Dyspnoea (Cycle 4/Day 1) (n=834) -12.3  (28.6)
Dyspnoea (Cycle 5/Day 1) (n=808) -12.2  (27.7)
Dyspnoea (Cycle 6/Day 1) (n=776) -13.7  (27.6)
Dyspnoea (Cycle 7/Day 1) (n=737) -13.8  (27.8)
Dyspnoea (Cycle 8/Day 1) (n=702) -13.8  (28.2)
Dyspnoea (Cycle 9/Day 1) (n=671) -13.3  (27.9)
Dyspnoea (Cycle 10/Day 1) (n=635) -13.4  (27.6)
Dyspnoea (Cycle 11/Day 1) (n=575) -15.0  (27.8)
Dyspnoea (Cycle 12/Day 1) (n=411) -13.1  (26.8)
Dyspnoea (Cycle 13/Day 1) (n=515) -13.1  (28.1)
Dyspnoea (Cycle 14/Day 1) (n=356) -12.7  (27.5)
Dyspnoea (Cycle 15/Day 1) (n=463) -12.6  (28.5)
Dyspnoea (Cycle 16/Day 1) (n=295) -12.2  (27.6)
Dyspnoea (Cycle 17/Day 1) (n=421) -11.8  (27.9)
Dyspnoea (Cycle 18/Day 1) (n=248) -11.5  (27.4)
Dyspnoea (Cycle 19/Day 1) (n=377) -14.2  (28.0)
Dyspnoea (Cycle 20/Day 1) (n=222) -9.2  (26.4)
Dyspnoea (Cycle 21/Day 1) (n=344) -13.4  (27.1)
Dyspnoea (Cycle 22/Day 1) (n=181) -8.8  (26.4)
Dyspnoea (Cycle 23/Day 1) (n=309) -10.9  (26.6)
Dyspnoea (Cycle 24/Day 1) (n=156) -8.5  (27.3)
Dyspnoea (Cycle 25/Day 1) (n=295) -10.5  (26.3)
Dyspnoea (Cycle 26/Day 1) (n=129) -10.1  (27.2)
Dyspnoea (Cycle 27/Day 1) (n=273) -9.3  (24.8)
Dyspnoea (Cycle 28/Day 1) (n=121) -12.1  (28.9)
Dyspnoea (Cycle 29/Day 1) (n=249) -8.8  (25.4)
Dyspnoea (Cycle 30/Day 1) (n=109) -11.6  (27.7)
Dyspnoea (End of treatment) (n=450) -4.2  (32.8)
Fatigue (Cycle 2/Day 1) (n=936) -4.8  (21.8)
Fatigue (Cycle 3/Day 1) (n=879) -8.9  (23.7)
Fatigue (Cycle 4/Day 1) (n=836) -11.4  (24.1)
Fatigue (Cycle 5/Day 1) (n=810) -12.0  (24.2)
Fatigue (Cycle 6/Day 1) (n=778) -13.7  (24.3)
Fatigue (Cycle 7/Day 1) (n=739) -14.0  (24.6)
Fatigue (Cycle 8/Day 1) (n=704) -15.3  (23.7)
Fatigue (Cycle 9/Day 1) (n=671) -14.9  (24.0)
Fatigue (Cycle 10/Day 1) (n=637) -14.4  (24.2)
Fatigue (Cycle 11/Day 1) (n=577) -13.7  (24.3)
Fatigue (Cycle 12/Day 1) (n=413) -12.2  (23.4)
Fatigue (Cycle 13/Day 1) (n=517) -13.4  (23.6)
Fatigue (Cycle 14/Day 1) (n=358) -13.2  (22.3)
Fatigue (Cycle 15/Day 1) (n=466) -13.1  (23.9)
Fatigue (Cycle 16/Day 1) (n=296) -11.3  (24.1)
Fatigue (Cycle 17/Day 1) (n=424) -11.3  (24.6)
Fatigue (Cycle 18/Day 1) (N=250) -10.4  (25.2)
Fatigue (Cycle 19/Day 1) (n=380) -11.9  (23.7)
Fatigue (Cycle 20/Day 1) (n=224) -10.6  (23.2)
Fatigue (Cycle 21/Day 1) (n=346) -11.0  (25.0)
Fatigue (Cycle 22/Day 1) (n=182) -8.4  (23.0)
Fatigue (Cycle 23/Day 1) (n=311) -8.7  (23.3)
Fatigue (Cycle 24/Day 1) (n=157) -6.7  (24.1)
Fatigue (Cycle 25/Day 1) (n=297) -7.9  (23.2)
Fatigue (Cycle 26/Day 1) (n=129) -12.1  (24.8)
Fatigue (Cycle 27/Day 1) (n=275) -7.0  (22.3)
Fatigue (Cycle 28/Day 1) (n=121) -6.7  (25.2)
Fatigue (Cycle 29/Day 1) (n=251) -7.1  (22.1)
Fatigue (Cycle 30/Day 1) (n=109) -7.2  (27.0)
Fatigue (End of treatment) (n=451) -5.3  (27.5)
Financial Difficulties (Cycle 2/Day 1) (n=928) -4.6  (24.1)
Financial Difficulties (Cycle 3/Day 1) (n=871) -4.2  (25.2)
Financial Difficulties (Cycle 4/Day 1) (n=827) -5.9  (25.7)
Financial Difficulties (Cycle 5/Day 1) (n=803) -5.1  (25.6)
Financial Difficulties (Cycle 6/Day 1) (n=772) -5.5  (25.4)
Financial Difficulties (Cycle 7/Day 1) (n=732) -6.2  (25.8)
Financial Difficulties (Cycle 8/Day 1) (n=697) -6.4  (26.0)
Financial Difficulties (Cycle 9/Day 1) (n=663) -5.8  (25.8)
Financial Difficulties (Cycle 10/Day 1) (n=631) -7.4  (25.0)
Financial Difficulties (Cycle 11/Day 1) (n=569) -6.6  (25.4)
Financial Difficulties (Cycle 12/Day 1) (n=410) -4.8  (25.4)
Financial Difficulties (Cycle 13/Day 1) (n=512) -6.3  (25.8)
Financial Difficulties (Cycle 14/Day 1) (n=352) -5.8  (25.4)
Financial Difficulties (Cycle 15/Day 1) (n=461) -6.1  (26.7)
Financial Difficulties (Cycle 16/Day 1) (n=294) -4.0  (23.8)
Financial Difficulties (Cycle 17/Day 1) (n=418) -5.5  (26.8)
Financial Difficulties (Cycle 18/Day 1) (n=247) -3.8  (25.2)
Financial Difficulties (Cycle 19/Day 1) (n=376) -5.9  (26.8)
Financial Difficulties (Cycle 20/Day 1) (n=220) -5.2  (25.4)
Financial Difficulties (Cycle 21/Day 1) (n=339) -4.2  (25.9)
Financial Difficulties (Cycle 22/Day 1) (n=177) -2.1  (23.1)
Financial Difficulties (Cycle 23/Day 1) (n=304) -4.4  (24.9)
Financial Difficulties (Cycle 24/Day 1) (n=153) -2.8  (27.3)
Financial Difficulties (Cycle 25/Day 1) (n=292) -4.6  (24.8)
Financial Difficulties (Cycle 26/Day 1) (n=126) -2.9  (26.0)
Financial Difficulties (Cycle 27/Day 1) (n=268) -4.8  (25.5)
Financial Difficulties (Cycle 28/Day 1) (n=119) -4.2  (29.9)
Financial Difficulties (Cycle 29/Day 1) (n=247) -5.5  (25.2)
Financial Difficulties (Cycle 30/Day 1) (n=105) -3.5  (26.5)
Financial Difficulties (End of treatment) (n=447) -2.2  (27.5)
Insomnia (Cycle 2/Day 1) (n=934) -7.6  (29.3)
Insomnia (Cycle 3/Day 1) (n=878) -11.3  (30.1)
Insomnia (Cycle 4/Day 1) (n=833) -13.0  (29.7)
Insomnia (Cycle 5/Day 1) (n=808) -12.8  (29.8)
Insomnia (Cycle 6/Day 1) (n=778) -13.3  (31.1)
Insomnia (Cycle 7/Day 1) (n=739) -13.9  (29.7)
Insomnia (Cycle 8/Day 1) (n=703) -12.6  (29.9)
Insomnia (Cycle 9/Day 1) (n=673) -13.2  (28.8)
Insomnia (Cycle 10/Day 1) (n=637) -13.2  (29.4)
Insomnia (Cycle 11/Day 1) (n=576) -12.2  (30.0)
Insomnia (Cycle 12/Day 1) (n=413) -11.3  (29.7)
Insomnia (Cycle 13/Day 1) (n=516) -13.0  (29.5)
Insomnia (Cycle 14/Day 1) (n=358) -11.7  (30.3)
Insomnia (Cycle 15/Day 1) (n=464) -12.4  (30.0)
Insomnia (Cycle 16/Day 1) (n=296) -10.9  (31.6)
Insomnia (Cycle 17/Day 1) (n=424) -10.8  (29.2)
Insomnia (Cycle 18/Day 1) (n=250) -10.4  (30.3)
Insomnia (Cycle 19/Day 1) (n=379) -12.6  (28.9)
Insomnia (Cycle 20/Day 1) (n=224) -11.5  (27.1)
Insomnia (Cycle 21/Day 1) (n=346) -10.2  (27.6)
Insomnia (Cycle 22/Day 1) (n=182) -7.9  (25.8)
Insomnia (Cycle 23/Day 1) (n=311) -10.5  (27.2)
Insomnia (Cycle 24/Day 1) (n=157) -5.7  (28.0)
Insomnia (Cycle 25/Day 1) (n=296) -7.7  (28.8)
Insomnia (Cycle 26/Day 1) (n=129) -10.9  (29.2)
Insomnia (Cycle 27/Day 1) (n=274) -10.1  (27.4)
Insomnia (Cycle 28/Day 1) (n=121) -6.9  (32.7)
Insomnia (Cycle 29/Day 1) (n=251) -8.4  (28.5)
Insomnia (Cycle 30/Day 1) (n=109) -11.3  (32.1)
Nausea and Vomiting (Cycle 2/Day 1) (n=936) 6.2  (23.1)
Nausea and Vomiting (Cycle 3/Day 1) (n=879) 2.4  (23.3)
Nausea and Vomiting (Cycle 4/Day 1) (n=836) 0.3  (22.6)
Nausea and Vomiting (Cycle 5/Day 1) (n=810) -0.4  (21.1)
Nausea and Vomiting (Cycle 6/Day 1) (n=779) -1.6  (19.9)
Nausea and Vomiting (Cycle 7/Day 1) (n=739) -2.3  (21.0)
Nausea and Vomiting (Cycle 8/Day 1) (n=704) -1.9  (19.8)
Nausea and Vomiting (Cycle 9/Day 1) (n=673) -1.8  (21.2)
Nausea and Vomiting (Cycle 10/Day 1) (n=637) -1.4  (21.6)
Nausea and Vomiting (Cycle 11/Day 1) (n=577) -1.7  (20.9)
Nausea and Vomiting (Cycle 12/Day 1) (n=413) -1.5  (21.8)
Nausea and Vomiting (Cycle 13/Day 1) (n=517) -0.7  (21.2)
Nausea and Vomiting (Cycle 14/Day 1) (n=358) -0.4  (23.3)
Nausea and Vomiting (Cycle 15/Day 1) (n=466) -0.7  (21.2)
Nausea and Vomiting (Cycle 16/Day 1) (n=296) -0.8  (19.5)
Nausea and Vomiting (Cycle 17/Day 1) (n=424) -0.3  (20.2)
Nausea and Vomiting (Cycle 18/Day 1) (n=250) -0.9  (21.7)
Nausea and Vomiting (Cycle 19/Day 1) (n=380) -0.3  (20.1)
Nausea and Vomiting (Cycle 20/Day 1) (n=224) -2.3  (18.7)
Nausea and Vomiting (Cycle 21/Day 1) (n=346) -1.1  (18.6)
Nausea and Vomiting (Cycle 22/Day 1) (n=182) 0.2  (19.0)
Nausea and Vomiting (Cycle 23/Day 1) (n=311) 0.8  (17.4)
Nausea and Vomiting (Cycle 24/Day 1) (n=157) -1.3  (17.4)
Nausea and Vomiting (Cycle 25/Day 1) (n=297) 0.6  (18.0)
Nausea and Vomiting (Cycle 26/Day 1) (n=129) -2.3  (20.2)
Nausea and Vomiting (Cycle 27/Day 1) (n=275) 1.9  (17.5)
Nausea and Vomiting (Cycle 28/Day 1) (n=121) 1.8  (19.7)
Nausea and Vomiting (Cycle 29/Day 1) (n=251) 2.5  (18.9)
Nausea and Vomiting (Cycle 30/Day 1) (n=109) -0.5  (17.5)
Nausea and Vomiting (End of treatment) (n=451) 4.0  (25.3)
Pain (Cycle 2/Day 1) (n=935) -13.1  (26.6)
Pain (Cycle 3/Day 1) (n=880) -16.0  (28.0)
Pain (Cycle 4/Day 1) (n=836) -15.7  (27.8)
Pain (Cycle 5/Day 1) (n=810) -15.5  (27.4)
Pain (Cycle 6/Day 1) (n=779) -15.5  (27.8)
Pain (Cycle 7/Day 1) (n=739) -16.0  (29.0)
Pain (Cycle 8/Day 1) (n=705) -15.9  (28.5)
Pain (Cycle 9/Day 1) (n=673) -15.5  (28.7)
Pain (Cycle 10/Day 1) (n=637) -15.1  (27.6)
Pain (Cycle 11/Day 1) (n=577) -14.6  (27.6)
Pain (Cycle 12/Day 1) (n=414) -13.6  (29.2)
Pain (Cycle 13/Day 1) (n=517) -13.8  (28.0)
Pain (Cycle 14/Day 1) (n=357) -13.9  (29.5)
Pain (Cycle 15/Day 1) (n=466) -12.1  (27.0)
Pain (Cycle 16/Day 1) (n=296) -12.5  (27.9)
Pain (Cycle 17/Day 1) (n=424) -10.6  (25.6)
Pain (Cycle 18/Day 1) (n=250) -11.1  (27.5)
Pain (Cycle 19/Day 1) (n=380) -10.8  (24.1)
Pain (Cycle 20/Day 1) (n=224) -11.0  (27.2)
Pain (Cycle 21/Day 1) (n=346) -10.1  (25.2)
Pain (Cycle 22/Day 1) (n=182) -7.7  (26.2)
Pain (Cycle 23/Day 1) (n=311) -7.4  (26.0)
Pain (Cycle 24/Day 1) (n=157) -8.8  (27.7)
Pain (Cycle 25/Day 1) (n=297) -8.8  (24.6)
Pain (Cycle 26/Day 1) (n=129) -12.5  (29.5)
Pain (Cycle 27/Day 1) (n=275) -7.6  (25.3)
Pain (Cycle 28/Day 1) (n=121) -7.9  (32.4)
Pain (Cycle 29/Day 1) (n=251) -8.1  (24.6)
Pain (Cycle 30/Day 1) (n=109) -7.5  (29.8)
Pain (End of treatment) (n=451) -5.3  (31.2)
Insomnia (End of treatment) 9n=451) -5.7  (33.6)
15.Secondary Outcome
Title Mean Change From Baseline of QLQ-LC13 Scale Scores
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 976
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Alopecia (Cycle 2/Day 1) (n=920) -9.1  (29.6)
Alopecia (Cycle 3/Day 1) (n=870) -10.2  (31.6)
Alopecia (Cycle 4/Day 1) (n=829) -11.6  (30.7)
Alopecia (Cycle 5/Day 1) (n=805) -12.2  (32.3)
Alopecia (Cycle 6/Day 1) (n=770) -10.5  (30.9)
Alopecia (Cycle 7/Day 1) (n=734) -11.9  (32.3)
Alopecia (Cycle 8/Day 1) (n=700) -11.9  (33.2)
Alopecia (Cycle 9/Day 1) (n=667) -11.3  (34.7)
Alopecia (Cycle 10/Day 1) (n=633) -10.8  (33.9)
Alopecia (Cycle 11/Day 1) (n=574) -11.3  (34.8)
Alopecia (Cycle 12/Day 1) (n=409) -7.8  (34.8)
Alopecia (Cycle 13/Day 1) (n=512) -10.8  (35.0)
Alopecia (Cycle 14/Day 1) (n=353) -8.2  (36.4)
Alopecia (Cycle 15/Day 1) (n=462) -11.8  (34.3)
Alopecia (Cycle 16/Day 1) (n=293) -7.7  (34.1)
Alopecia (Cycle 17/Day 1) (n=419) -9.5  (32.9)
Alopecia (Cycle 18/Day 1) (n=247) -6.4  (31.3)
Alopecia (Cycle 19/Day 1) (n=377) -8.9  (34.1)
Alopecia (Cycle 20/Day 1) (n=222) -9.0  (30.7)
Alopecia (Cycle 21/Day 1) (n=342) -7.8  (32.9)
Alopecia (Cycle 22/Day 1) (n=180) -7.6  (35.6)
Alopecia (Cycle 23/Day 1) (n=310) -7.0  (33.2)
Alopecia (Cycle 24/Day 1) (n=156) -4.1  (34.1)
Alopecia (Cycle 25/Day 1) (n=293) -8.2  (31.8)
Alopecia (Cycle 26/Day 1) (n=126) -4.5  (31.1)
Alopecia (Cycle 27/Day 1) (n=271) -8.5  (31.5)
Alopecia (Cycle 28/Day 1) (n=119) -3.9  (33.1)
Alopecia (Cycle 29/Day 1) (n=247) -9.2  (28.3)
Alopecia (Cycle 30/Day 1) (n=107) -5.0  (31.7)
Alopecia (End of treatment) (n=447) -9.9  (35.3)
Coughing (Cycle 2/Day 1) (n=926) -12.9  (28.8)
Coughing (Cycle 3/Day 1) (n=879) -15.5  (31.8)
Coughing (Cycle 4/Day 1) (n=832) -17.7  (31.1)
Coughing (Cycle 5/Day 1) (n=807) -17.3  (31.8)
Coughing (Cycle 6/Day 1) (n=775) -18.3  (32.1)
Coughing (Cycle 7/Day 1) (n=735) -20.1  (32.2)
Coughing (Cycle 8/Day 1) (n=703) -20.8  (31.8)
Coughing (Cycle 9/Day 1) (n=669) -20.2  (30.9)
Coughing (Cycle 10/Day 1) (n=636) -19.9  (32.0)
Coughing (Cycle 11/Day 1) (n=575) -19.9  (31.6)
Coughing (Cycle 12/Day 1) (n=414) -19.2  (29.5)
Coughing (Cycle 13/Day 1) (n=513) -18.6  (32.6)
Coughing (Cycle 14/Day 1) (n=355) -17.9  (32.1)
Coughing (Cycle 15/Day 1) (n=461) -17.8  (31.7)
Coughing (Cycle 16/Day 1) (n=294) -17.3  (29.5)
Coughing (Cycle 17/Day 1) (n=421) -18.4  (32.5)
Coughing (Cycle 18/Day 1) (n=249) -16.9  (33.1)
Coughing (Cycle 19/Day 1) (n=379) -18.8  (30.3)
Coughing (Cycle 20/Day 1) (n=222) -18.3  (32.7)
Coughing (Cycle 21/Day 1) (n=343) -18.0  (31.0)
Coughing (Cycle 22/Day 1) (n=181) -16.7  (33.1)
Coughing (Cycle 23/Day 1) (n=311) -18.4  (32.1)
Coughing (Cycle 24/Day 1) (n=155) -18.9  (31.3)
Coughing (Cycle 25/Day 1) (n=294) -18.1  (31.3)
Coughing (Cycle 26/Day 1) (n=125) -21.9  (30.8)
Coughing (Cycle 27/Day 1) (n=272) -17.8  (32.2)
Coughing (Cycle 28/Day 1) (n=119) -19.6  (30.8)
Coughing (Cycle 29/Day 1) (n=249) -17.1  (31.3)
Coughing (Cycle 30/Day 1) (n=106) -16.7  (29.5)
Coughing (End of treatment) (n=452) -11.1  (33.5)
Dysphagia (Cycle 2/Day 1) (n=926) 0.0  (19.6)
Dysphagia (Cycle 3/Day 1) (n=879) -1.1  (20.1)
Dysphagia (Cycle 4/Day 1) (n=831) -2.2  (20.8)
Dysphagia (Cycle 5/Day 1) (n=807) -2.3  (20.0)
Dysphagia (Cycle 6/Day 1) (n=776) -3.0  (19.9)
Dysphagia (Cycle 7/Day 1) (n=737) -3.1  (20.7)
Dysphagia (Cycle 8/Day 1) (n=702) -3.1  (18.6)
Dysphagia (Cycle 9/Day 1) (n=670) -2.7  (20.2)
Dysphagia (Cycle 10/Day 1) (n=637) -2.9  (19.4)
Dysphagia (Cycle 11/Day 1) (n=577) -3.0  (19.2)
Dysphagia (Cycle 12/Day 1) (n=414) -2.7  (18.1)
Dysphagia (Cycle 13/Day 1) (n=513) -3.1  (17.8)
Dysphagia (Cycle 14/Day 1) (n=355) -1.7  (18.2)
Dysphagia (Cycle 15/Day 1) (n=463) -2.8  (17.5)
Dysphagia (Cycle 16/Day 1) (n=294) -1.3  (20.1)
Dysphagia (Cycle 17/Day 1) (n=422) -2.2  (19.0)
Dysphagia (Cycle 18/Day 1) (n=249) -2.5  (18.4)
Dysphagia (Cycle 19/Day 1) (n=378) -2.0  (17.3)
Dysphagia (Cycle 20/Day 1) (n=223) -3.4  (18.5)
Dysphagia (Cycle 21/Day 1) (n=344) -2.5  (18.2)
Dysphagia (Cycle 22/Day 1) (n=182) -1.8  (19.7)
Dysphagia (Cycle 23/Day 1) (n=311) -3.4  (17.0)
Dysphagia (Cycle 24/Day 1) (n=156) -1.4  (16.5)
Dysphagia (Cycle 25/Day 1) (n=295) -2.8  (17.3)
Dysphagia (Cycle 26/Day 1) (n=126) -1.1  (15.7)
Dysphagia (Cycle 27/Day 1) (n=274) -1.6  (17.5)
Dysphagia (Cycle 28/Day 1) (n=120) -1.4  (16.4)
Dysphagia (Cycle 29/Day 1) (n=248) -1.5  (16.5)
Dysphagia (Cycle 30/Day 1) (n=107) -0.9  (18.0)
Dysphagia (End of treatment) (n=449) 1.9  (23.5)
Dyspnoea (Cycle 2/Day 1) (n=928) -8.0  (19.0)
Dyspnoea (Cycle 3/Day 1) (n=878) -9.7  (21.5)
Dyspnoea (Cycle 4/Day 1) (n=833) -10.7  (21.7)
Dyspnoea (Cycle 5/Day 1) (n=809) -10.6  (21.4)
Dyspnoea (Cycle 6/Day 1) (n=775) -10.6  (21.7)
Dyspnoea (Cycle 7/Day 1) (n=737) -11.1  (21.1)
Dyspnoea (Cycle 8/Day 1) (n=704) -12.0  (20.7)
Dyspnoea (Cycle 9/Day 1) (n=669) -11.0  (20.7)
Dyspnoea (Cycle 10/Day 1) (n=637) -10.7  (21.1)
Dyspnoea (Cycle 12/Day 1) (n=414) -9.0  (20.2)
Dyspnoea (Cycle 13/Day 1) (n=514) -9.8  (21.1)
Dyspnoea (Cycle 14/Day 1) (n=354) -9.2  (20.0)
Dyspnoea (Cycle 15/Day 1) (n=463) -8.9  (21.6)
Dyspnoea (Cycle 16/Day 1) (n=293) -7.7  (21.3)
Dyspnoea (Cycle 17/Day 1) (n=421) -7.3  (20.5)
Dyspnoea (Cycle 18/Day 1) (n=249) -6.9  (21.3)
Dyspnoea (Cycle 19/Day 1) (n=379) -8.6  (19.7)
Dyspnoea (Cycle 20/Day 1) (n=223) -5.8  (19.8)
Dyspnoea (Cycle 21/Day 1) (n=344) -7.8  (19.5)
Dyspnoea (Cycle 22/Day 1) (n=182) -5.6  (18.3)
Dyspnoea (Cycle 23/Day 1) (n=311) -6.1  (19.3)
Dyspnoea (Cycle 24/Day 1) (n=156) -6.2  (18.3)
Dyspnoea (Cycle 25/Day 1) (n=295) -6.1  (19.7)
Dyspnoea (Cycle 26/Day 1) (n=126) -6.6  (19.3)
Dyspnoea (Cycle 27/Day 1) (n=273) -5.7  (19.0)
Dyspnoea (Cycle 28/Day 1) (n=120) -5.8  (19.5)
Dyspnoea (Cycle 29/Day 1) (n=249) -3.9  (19.2)
Dyspnoea (Cycle 30/Day 1) (n=107) -4.6  (17.5)
Dyspnoea (End of treatment) (n=448) -3.0  (25.7)
Haemoptysis (Cycle 2/Day 1) (n=925) -2.6  (12.6)
Haemoptysis (Cycle 3/Day 1) (n=879) -3.0  (12.6)
Haemoptysis (Cycle 4/Day 1) (n=833) -2.9  (12.7)
Haemoptysis (Cycle 5/Day 1) (n=808) -2.6  (12.9)
Haemoptysis (Cycle 6/Day 1) (n=774) -2.8  (12.0)
Haemoptysis (Cycle 7/Day 1) (n=735) -2.9  (12.7)
Haemoptysis (Cycle 8/Day 1) (n=703) -3.1  (11.9)
Haemoptysis (Cycle 9/Day 1) (n=669) -3.0  (11.7)
Haemoptysis (Cycle 10/Day 1) (n=635) -2.6  (11.7)
Haemoptysis (Cycle 11/Day 1) (n=576) -2.7  (11.6)
Haemoptysis (Cycle 12/Day 1) (n=413) -2.6  (10.3)
Haemoptysis (Cycle 13/Day 1) (n=514) -2.1  (12.0)
Haemoptysis (Cycle 14/Day 1) (n=354) -2.7  (11.3)
Haemoptysis (Cycle 15/Day 1) (n=462) -2.2  (10.8)
Haemoptysis (Cycle 16/Day 1) (n=294) -2.5  (11.4)
Haemoptysis (Cycle 17/Day 1) (n=420) -1.9  (11.4)
Haemoptysis (Cycle 18/Day 1) (n=249) -2.4  (12.1)
Haemoptysis (Cycle 19/Day 1) (n=378) -2.1  (11.5)
Haemoptysis (Cycle 20/Day 1) (n=223) -2.4  (13.6)
Haemoptysis (Cycle 21/Day 1) (n=342) -2.5  (11.5)
Haemoptysis (Cycle 22/Day 1) (n=182) -2.9  (11.2)
Haemoptysis (Cycle 23/Day 1) (n=309) -2.7  (12.5)
Haemoptysis (Cycle 24/Day 1) (n=156) -2.4  (12.0)
Haemoptysis (Cycle 25/Day 1) (n=294) -2.8  (12.4)
Haemoptysis (Cycle 26/Day 1) (n=126) -3.2  (12.9)
Haemoptysis (Cycle 27/Day 1) (n=272) -2.9  (11.4)
Haemoptysis (Cycle 28/Day 1) (n=119) -3.1  (12.3)
Haemoptysis (Cycle 29/Day 1) (n=248) -1.7  (12.1)
Haemoptysis (Cycle 30/Day 1) (n=107) -2.8  (11.3)
Haemoptysis (End of treatment) (n=451) -1.4  (15.9)
Pain in Arm or Shoulder (Cycle 2/Day 1) (n=926) -9.6  (26.9)
Pain in Arm or Shoulder (Cycle 3/Day 1) (n=876) -12.2  (27.0)
Pain in Arm or Shoulder (Cycle 4/Day 1) (n=832) -12.5  (28.2)
Pain in Arm or Shoulder (Cycle 5/Day 1) (n=807) -11.7  (27.1)
Pain in Arm or Shoulder (Cycle 6/Day 1) (n=773) -11.6  (26.3)
Pain in Arm or Shoulder (Cycle 7/Day 1) (n=738) -11.3  (28.1)
Pain in Arm or Shoulder (Cycle 8/Day 1) (n=702) -11.7  (28.5)
Pain in Arm or Shoulder (Cycle 9/Day 1) (n=669) -11.9  (28.5)
Pain in Arm or Shoulder (Cycle 10/Day 1) (n=635) -11.3  (28.0)
Pain in Arm or Shoulder (Cycle 11/Day 1) (n=576) -12.1  (27.3)
Pain in Arm or Shoulder (Cycle 12/Day 1) (n=414) -11.0  (27.7)
Pain in Arm or Shoulder (Cycle 13/Day 1) (n=513) -10.9  (27.2)
Pain in Arm or Shoulder (Cycle 14/Day 1) (n=355) -11.3  (27.3)
Pain in Arm or Shoulder (Cycle 15/Day 1) (n=461) -10.3  (25.6)
Pain in Arm or Shoulder (Cycle 16/Day 1) (n=293) -9.9  (28.0)
Pain in Arm or Shoulder (Cycle 17/Day 1) (n=421) -8.2  (26.5)
Pain in Arm or Shoulder (Cycle 18/Day 1) (n=249) -9.4  (27.6)
Pain in Arm or Shoulder (Cycle 19/Day 1) (n=379) -9.1  (26.5)
Pain in Arm or Shoulder (Cycle 20/Day 1) (n=222) -7.4  (27.3)
Pain in Arm or Shoulder (Cycle 21/Day 1) (n=344) -9.0  (27.0)
Pain in Arm or Shoulder (Cycle 22/Day 1) (n=182) -9.0  (29.1)
Pain in Arm or Shoulder (Cycle 23/Day 1) (n=311) -8.9  (25.5)
Pain in Arm or Shoulder (Cycle 24/Day 1) (n=155) -9.7  (30.6)
Pain in Arm or Shoulder (Cycle 25/Day 1) (n=295) -9.2  (26.0)
Pain in Arm or Shoulder (Cycle 26/Day 1) (n=126) -10.8  (33.7)
Pain in Arm or Shoulder (Cycle 27/Day 1) (n=274) -8.6  (26.5)
Pain in Arm or Shoulder (Cycle 28/Day 1) (n=119) -8.7  (29.6)
Pain in Arm or Shoulder (Cycle 29/Day 1) (n=248) -7.9  (27.2)
Pain in Arm or Shoulder (Cycle 30/Day 1) (n=107) -8.1  (30.3)
Pain in Arm or Shoulder (End of treatment) (n=445) -5.8  (30.7)
Pain in Chest (Cycle 2/Day 1) (n=928) -9.5  (23.4)
Pain in Chest (Cycle 3/Day 1) (n=875) -11.9  (25.1)
Pain in Chest (Cycle 4/Day 1) (n=833) -12.1  (26.1)
Pain in Chest (Cycle 5/Day 1) (n=808) -11.8  (25.8)
Pain in Chest (Cycle 6/Day 1) (n=774) -12.1  (25.3)
Pain in Chest (Cycle 7/Day 1) (n=735) -12.6  (25.4)
Pain in Chest (Cycle 8/Day 1) (n=703) -13.2  (25.0)
Pain in Chest (Cycle 9/Day 1) (n=665) -13.1  (25.8)
Pain in Chest (Cycle 10/Day 1) (n=633) -12.9  (26.0)
Pain in Chest (Cycle 11/Day 1) (n=574) -12.0  (25.5)
Pain in Chest (Cycle 12/Day 1) (n=414) -10.7  (25.5)
Pain in Chest (Cycle 13/Day 1) (n=513) -12.6  (24.5)
Pain in Chest (Cycle 14/Day 1) (n=355) -11.5  (24.4)
Pain in Chest (Cycle 15/Day 1) (n=462) -11.9  (24.7)
Pain in Chest (Cycle 16/Day 1) (n=294) -11.0  (23.4)
Pain in Chest (Cycle 17/Day 1) (n=421) -11.6  (23.8)
Pain in Chest (Cycle 18/Day 1) (n=249) -8.0  (23.1)
Pain in Chest (Cycle 19/Day 1) (n=378) -11.2  (23.8)
Pain in Chest (Cycle 20/Day 1) (n=222) -9.4  (24.3)
Pain in Chest (Cycle 21/Day 1) (n=343) -11.9  (23.5)
Pain in Chest (Cycle 22/Day 1) (n=182) -10.1  (21.9)
Pain in Chest (Cycle 23/Day 1) (n=308) -10.8  (24.0)
Pain in Chest (Cycle 24/Day 1) (n=156) -7.1  (26.8)
Pain in Chest (Cycle 25/Day 1) (n=293) -10.2  (22.3)
Pain in Chest (Cycle 26/Day 1) (n=126) -10.6  (25.2)
Pain in Chest (Cycle 27/Day 1) (n=272) -9.2  (22.0)
Pain in Chest (Cycle 28/Day 1) (n=120) -9.4  (26.7)
Pain in Chest (Cycle 29/Day 1) (n=248) -9.5  (24.4)
Pain in Chest (Cycle 30/Day 1) (n=107) -5.3  (26.8)
Pain in Chest (End of treatment) (n=451) -6.7  (28.0)
Pain in Other Parts (Cycle 2/Day 1) (n=893) -10.0  (31.3)
Pain in Other Parts (Cycle 3/Day 1) (n=854) -12.0  (31.9)
Pain in Other Parts (Cycle 4/Day 1) (n=806) -13.5  (31.0)
Pain in Other Parts (Cycle 5/Day 1) (n=793) -12.2  (30.2)
Pain in Other Parts (Cycle 6/Day 1) (n=752) -12.5  (30.9)
Pain in Other Parts (Cycle 7/Day 1) (n=715) -11.8  (30.3)
Pain in Other Parts (Cycle 8/Day 1) (n=680) -11.7  (30.5)
Pain in Other Parts (Cycle 9/Day 1) (n=650) -13.1  (29.9)
Pain in Other Parts (Cycle 10/Day 1) (n=616) -12.1  (30.4)
Pain in Other Parts (Cycle 11/Day 1) (n=562) -10.8  (29.3)
Pain in Other Parts (Cycle 12/Day 1) (n=399) -11.6  (30.9)
Pain in Other Parts (Cycle 13/Day 1) (n=499) -9.9  (30.0)
Pain in Other Parts (Cycle 14/Day 1) (n=342) -11.5  (31.3)
Pain in Other Parts (Cycle 15/Day 1) (n=451) -10.1  (28.9)
Pain in Other Parts (Cycle 16/Day 1) (n=282) -9.6  (30.3)
Pain in Other Parts (Cycle 17/Day 1) (n=411) -8.8  (28.1)
Pain in Other Parts (Cycle 18/Day 1) (n=239) -8.6  (31.0)
Pain in Other Parts (Cycle 19/Day 1) (n=370) -8.8  (29.0)
Pain in Other Parts (Cycle 20/Day 1) (n=210) -9.4  (31.3)
Pain in Other Parts (Cycle 21/Day 1) (n=337) -8.2  (28.6)
Pain in Other Parts (Cycle 22/Day 1) (n=176) -10.4  (30.2)
Pain in Other Parts (Cycle 23/Day 1) (n=300) -6.6  (29.2)
Pain in Other Parts (Cycle 24/Day 1) (n=149) -7.8  (35.2)
Pain in Other Parts (Cycle 25/Day 1) (n=286) -7.2  (30.2)
Pain in Other Parts (Cycle 26/Day 1) (n=121) -8.8  (34.6)
Pain in Other Parts (Cycle 27/Day 1) (n=267) -5.9  (29.5)
Pain in Other Parts (Cycle 28/Day 1) (n=116) -3.2  (34.6)
Pain in Other Parts (Cycle 29/Day 1) (n=242) -6.3  (27.1)
Pain in Other Parts (Cycle 30/Day 1) (n=102) -6.5  (34.8)
Pain in Other Parts (End of treatment) (n=427) -4.6  (34.8)
Peripheral Neuropathy (Cycle 2/Day 1) (n=925) 0.6  (25.3)
Peripheral Neuropathy (Cycle 3/Day 1) (n=876) -0.4  (25.6)
Peripheral Neuropathy (Cycle 4/Day 1) (n=833) -1.7  (26.5)
Peripheral Neuropathy (Cycle 5/Day 1) (n=807) -1.2  (26.3)
Peripheral Neuropathy (Cycle 6/Day 1) (n=775) -1.4  (26.5)
Peripheral Neuropathy (Cycle 7/Day 1) (n=737) -2.6  (27.2)
Peripheral Neuropathy (Cycle 8/Day 1) (n=703) -2.1  (25.6)
Peripheral Neuropathy (Cycle 9/Day 1) (n=668) -1.8  (27.2)
Peripheral Neuropathy (Cycle 10/Day 1) (n=635) -1.0  (26.4)
Peripheral Neuropathy (Cycle 11/Day 1) (n=575) -1.6  (27.5)
Peripheral Neuropathy (Cycle 12/Day 1) (n=413) -0.8  (27.3)
Peripheral Neuropathy (Cycle 13/Day 1) (n=512) -1.5  (27.0)
Peripheral Neuropathy (Cycle 14/Day 1) (n=354) -2.1  (28.6)
Peripheral Neuropathy (Cycle 15/Day 1) (n=462) -0.7  (27.5)
Peripheral Neuropathy (Cycle 16/Day 1) (n=294) -1.5  (29.9)
Peripheral Neuropathy (Cycle 17/Day 1) (n=418) -0.3  (28.3)
Peripheral Neuropathy (Cycle 18/Day 1) (n=249) -0.7  (28.3)
Peripheral Neuropathy (Cycle 19/Day 1) (n=378) -1.5  (23.9)
Peripheral Neuropathy (Cycle 20/Day 1) (n=221) -0.0  (28.1)
Peripheral Neuropathy (Cycle 21/Day 1) (n=342) 0.2  (27.6)
Peripheral Neuropathy (Cycle 22/Day 1) (n=182) -3.7  (27.6)
Peripheral Neuropathy (Cycle 23/Day 1) (n=310) -1.0  (26.2)
Peripheral Neuropathy (Cycle 24/Day 1) (n=156) -1.7  (26.4)
Peripheral Neuropathy (Cycle 25/Day 1) (n=295) 2.3  (25.5)
Peripheral Neuropathy (Cycle 26/Day 1) (n=126) -1.6  (24.9)
Peripheral Neuropathy (Cycle 27/Day 1) (n=274) 2.1  (27.1)
Peripheral Neuropathy (Cycle 28/Day 1) (n=119) -0.6  (27.1)
Peripheral Neuropathy (Cycle 29/Day 1) (n=249) 1.5  (26.3)
Peripheral Neuropathy (Cycle 30/Day 1) (n=107) -0.6  (28.2)
Peripheral Neuropathy (End of treatment) (n=451) -0.6  (26.6)
Sore Mouth (Cycle 2/Day 1) (n=928) 1.0  (20.0)
Sore Mouth (Cycle 3/Day 1) (n=879) -0.2  (19.8)
Sore Mouth (Cycle 4/Day 1) (n=834) -0.6  (19.1)
Sore Mouth (Cycle 5/Day 1) (n=808) -1.3  (17.9)
Sore Mouth (Cycle 6/Day 1) (n=776) -1.8  (17.1)
Sore Mouth (Cycle 7/Day 1) (n=738) -1.2  (18.3)
Sore Mouth (Cycle 8/Day 1) (n=704) -2.2  (17.0)
Sore Mouth (Cycle 9/Day 1) (n=669) -2.1  (18.3)
Sore Mouth (Cycle 10/Day 1) (n=636) -1.7  (19.1)
Sore Mouth (Cycle 11/Day 1) (n=577) -1.8  (17.2)
Sore Mouth (Cycle 12/Day 1) (n=414) -1.9  (17.1)
Sore Mouth (Cycle 13/Day 1) (n=514) -1.5  (18.0)
Sore Mouth (Cycle 14/Day 1) (n=354) -1.3  (14.8)
Sore Mouth (Cycle 15/Day 1) (n=463) -0.9  (16.1)
Sore Mouth (Cycle 16/Day 1) (n=294) 0.1  (16.6)
Sore Mouth (Cycle 17/Day 1) (n=422) -1.4  (17.6)
Sore Mouth (Cycle 18/Day 1) (n=249) -0.9  (18.0)
Sore Mouth (Cycle 19/Day 1) (n=379) -0.9  (17.3)
Sore Mouth (Cycle 20/Day 1) (n=223) -1.3  (17.7)
Sore Mouth (Cycle 21/Day 1) (n=344) -0.6  (18.0)
Sore Mouth (Cycle 22/Day 1) (n=182) -1.1  (14.8)
Sore Mouth (Cycle 23/Day 1) (n=311) 0.3  (17.7)
Sore Mouth (Cycle 24/Day 1) (n=156) 2.6  (17.2)
Sore Mouth (Cycle 25/Day 1) (n=294) -1.6  (17.6)
Sore Mouth (Cycle 26/Day 1) (n=126) -2.4  (14.7)
Sore Mouth (Cycle 27/Day 1) (n=274) -0.6  (18.4)
Sore Mouth (Cycle 28/Day 1) (n=120) -0.3  (15.3)
Sore Mouth (Cycle 29/Day 1) (n=249) -1.7  (16.4)
Sore Mouth (Cycle 30/Day 1) (n=107) -1.2  (12.9)
Sore Mouth (End of treatment) (n=451) -0.4  (20.0)
16.Secondary Outcome
Title Percentage of Participants With Visual Symptom Assessment Questionnaire (VSAQ-ALK)
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 1066
Measure Type: Number
Unit of Measure: Percentage of participants
Cycle 2/Day 1 (Yes) (N=798) 64.5
Cycle 2/Day 1 (No) (N=798) 35.5
Cycle 3/Day 1 (Yes) (N=768) 56.5
Cycle 3/Day 1 (No) (N=768) 43.5
Cycle 4/Day 1 (Yes) (N=754) 52.3
Cycle 4/Day 1 (No) (N=754) 47.7
Cycle 5/Day 1 (Yes) (N=743) 49.1
Cycle 5/Day 1 (No) (N=743) 50.9
Cycle 6/Day 1 (Yes) (N=731) 48.8
Cycle 6/Day 1 (No) (N=731) 51.2
Cycle 7/Day 1 (Yes) (N=699) 45.8
Cycle 7/Day 1 (No) (N=699) 54.2
Cycle 8/Day 1 (Yes) (N=670) 43.7
Cycle 8/Day 1 (No) (N=670) 56.3
Cycle 9/Day 1 (Yes) (N=653) 43.5
Cycle 9/Day 1 (No) (N=653) 56.5
Cycle 10/Day 1 (Yes) (N=621) 42.7
Cycle 10/Day 1 (No) (N=621) 57.3
Cycle 11/Day 1 (Yes) (N=565) 40.2
Cycle 11/Day 1 (No) (N=565) 59.8
Cycle 12/Day 1 (Yes) (N=403) 42.9
Cycle 12/Day 1 (No) (N=403) 57.1
Cycle 13/Day 1 (Yes) (N=507) 41.2
Cycle 13/Day 1 (No) (N=507) 58.8
Cycle 14/Day 1 (Yes) (N=354) 41.5
Cycle 14/Day 1 (No) (N=354) 58.5
Cycle 15/Day 1 (Yes) (N=468) 39.1
Cycle 15/Day 1 (No) (N=468) 60.9
Cycle 16/Day 1 (Yes) (N=296) 43.6
Cycle 16/Day 1 (No) (N=296) 56.4
Cycle 17/Day 1 (Yes) (N=418) 37.3
Cycle 17/Day 1 (No) (N=418) 62.7
Cycle 18/Day 1 (Yes) (N=249) 40.2
Cycle 18/Day 1 (No) (N=249) 59.8
Cycle 19/Day 1 (Yes) (N=378) 36.8
Cycle 19/Day 1 (No) (N=378) 63.2
Cycle 20/Day 1 (Yes) (N=221) 38.9
Cycle 20/Day 1 (No) (N=221) 61.1
Cycle 21/Day 1 (Yes) (N=344) 39.0
Cycle 21/Day 1 (No) (N=344) 61.0
Cycle 22/Day 1 (Yes) (N=181) 39.2
Cycle 22/Day 1 (No) (N=181) 60.8
Cycle 23/Day 1 (Yes) (N=312) 34.9
Cycle 23/Day 1 (No) (N=312) 65.1
Cycle 24/Day 1 (Yes) (N=155) 34.8
Cycle 24/Day 1 (No) (N=155) 65.2
Cycle 25/Day 1 (Yes) (N=302) 35.8
Cycle 25/Day 1 (No) (N=302) 64.2
Cycle 26/Day 1 (Yes) (N=130) 30.8
Cycle 26/Day 1 (No) (N=130) 69.2
Cycle 27/Day 1 (Yes) (N=276) 32.6
Cycle 27/Day 1 (No) (N=276) 67.4
Cycle 28/Day 1 (Yes) (N=118) 31.4
Cycle 28/Day 1 (No) (N=118) 68.6
Cycle 29/Day 1 (Yes) (N=249) 30.5
Cycle 29/Day 1 (No) (N=249) 69.5
Cycle 30/Day 1 (Yes) (N=106) 27.4
Cycle 30/Day 1 (No) (N=106) 72.6
End of Treatment (Yes) (N=428) 39.3
End of Treatment (No) (N=428) 60.7
17.Secondary Outcome
Title Patient Reported Outcomes (PROs) of Health-related Quality of Life (HRQoL): Mean Change From Baseline of EQ-5D Visual Analog Score (VAS) Scale
Hide Description 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.
Time Frame 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 974
Mean (Standard Deviation)
Unit of Measure: Units on a scale
CYCLE 2/DAY 1 (n=926) 5.72  (17.51)
CYCLE 3/DAY 1 (n=875) 8.57  (18.82)
CYCLE 4/DAY 1 (n=836) 10.01  (19.73)
CYCLE 5/DAY 1 (n=804) 10.38  (19.85)
CYCLE 6/DAY 1 (n=771) 10.17  (20.38)
CYCLE 7/DAY 1 (n=728) 10.17  (20.38)
CYCLE 8/DAY 1 (n=693) 10.35  (19.22)
CYCLE 9/DAY 1 (n=667) 10.69  (19.82)
CYCLE 10/DAY 1 (n=633) 10.34  (19.15)
CYCLE 11/DAY 1 (n=573) 10.09  (19.72)
CYCLE 12/DAY 1 (n=409) 9.69  (18.81)
CYCLE 13/DAY 1 (n=512) 9.74  (19.64)
CYCLE 14/DAY 1 (n=351) 10.93  (18.67)
CYCLE 15/DAY 1 (n=461) 8.71  (20.53)
CYCLE 16/DAY 1 (n=289) 8.47  (20.66)
CYCLE 17/DAY 1 (n=417) 7.99  (20.80)
CYCLE 18/DAY 1 (n=244) 7.62  (19.86)
CYCLE 19/DAY 1 (n=372) 8.17  (18.92)
CYCLE 20/DAY 1 (n=219) 8.03  (18.45)
CYCLE 21/DAY 1 (n=339) 6.96  (18.71)
CYCLE 22/DAY 1 (n=179) 6.59  (18.97)
CYCLE 23/DAY 1 (n=310) 5.53  (19.50)
CYCLE 24/DAY 1 (n=154) 7.61  (19.58)
CYCLE 25/DAY 1 (n=299) 4.97  (17.98)
CYCLE 26/DAY 1 (n=128) 8.54  (18.97)
CYCLE 27/DAY 1 (n=272) 5.24  (17.61)
CYCLE 28/DAY 1 (n=120) 7.93  (19.53)
CYCLE 29/DAY 1 (n=249) 5.05  (17.07)
CYCLE 30/DAY 1 (n=108) 8.07  (19.95)
End of Treatment (n=450) 0.09  (23.92)
Time Frame Active reporting period is from the time of informed consent until at least 28 days after study treatment last dose. For serious adverse events: those with the possibility of being related to study drug must be reported as minimum thereafter.
Adverse Event Reporting Description All causality (serious and non-serious) AEs
 
Arm/Group Title Crizotinib 250 mg BID
Hide Arm/Group Description 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.
All-Cause Mortality
Crizotinib 250 mg BID
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Crizotinib 250 mg BID
Affected / at Risk (%)
Total   539/1066 (50.56%) 
Blood and lymphatic system disorders   
Anaemia * 1  4/1066 (0.38%) 
Basophilia * 1  1/1066 (0.09%) 
Eosinophilia * 1  1/1066 (0.09%) 
Febrile neutropenia * 1  6/1066 (0.56%) 
Leukocytosis * 1  1/1066 (0.09%) 
Monocytosis * 1  1/1066 (0.09%) 
Thrombocytopenia * 1  1/1066 (0.09%) 
Thrombocytosis * 1  1/1066 (0.09%) 
Cardiac disorders   
Acute myocardial infarction * 1  2/1066 (0.19%) 
Angina pectoris * 1  2/1066 (0.19%) 
Atrial fibrillation * 1  3/1066 (0.28%) 
Bradycardia * 1  1/1066 (0.09%) 
Cardiac arrest * 1  2/1066 (0.19%) 
Cardiac failure * 1  2/1066 (0.19%) 
Cardiac failure congestive * 1  1/1066 (0.09%) 
Cardiac tamponade * 1  1/1066 (0.09%) 
Coronary artery stenosis * 1  1/1066 (0.09%) 
Cyanosis * 1  1/1066 (0.09%) 
Left ventricular failure * 1  1/1066 (0.09%) 
Myocardial infarction * 1  2/1066 (0.19%) 
Myocarditis * 1  1/1066 (0.09%) 
Palpitations * 1  1/1066 (0.09%) 
Pericardial effusion * 1  7/1066 (0.66%) 
Pericarditis * 1  1/1066 (0.09%) 
Supraventricular tachycardia * 1  1/1066 (0.09%) 
Syncope * 1  6/1066 (0.56%) 
Tachycardia * 1  2/1066 (0.19%) 
Angina Unstable * 1  1/1066 (0.09%) 
Eye disorders   
Cataract * 1  2/1066 (0.19%) 
Glaucoma * 1  1/1066 (0.09%) 
Optic atrophy * 1  1/1066 (0.09%) 
Retinal detachment * 1  1/1066 (0.09%) 
Vision blurred * 1  1/1066 (0.09%) 
Vitreous haemorrhage * 1  1/1066 (0.09%) 
Gastrointestinal disorders   
Abdominal pain * 1  6/1066 (0.56%) 
Abdominal wall haematoma * 1  1/1066 (0.09%) 
Ascites * 1  1/1066 (0.09%) 
Colitis * 1  1/1066 (0.09%) 
Constipation * 1  3/1066 (0.28%) 
Diarrhoea * 1  4/1066 (0.38%) 
Diarrhoea haemorrhagic * 1  1/1066 (0.09%) 
Dysphagia * 1  7/1066 (0.66%) 
Gastric ulcer * 1  1/1066 (0.09%) 
Gastritis * 1  1/1066 (0.09%) 
Gastrointestinal haemorrhage * 1  3/1066 (0.28%) 
Ileus * 1  3/1066 (0.28%) 
Intestinal obstruction * 1  1/1066 (0.09%) 
Intestinal perforation * 1  1/1066 (0.09%) 
Nausea * 1  9/1066 (0.84%) 
Oesophageal stenosis * 1  1/1066 (0.09%) 
Oesophagitis * 1  2/1066 (0.19%) 
Pancreatic atrophy * 1  1/1066 (0.09%) 
Pancreatitis * 1  3/1066 (0.28%) 
Pancreatitis acute * 1  1/1066 (0.09%) 
Peptic ulcer haemorrhage * 1  1/1066 (0.09%) 
Peritoneal disorder * 1  1/1066 (0.09%) 
Retroperitoneal haemorrhage * 1  1/1066 (0.09%) 
Small intestinal obstruction * 1  1/1066 (0.09%) 
Subileus * 1  1/1066 (0.09%) 
Upper gastrointestinal haemorrhage * 1  1/1066 (0.09%) 
Vomiting * 1  6/1066 (0.56%) 
Rectal haemorrhage * 1  1/1066 (0.09%) 
General disorders   
Asthenia * 1  7/1066 (0.66%) 
Chest discomfort * 1  2/1066 (0.19%) 
Chest pain * 1  5/1066 (0.47%) 
Chills * 1  1/1066 (0.09%) 
Condition aggravated * 1  2/1066 (0.19%) 
Death * 1  8/1066 (0.75%) 
Device dislocation * 1  1/1066 (0.09%) 
Disease progression * 1  135/1066 (12.66%) 
Fatigue * 1  4/1066 (0.38%) 
Gait disturbance * 1  1/1066 (0.09%) 
General physical health deterioration * 1  9/1066 (0.84%) 
Generalised oedema * 1  3/1066 (0.28%) 
Mass * 1  1/1066 (0.09%) 
Multi-organ failure * 1  1/1066 (0.09%) 
Oedema peripheral * 1  7/1066 (0.66%) 
Pain * 1  1/1066 (0.09%) 
Pyrexia * 1  18/1066 (1.69%) 
Vascular stent thrombosis * 1  1/1066 (0.09%) 
Hepatobiliary disorders   
Cholecystitis * 1  1/1066 (0.09%) 
Drug-induced liver injury * 1  3/1066 (0.28%) 
Hepatic failure * 1  2/1066 (0.19%) 
Hepatitis * 1  1/1066 (0.09%) 
Hepatocellular injury * 1  1/1066 (0.09%) 
Hepatotoxicity * 1  3/1066 (0.28%) 
Immune system disorders   
Contrast media allergy * 1  1/1066 (0.09%) 
Infections and infestations   
Abdominal abscess * 1  1/1066 (0.09%) 
Abscess limb * 1  1/1066 (0.09%) 
Appendicitis * 1  8/1066 (0.75%) 
Bacteraemia * 1  2/1066 (0.19%) 
Bone abscess * 1  1/1066 (0.09%) 
Bronchitis * 1  2/1066 (0.19%) 
Candiduria * 1  1/1066 (0.09%) 
Cellulitis * 1  13/1066 (1.22%) 
Chest wall abscess * 1  1/1066 (0.09%) 
Clostridium difficile infection * 1  1/1066 (0.09%) 
Cystitis * 1  1/1066 (0.09%) 
Diverticulitis * 1  1/1066 (0.09%) 
Empyema * 1  1/1066 (0.09%) 
Gastroenteritis * 1  6/1066 (0.56%) 
Herpes zoster * 1  3/1066 (0.28%) 
Infection * 1  1/1066 (0.09%) 
Infectious pleural effusion * 1  2/1066 (0.19%) 
Infective spondylitis * 1  1/1066 (0.09%) 
Lower respiratory tract infection * 1  3/1066 (0.28%) 
Lung abscess * 1  1/1066 (0.09%) 
Lung infection * 1  14/1066 (1.31%) 
Meningitis * 1  1/1066 (0.09%) 
Metapneumovirus infection * 1  1/1066 (0.09%) 
Oesophageal candidiasis * 1  2/1066 (0.19%) 
Osteomyelitis chronic * 1  1/1066 (0.09%) 
Peritonitis * 1  1/1066 (0.09%) 
Pneumonia * 1  74/1066 (6.94%) 
Pneumonia bacterial * 1  1/1066 (0.09%) 
Pneumonia fungal * 1  1/1066 (0.09%) 
Pneumonia staphylococcal * 1  1/1066 (0.09%) 
Pyelonephritis * 1  1/1066 (0.09%) 
Renal abscess * 1  2/1066 (0.19%) 
Renal cyst infection * 1  2/1066 (0.19%) 
Respiratory tract infection * 1  5/1066 (0.47%) 
Sepsis * 1  8/1066 (0.75%) 
Septic shock * 1  4/1066 (0.38%) 
Skin infection * 1  4/1066 (0.38%) 
Soft tissue infection * 1  1/1066 (0.09%) 
Staphylococcal sepsis * 1  1/1066 (0.09%) 
Upper respiratory tract infection * 1  7/1066 (0.66%) 
Urinary tract infection * 1  7/1066 (0.66%) 
Urinary tract infection bacterial * 1  1/1066 (0.09%) 
Viral infection * 1  1/1066 (0.09%) 
Viral upper respiratory tract infection * 1  1/1066 (0.09%) 
Wound infection * 1  2/1066 (0.19%) 
Lymphangitis * 1  1/1066 (0.09%) 
Injury, poisoning and procedural complications   
Ankle fracture * 1  2/1066 (0.19%) 
Bone fissure * 1  1/1066 (0.09%) 
Dislocation of vertebra * 1  1/1066 (0.09%) 
Fall * 1  6/1066 (0.56%) 
Femoral neck fracture * 1  4/1066 (0.38%) 
Femur fracture * 1  4/1066 (0.38%) 
Hip fracture * 1  1/1066 (0.09%) 
Humerus fracture * 1  1/1066 (0.09%) 
Joint dislocation * 1  1/1066 (0.09%) 
Lower limb fracture * 1  1/1066 (0.09%) 
Overdose * 1  1/1066 (0.09%) 
Pelvic fracture * 1  1/1066 (0.09%) 
Radiation necrosis * 1  1/1066 (0.09%) 
Radiation pneumonitis * 1  1/1066 (0.09%) 
Radius fracture * 1  2/1066 (0.19%) 
Road traffic accident * 1  2/1066 (0.19%) 
Spinal compression fracture * 1  2/1066 (0.19%) 
Subdural haemorrhage * 1  1/1066 (0.09%) 
Traumatic haematoma * 1  1/1066 (0.09%) 
Upper limb fracture * 1  1/1066 (0.09%) 
Craniocerebral injury * 1  1/1066 (0.09%) 
Postoperative wound complication * 1  1/1066 (0.09%) 
Wound dehiscence * 1  1/1066 (0.09%) 
Investigations   
Alanine aminotransferase increased * 1  5/1066 (0.47%) 
Blood albumin decreased * 1  1/1066 (0.09%) 
Blood bilirubin increased * 1  1/1066 (0.09%) 
Blood creatinine increased * 1  1/1066 (0.09%) 
Blood lactate dehydrogenase increased * 1  1/1066 (0.09%) 
C-reactive protein increased * 1  1/1066 (0.09%) 
Electrocardiogram QT prolonged * 1  1/1066 (0.09%) 
Hepatic enzyme increased * 1  1/1066 (0.09%) 
Troponin I increased * 1  1/1066 (0.09%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  3/1066 (0.28%) 
Dehydration * 1  4/1066 (0.38%) 
Failure to thrive * 1  2/1066 (0.19%) 
Fluid retention * 1  1/1066 (0.09%) 
Hypercalcaemia * 1  1/1066 (0.09%) 
Hyperglycaemia * 1  2/1066 (0.19%) 
Hyperkalaemia * 1  1/1066 (0.09%) 
Hypoalbuminaemia * 1  1/1066 (0.09%) 
Hypocalcaemia * 1  1/1066 (0.09%) 
Hypoglycaemia * 1  1/1066 (0.09%) 
Hypokalaemia * 1  5/1066 (0.47%) 
Hypomagnesaemia * 1  1/1066 (0.09%) 
Hyponatraemia * 1  4/1066 (0.38%) 
Hypophosphataemia * 1  1/1066 (0.09%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  2/1066 (0.19%) 
Back pain * 1  5/1066 (0.47%) 
Bursitis * 1  1/1066 (0.09%) 
Chest wall mass * 1  1/1066 (0.09%) 
Joint swelling * 1  1/1066 (0.09%) 
Lumbar spinal stenosis * 1  1/1066 (0.09%) 
Muscular weakness * 1  2/1066 (0.19%) 
Musculoskeletal pain * 1  3/1066 (0.28%) 
Myalgia * 1  1/1066 (0.09%) 
Myopathy * 1  1/1066 (0.09%) 
Neck pain * 1  2/1066 (0.19%) 
Osteoarthritis * 1  1/1066 (0.09%) 
Pain in extremity * 1  2/1066 (0.19%) 
Pathological fracture * 1  5/1066 (0.47%) 
Spinal column stenosis * 1  1/1066 (0.09%) 
Spondylolisthesis * 1  1/1066 (0.09%) 
Systemic lupus erythematosus * 1  1/1066 (0.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Basal cell carcinoma * 1  1/1066 (0.09%) 
Breast cancer * 1  1/1066 (0.09%) 
Gallbladder cancer * 1  1/1066 (0.09%) 
Malignant melanoma * 1  2/1066 (0.19%) 
Metastases to meninges * 1  1/1066 (0.09%) 
Neoplasm malignant * 1  1/1066 (0.09%) 
Neuroendocrine tumour * 1  1/1066 (0.09%) 
Plasma cell myeloma * 1  1/1066 (0.09%) 
Prostate cancer * 1  1/1066 (0.09%) 
Small cell lung cancer * 1  1/1066 (0.09%) 
Squamous cell carcinoma of skin * 1  2/1066 (0.19%) 
Nervous system disorders   
Aphasia * 1  2/1066 (0.19%) 
Ataxia * 1  1/1066 (0.09%) 
Brain oedema * 1  3/1066 (0.28%) 
Cerebellar infarction * 1  1/1066 (0.09%) 
Cerebral haemorrhage * 1  4/1066 (0.38%) 
Cerebral infarction * 1  1/1066 (0.09%) 
Cerebrovascular accident * 1  1/1066 (0.09%) 
Chorea * 1  1/1066 (0.09%) 
Coma * 1  1/1066 (0.09%) 
Depressed level of consciousness * 1  1/1066 (0.09%) 
Dizziness * 1  2/1066 (0.19%) 
Dysarthria * 1  2/1066 (0.19%) 
Generalised tonic-clonic seizure * 1  1/1066 (0.09%) 
Haemorrhage intracranial * 1  1/1066 (0.09%) 
Headache * 1  4/1066 (0.38%) 
Intracranial pressure increased * 1  1/1066 (0.09%) 
Ischaemic stroke * 1  1/1066 (0.09%) 
Nervous system disorder * 1  2/1066 (0.19%) 
Neurological decompensation * 1  1/1066 (0.09%) 
Paraplegia * 1  1/1066 (0.09%) 
Peripheral motor neuropathy * 1  1/1066 (0.09%) 
Peripheral sensorimotor neuropathy * 1  1/1066 (0.09%) 
Peripheral sensory neuropathy * 1  1/1066 (0.09%) 
Pyramidal tract syndrome * 1  1/1066 (0.09%) 
Seizure * 1  9/1066 (0.84%) 
Spinal cord compression * 1  2/1066 (0.19%) 
Transient ischaemic attack * 1  3/1066 (0.28%) 
Tremor * 1  1/1066 (0.09%) 
Vocal cord paralysis * 1  2/1066 (0.19%) 
Psychiatric disorders   
Completed suicide * 1  1/1066 (0.09%) 
Confusional state * 1  7/1066 (0.66%) 
Depression * 1  3/1066 (0.28%) 
Disorientation * 1  1/1066 (0.09%) 
Mania * 1  1/1066 (0.09%) 
Mental status changes * 1  2/1066 (0.19%) 
Suicide attempt * 1  1/1066 (0.09%) 
Renal and urinary disorders   
Acute kidney injury * 1  5/1066 (0.47%) 
Dysuria * 1  2/1066 (0.19%) 
Haematuria * 1  1/1066 (0.09%) 
Hydronephrosis * 1  2/1066 (0.19%) 
Nephrolithiasis * 1  2/1066 (0.19%) 
Renal cyst * 1  13/1066 (1.22%) 
Renal cyst haemorrhage * 1  1/1066 (0.09%) 
Renal failure * 1  1/1066 (0.09%) 
Ureteral polyp * 1  1/1066 (0.09%) 
Urinary retention * 1  2/1066 (0.19%) 
Urinary tract obstruction * 1  1/1066 (0.09%) 
Reproductive system and breast disorders   
Benign prostatic hyperplasia * 1  1/1066 (0.09%) 
Pelvic pain * 1  1/1066 (0.09%) 
Respiratory, thoracic and mediastinal disorders   
Acute respiratory distress syndrome * 1  1/1066 (0.09%) 
Acute respiratory failure * 1  3/1066 (0.28%) 
Alveolitis * 1  1/1066 (0.09%) 
Asphyxia * 1  1/1066 (0.09%) 
Atelectasis * 1  1/1066 (0.09%) 
Bronchial hyperreactivity * 1  1/1066 (0.09%) 
Chronic obstructive pulmonary disease * 1  1/1066 (0.09%) 
Cough * 1  3/1066 (0.28%) 
Dyspnoea * 1  39/1066 (3.66%) 
Epistaxis * 1  1/1066 (0.09%) 
Haemoptysis * 1  3/1066 (0.28%) 
Hypoxia * 1  4/1066 (0.38%) 
Interstitial lung disease * 1  5/1066 (0.47%) 
Lung infiltration * 1  1/1066 (0.09%) 
Oropharyngeal pain * 1  1/1066 (0.09%) 
Pleural effusion * 1  14/1066 (1.31%) 
Pleuritic pain * 1  1/1066 (0.09%) 
Pneumonia aspiration * 1  4/1066 (0.38%) 
Pneumonitis * 1  17/1066 (1.59%) 
Pneumothorax * 1  8/1066 (0.75%) 
Pulmonary arterial hypertension * 1  1/1066 (0.09%) 
Pulmonary artery thrombosis * 1  2/1066 (0.19%) 
Pulmonary embolism * 1  26/1066 (2.44%) 
Pulmonary haemorrhage * 1  1/1066 (0.09%) 
Pulmonary oedema * 1  1/1066 (0.09%) 
Pulmonary thrombosis * 1  1/1066 (0.09%) 
Rales * 1  2/1066 (0.19%) 
Respiratory failure * 1  17/1066 (1.59%) 
Haemothorax * 1  1/1066 (0.09%) 
Skin and subcutaneous tissue disorders   
Paraneoplastic pemphigus * 1  1/1066 (0.09%) 
Rash * 1  1/1066 (0.09%) 
Surgical and medical procedures   
Pleural decortication * 1  1/1066 (0.09%) 
Vascular disorders   
Deep vein thrombosis * 1  14/1066 (1.31%) 
Embolism * 1  1/1066 (0.09%) 
Haematoma * 1  3/1066 (0.28%) 
Hypotension * 1  1/1066 (0.09%) 
Hypovolaemic shock * 1  1/1066 (0.09%) 
Orthostatic hypotension * 1  1/1066 (0.09%) 
Peripheral arterial occlusive disease * 1  1/1066 (0.09%) 
Peripheral embolism * 1  2/1066 (0.19%) 
Phlebitis * 1  1/1066 (0.09%) 
Superior vena cava syndrome * 1  4/1066 (0.38%) 
Thrombophlebitis * 1  1/1066 (0.09%) 
Thrombosis * 1  5/1066 (0.47%) 
Vasculitis * 1  1/1066 (0.09%) 
Vena cava thrombosis * 1  2/1066 (0.19%) 
Venous thrombosis * 1  4/1066 (0.38%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (v18.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Crizotinib 250 mg BID
Affected / at Risk (%)
Total   1038/1066 (97.37%) 
Blood and lymphatic system disorders   
Anaemia * 1  138/1066 (12.95%) 
Leukopenia * 1  101/1066 (9.47%) 
Lymphopenia * 1  71/1066 (6.66%) 
Neutropenia * 1  180/1066 (16.89%) 
Cardiac disorders   
Bradycardia * 1  93/1006 (9.24%) 
Eye disorders   
Photopsia * 1  96/1066 (9.01%) 
Vision blurred * 1  80/1066 (7.50%) 
Visual impairment * 1  460/1066 (43.15%) 
Gastrointestinal disorders   
Abdominal pain * 1  118/1066 (11.07%) 
Abdominal pain upper * 1  106/1066 (9.94%) 
Constipation * 1  475/1066 (44.56%) 
Diarrhoea * 1  548/1066 (51.41%) 
Dyspepsia * 1  81/1066 (7.60%) 
Dysphagia * 1  56/1066 (5.25%) 
Nausea * 1  603/1066 (56.57%) 
Vomiting * 1  565/1066 (53.00%) 
General disorders   
Asthenia * 1  156/1066 (14.63%) 
Chest pain * 1  105/1066 (9.85%) 
Fatigue * 1  326/1066 (30.58%) 
Oedema * 1  96/1066 (9.01%) 
Oedema peripheral * 1  450/1066 (42.21%) 
Pyrexia * 1  181/1066 (16.98%) 
Infections and infestations   
Nasopharyngitis * 1  113/1066 (10.60%) 
Upper respiratory tract infection * 1  145/1066 (13.60%) 
Urinary tract infection * 1  62/1066 (5.82%) 
Injury, poisoning and procedural complications   
Fall * 1  59/1066 (5.53%) 
Investigations   
Alanine aminotransferase increased * 1  302/1006 (30.02%) 
Aspartate aminotransferase increased * 1  233/1006 (23.16%) 
Blood alkaline phosphatase increased * 1  76/1006 (7.55%) 
Blood creatinine increased * 1  105/1006 (10.44%) 
Blood lactate dehydrogenase increased * 1  60/1006 (5.96%) 
Neutrophil count decreased * 1  84/1066 (7.88%) 
Weight decreased * 1  109/1066 (10.23%) 
Weight increased * 1  98/1066 (9.19%) 
White blood cell count decreased * 1  98/1006 (9.74%) 
Metabolism and nutrition disorders   
Decreased appetite * 1  326/1066 (30.58%) 
Hyperglycaemia * 1  55/1066 (5.16%) 
Hypoalbuminaemia * 1  98/1066 (9.19%) 
Hypocalcaemia * 1  99/1066 (9.29%) 
Hypokalaemia * 1  77/1066 (7.22%) 
Hyponatraemia * 1  54/1066 (5.07%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  131/1066 (12.29%) 
Back pain * 1  184/1066 (17.26%) 
Muscle spasms * 1  79/1066 (7.41%) 
Muscular weakness * 1  57/1066 (5.35%) 
Pain in extremity * 1  137/1066 (12.85%) 
Musculoskeletal pain * 1  74/1066 (6.94%) 
Nervous system disorders   
Dizziness * 1  265/1066 (24.86%) 
Dysgeusia * 1  213/1066 (19.98%) 
Headache * 1  214/1066 (20.08%) 
Hypoaesthesia * 1  65/1066 (6.10%) 
Paraesthesia * 1  83/1066 (7.79%) 
Psychiatric disorders   
Anxiety * 1  76/1066 (7.13%) 
Insomnia * 1  136/1066 (12.76%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  260/1066 (24.39%) 
Dyspnoea * 1  224/1066 (21.01%) 
Haemoptysis * 1  55/1066 (5.16%) 
Oropharyngeal pain * 1  75/1066 (7.04%) 
Productive cough * 1  71/1066 (6.66%) 
Skin and subcutaneous tissue disorders   
Alopecia * 1  67/1066 (6.29%) 
Pruritus * 1  84/1066 (7.88%) 
Rash * 1  134/1066 (12.57%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (v18.1)
Pharmacogenetic analysis of renal adverse events was not performed as no gene alleles have been identified in published literature with statistically significant association with renal toxicity to support a case control association analysis.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00932451    
Other Study ID Numbers: A8081005
2009-012504-13 ( EudraCT Number )
First Submitted: June 30, 2009
First Posted: July 3, 2009
Results First Submitted: March 14, 2016
Results First Posted: June 9, 2016
Last Update Posted: January 13, 2017