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

• ClinicalTrials.gov Identifier: NCT00932893
• Recruitment Status: Completed
• First Posted: July 3, 2009
• Results First Posted: June 6, 2013
• Last Update Posted: January 2, 2017
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: PF-02341066; Drug: Pemetrexed; Drug: Docetaxel
• Enrollment: 347

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg per square meter (mg/m^2) intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Period Title: Overall Study
Started	173	174
Treated	172	171
Completed	40	4
Not Completed	133	170
Reason Not Completed
Death	115	24
Lost to Follow-up	8	0
Withdrawal by Subject	5	2
Other	5	144

Baseline Characteristics

Arm/Group Title		Crizotinib	Chemotherapy	Total
Arm/Group Description		Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Total of all reporting groups
Overall Number of Baseline Participants		173	174	347
Baseline Analysis Population Description		Full analysis set (FAS) included all participants who were randomized to study treatment.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	173 participants	174 participants	347 participants
		50.3 (13.1)	49.8 (13.0)	50.0 (13.0)
Gender; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	173 participants	174 participants	347 participants
	Female	98 56.6%	95 54.6%	193 55.6%
	Male	75 43.4%	79 45.4%	154 44.4%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS: Time in months from randomization to first documentation of objective disease progression as determined by independent radiology review or to death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria version 1.1 (RECIST v1.1), as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time Frame	Randomization until progressive disease (PD) or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all participants who were randomized to study treatment.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	173	174
Median (95% Confidence Interval); Unit of Measure: months
	7.7; (6.0 to 8.8)	3.0; (2.6 to 4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib, Chemotherapy
	Comments	P-value was obtained from 1-sided log-rank test stratified by Eastern Cooperative Oncology Group performance status (ECOG PS) score, brain metastases, and prior epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) treatment. The hazard ratio and corresponding 95% confidence interval (CI) from the stratified Cox Proportional Hazards model were also presented.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	To control family-wise Type 1 error, a step-down procedure was applied in following order: PFS, objective response rate (ORR), overall survival (OS), and disease control rate (DCR). Statistical significance: 1-sided at alpha=0.025.
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.487
	Confidence Interval	95%; 0.371 to 0.638
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS: Time in months from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 30.4.
Time Frame	Randomization until death (up to 4.5 years)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	173	174
Median (95% Confidence Interval); Unit of Measure: months
	21.7; (18.9 to 30.5)	21.9; (16.8 to 26.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib, Chemotherapy
	Comments	P-value was obtained from 1-sided log-rank test stratified by ECOG PS score, brain metastases, and prior EGFR TKI treatment. The hazard ratio and corresponding 95% CI from the stratified Cox proportional hazards model were also presented.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1145
	Comments	Statistical significance: 1-sided at alpha=0.025
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.854
	Confidence Interval	95%; 0.661 to 1.104
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Survival Probability at Months 6 and 12
Description	Overall survival probability at Month 6 and 12 was defined as the probability of survival at 6 and 12 months respectively, after the randomization of study treatment. The survival probability was estimated using the Kaplan-Meier method.
Time Frame	Month 6, 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	173	174
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percent chance of survival
Month 6	86.6; (80.5 to 90.9)	83.8; (77.4 to 88.5)
Month 12	70.4; (62.9 to 76.7)	66.7; (59.1 to 73.2)

4. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis). PR: at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Objective response is based on independent radiology review.
Time Frame	Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	173	174
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	65.3; (57.7 to 72.4)	19.5; (13.9 to 26.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib, Chemotherapy
	Comments	P-value was obtained from Cochran-Mantel-Haenszel (CMH) test stratified by ECOG PS, brain metastases, and prior EGFR TKI treatment. The risk ratio and corresponding 95% CI from the stratified CMH test were also reported.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Statistical significance: 2-sided at alpha=0.025.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	3.394
	Confidence Interval	95%; 2.463 to 4.676
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Percentage of Participants With Disease Control at Week 6
Description	Disease control: participants with CR, PR, or stable disease (SD) according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. Disease control is based on independent radiology review.
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	173	174
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	81.5; (74.9 to 87.0)	55.2; (47.5 to 62.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib, Chemotherapy
	Comments	P-value was obtained from CMH test stratified by ECOG PS, brain metastases, and prior EGFR TKI treatment. The risk ratio and corresponding 95% CI from the stratified CMH test were also reported.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Statistical significance: 2-sided at alpha=0.0004.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.502
	Confidence Interval	95%; 1.297 to 1.741
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants With Disease Control at Week 12
Description	Disease control: participants with CR, PR, or SD according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	173	174
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	64.2; (56.5 to 71.3)	38.5; (31.2 to 46.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib, Chemotherapy
	Comments	P-value was obtained from CMH test stratified by ECOG PS, brain metastases, and prior EGFR TKI treatment. The risk ratio and corresponding 95% CI from the stratified CMH test were also reported.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Statistical significance: 2-sided at alpha=0.0004.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.697
	Confidence Interval	(2-Sided) 95%; 1.368 to 2.103
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7.02. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame	Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment. Here 'N' (number of participant analyzed) signifies participants with objective tumor response.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	113	34
Median (95% Confidence Interval); Unit of Measure: weeks
	32.1; (26.4 to 42.3)	24.4; (15 to 36)

8. Secondary Outcome

Title	Time to Tumor Response (TTR)
Description	Time from date of randomization to first documentation of objective tumor response. TTR was calculated for the subgroup of participants with objective tumor response. Objective tumor response was defined as CR or PR according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least 30 % decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
Time Frame	Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment. Here 'N' (number of participant analyzed) signifies participants with objective tumor response.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	113	34
Median (Full Range); Unit of Measure: weeks
	6.3; (4.4 to 48.4)	12.6; (5 to 37.1)

9. Secondary Outcome

Title	Plasma Concentration of Crizotinib
Description	Only participants receiving crizotinib were to be analyzed for this outcome measure as per planned analysis.
Time Frame	Pre-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of Cycles 2, 3, 5

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis population included all randomized participants who received at least 1 dose of study treatment and had 1 of the PK parameters of interest. Here "N" (number of participants analyzed) signifies participants evaluable for this measure. n=participants evaluable at specific time points.

Arm/Group Title	Crizotinib
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	152
Geometric Mean (Standard Deviation); Unit of Measure: nanogram per milliliter (ng/mL)
Cycle 1 Day 1 (n=15)	NA [1] (NA)
Cycle 1 Day 15 (n=92)	298 (148)
Cycle 2 Day 1 (n=62)	293 (154)
Cycle 3 Day 1 (n=61)	306 (135)
Cycle 5 Day 1 (n=47)	291 (156)

[1]

Data was not summarized since none of the participants had Ctrough values above lower limit of quantification (LLOQ).

10. Secondary Outcome

Title	Number of Participants With Categorical Maximum QTcF for Crizotinib
Description	QT interval corrected using Fridericia's formula (QTcF): QT interval (time corresponding to the beginning of depolarization to re-polarization of the ventricles) divided by cube root of RR interval. Maximum QTcF was categorized as less than (<) 450 milliseconds (msec), 450 msec to <480 msec, 480 msec to <500 msec, and more than or equal to (>=) 500 msec. A participant is reported only once under the maximum QTcF interval observed at any of the time-points. Only participants receiving crizotinib were to be analyzed for this outcome measure as per planned analysis.
Time Frame	Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 1, 2

Outcome Measure Data

Analysis Population Description

ECG-evaluable population included all randomized participants who received at least 1 dose of study treatment, and had a baseline and at least 1 post-baseline ECG measurement.

Arm/Group Title	Crizotinib
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	155
Measure Type: Number; Unit of Measure: participants
<450 msec	137
450 msec to <480 msec	9
480 msec to <500 msec	1
>=500 msec	8

11. Secondary Outcome

Title	Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins
Description	Descriptive statistics (absolute value and change from baseline as measured by ratio to baseline) for each best overall response category (CR, PR, SD, PD or combined) have been used to summarize the data from optional soluble c-Met ectodomain assays for crizotinib treated patients.
Time Frame	Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 2, end of treatment (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

The soluble biomarker-evaluable population includes patients from the SA population that received PF-02341066, who have an optional blood sample prior to dosing on Cycle 1 Day 1 and have at least 1 on-treatment soluble biomarker evaluation (Cycle 2 Day 1 and/or end of treatment).

Arm/Group Title	Overall Values
Arm/Group Description:	Overall assessment for complete response, partial response, stable disease, progressive disease and early death
Overall Number of Participants Analyzed	172
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter (ng/mL)
Baseline (N = 81)	1428.3 (363.9)
Cycle 2 Day 1 6-hour post dose (N = 69)	1683.0 (325.6)
End of treatment (N = 40)	1751.8 (327.9)

12. Secondary Outcome

Title	Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough
Description	TTD in pain (pain in chest from European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer [EORTC QLQ-LC13]), dyspnea (from EORTC QLQ-LC13), or cough (from EORTC QLQ-LC13) symptoms was defined as the time from randomization to the earliest time the participant's score showed a 10 point or higher increase from baseline in any of the three symptoms from the instrument. The transformed score of pain, dyspnea, and cough symptom scales of EORTC QLQ-LC13 range from 0 to 100, greater scores = higher symptom severity.
Time Frame	Baseline up to end of treatment (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

Patient Reported Outcome (PRO) evaluable population included all randomized participants who received at least 1 dose of study treatment, and had a baseline and at least 1 post-baseline PRO assessment.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	162	151
Median (95% Confidence Interval); Unit of Measure: months
	4.5; (3.0 to 6.9)	1.4; (1.0 to 1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib, Chemotherapy
	Comments	The p-value was obtained from 2-sided unstratified log-rank test. The hazard ratio and corresponding 95% CI from the Cox Proportional Hazards model were also presented.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.497
	Confidence Interval	95%; 0.373 to 0.661
	Estimation Comments	[Not Specified]

13. Secondary Outcome

Title	European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Description	EORTC QLQ-C30: included global health status/quality of life (QoL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score for Global Qol/functional scales=better level of QoL/functioning or higher score for symptom scale=greater degree of symptoms.
Time Frame	Baseline, Day (D) 1 of each cycle (C) until disease progression, end of treatment (EOT, up to 112 weeks)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for specified time points for each arm group, respectively.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	165	163
Mean (Standard Deviation); Unit of Measure: units on a scale
Global QoL: Baseline (n=165, 162)	57.2 (21.5)	58.1 (22.2)
Global QoL: C2D1 (n=154, 133)	64.5 (21.8)	58.1 (23.1)
Global QoL: C3D1 (n=154, 106)	65.2 (22.1)	59.4 (23.1)
Global QoL: C4D1 (n=135, 90)	68.4 (19.6)	61.1 (20.8)
Global QoL: C5D1 (n=123, 74)	68.5 (20.2)	64.1 (22.7)
Global QoL: C6D1 (n=120, 70)	68.3 (19.8)	67.5 (23.5)
Global QoL: C7D1 (n=114, 52)	69.5 (19.3)	66.5 (23.1)
Global QoL: C8D1 (n=110, 43)	68.7 (20.1)	66.9 (25.3)
Global QoL: C9D1 (n=101, 37)	68.7 (21.0)	66.4 (27.8)
Global QoL: C10D1 (n=94, 33)	67.0 (21.6)	67.4 (26.8)
Global QoL: C11D1 (n=83, 25)	69.5 (20.2)	71.0 (21.8)
Global QoL: C12D1 (n=76, 23)	67.9 (22.0)	65.6 (24.1)
Global QoL: C13D1 (n=74, 21)	66.8 (23.6)	66.7 (23.6)
Global QoL: C14D1 (n=66, 19)	71.5 (20.0)	65.8 (23.4)
Global QoL: C15D1 (n=62, 16)	69.0 (22.2)	66.1 (24.1)
Global QoL: C16D1 (n=53, 12)	69.7 (18.1)	63.2 (25.5)
Global QoL: C17D1 (n=47, 11)	67.6 (20.5)	69.7 (23.4)
Global QoL: C18D1 (n=44, 11)	65.7 (19.9)	70.5 (22.5)
Global QoL: C19D1 (n=40, 9)	69.2 (19.2)	72.2 (20.0)
Global QoL: C20D1 (n=35, 8)	64.3 (20.6)	60.4 (21.2)
Global QoL: C21D1 (n=30, 8)	65.0 (18.4)	63.5 (23.5)
Global QoL: C22D1 (n=24, 7)	70.8 (19.3)	64.3 (24.9)
Global QoL: C23D1 (n=23, 4)	67.0 (22.5)	50.0 (19.2)
Global QoL: C24D1 (n=20, 3)	67.1 (18.8)	55.6 (19.2)
Global QoL: C25D1 (n=18, 3)	67.1 (17.7)	61.1 (19.2)
Global QoL: C26D1 (n=14, 3)	60.7 (22.0)	55.6 (12.7)
Global QoL: C27D1 (n=14, 2)	58.9 (20.3)	41.7 (0.0)
Global QoL: C28D1 (n=11, 2)	66.7 (18.3)	54.2 (17.7)
Global QoL: C29D1 (n=8, 2)	59.4 (18.6)	41.7 (11.8)
Global QoL: C30D1 (n=8, 1)	64.6 (19.3)	33.3 [1] (NA)
Global QoL: C31D1 (n=7, 0)	64.3 (17.2)	NA [2] (NA)
Global QoL: C32D1 (n=6, 0)	59.7 (17.0)	NA [2] (NA)
Global QoL: C33D1 (n=6, 0)	66.7 (18.3)	NA [2] (NA)
Global QoL: C34D1 (n=5, 0)	68.3 (14.9)	NA [2] (NA)
Global QoL: C35D1 (n=4, 0)	60.4 (22.9)	NA [2] (NA)
Global QoL: C36D1 (n=1, 0)	66.7 [1] (NA)	NA [2] (NA)
Global QoL: C37D1 (n=1, 0)	66.7 [1] (NA)	NA [2] (NA)
Physical Functioning: Baseline (n=165, 163)	76.3 (20.7)	75.8 (21.9)
Physical Functioning: C2D1 (n=155, 133)	79.2 (20.9)	73.5 (22.3)
Physical Functioning: C3D1 (n=154, 106)	82.3 (18.1)	75.5 (20.2)
Physical Functioning: C4D1 (n=135, 91)	83.8 (16.2)	76.6 (20.2)
Physical Functioning: C5D1 (n=123, 74)	84.5 (16.2)	78.6 (23.0)
Physical Functioning: C6D1 (n=120, 70)	86.2 (16.7)	80.7 (19.7)
Physical Functioning: C7D1 (n=115, 52)	86.7 (15.0)	80.3 (19.7)
Physical Functioning: C8D1 (n=111, 43)	86.5 (16.3)	81.6 (18.5)
Physical Functioning: C9D1 (n=101, 37)	87.7 (14.2)	82.3 (19.1)
Physical Functioning: C10D1 (n=94, 33)	87.9 (14.8)	81.8 (20.7)
Physical Functioning: C11D1 (n=84, 25)	87.2 (16.7)	83.2 (19.0)
Physical Functioning: C12D1 (n=76, 23)	88.1 (15.3)	79.7 (22.8)
Physical Functioning: C13D1 (n=74, 21)	89.3 (13.9)	78.4 (23.6)
Physical Functioning: C14D1 (n=66, 19)	89.0 (14.3)	80.0 (21.4)
Physical Functioning: C15D1 (n=62, 16)	87.8 (15.3)	82.9 (15.4)
Physical Functioning: C16D1 (n=53, 12)	89.3 (11.5)	81.1 (19.5)
Physical Functioning: C17D1 (n=47, 11)	86.6 (16.8)	81.8 (15.8)
Physical Functioning: C18D1 (n=45, 11)	88.4 (13.3)	82.4 (16.1)
Physical Functioning: C19D1 (n=40, 9)	88.3 (12.4)	81.5 (12.8)
Physical Functioning: C20D1 (n=35, 8)	87.6 (12.7)	79.2 (17.3)
Physical Functioning: C21D1 (n=30, 8)	88.4 (10.9)	77.5 (22.5)
Physical Functioning: C22D1 (n=24, 7)	90.6 (8.3)	78.1 (24.3)
Physical Functioning: C23D1 (n=23, 4)	88.0 (13.1)	60.0 (27.2)
Physical Functioning: C24D1 (n=20, 3)	85.0 (14.0)	64.4 (32.9)
Physical Functioning: C25D1 (n=18, 3)	87.4 (11.6)	60.0 (29.1)
Physical Functioning: C26D1 (n=14, 3)	80.5 (25.3)	62.2 (30.8)
Physical Functioning: C27D1 (n=14, 2)	78.6 (27.8)	50.0 (23.6)
Physical Functioning: C28D1 (n=11, 2)	81.8 (24.1)	60.0 (18.9)
Physical Functioning: C29D1 (n=8, 2)	85.0 (15.0)	46.7 (28.3)
Physical Functioning: C30D1 (n=8, 1)	82.5 (21.4)	26.7 [1] (NA)
Physical Functioning: C31D1 (n=7, 0)	83.8 (17.2)	NA [2] (NA)
Physical Functioning: C32D1 (n=6, 0)	88.9 (9.1)	NA [2] (NA)
Physical Functioning: C33D1 (n=6, 0)	90.0 (7.0)	NA [2] (NA)
Physical Functioning: C34D1 (n=5, 0)	85.3 (7.3)	NA [2] (NA)
Physical Functioning: C35D1 (n=4, 0)	91.7 (3.3)	NA [2] (NA)
Physical Functioning: C36D1 (n=1, 0)	86.7 [1] (NA)	NA [2] (NA)
Physical Functioning: C37D1 (n=1, 0)	86.7 [1] (NA)	NA [2] (NA)
Role Functioning: Baseline (n=165, 163)	69.3 (28.7)	66.6 (30.2)
Role Functioning: C2D1 (n=155, 133)	73.8 (28.9)	64.7 (29.7)
Role Functioning: C3D1 (n=154, 106)	74.4 (28.6)	65.3 (27.7)
Role Functioning: C4D1 (n=134, 91)	77.9 (25.7)	67.2 (27.3)
Role Functioning: C5D1 (n=123, 74)	78.2 (24.3)	69.6 (27.4)
Role Functioning: C6D1 (n=120, 70)	80.0 (24.1)	69.5 (26.2)
Role Functioning: C7D1 (n=115, 52)	81.7 (22.6)	72.1 (25.9)
Role Functioning: C8D1 (n=111, 43)	80.4 (23.9)	75.2 (28.3)
Role Functioning: C9D1 (n=101, 37)	80.9 (25.8)	76.6 (27.6)
Role Functioning: C10D1 (n=94, 33)	81.6 (23.1)	75.3 (28.3)
Role Functioning: C11D1 (n=84, 25)	81.3 (23.8)	75.3 (25.5)
Role Functioning: C12D1 (n=76, 23)	81.6 (23.2)	72.5 (29.6)
Role Functioning: C13D1 (n=74, 21)	80.2 (25.5)	68.3 (32.0)
Role Functioning: C14D1 (n=66, 19)	83.8 (21.3)	68.4 (30.4)
Role Functioning: C15D1 (n=62, 16)	80.6 (24.0)	77.1 (27.8)
Role Functioning: C16D1 (n=53, 12)	84.0 (19.0)	69.4 (34.0)
Role Functioning: C17D1 (n=47, 11)	77.7 (25.4)	71.2 (38.1)
Role Functioning: C18D1 (n=45, 11)	80.0 (22.4)	71.2 (31.7)
Role Functioning: C19D1 (n=40, 9)	82.1 (19.4)	74.1 (29.0)
Role Functioning: C20D1 (n=35, 8)	81.9 (17.8)	70.8 (36.5)
Role Functioning: C21D1 (n=30, 8)	80.0 (24.1)	66.7 (32.1)
Role Functioning: C22D1 (n=24, 7)	84.7 (19.0)	67.9 (33.5)
Role Functioning: C23D1 (n=23, 4)	76.8 (26.9)	37.5 (25.0)
Role Functioning: C24D1 (n=20, 3)	80.8 (24.3)	44.4 (38.5)
Role Functioning: C25D1 (n=18, 3)	87.0 (19.4)	44.4 (25.5)
Role Functioning: C26D1 (n=14, 3)	75.0 (29.1)	33.3 (33.3)
Role Functioning: C27D1 (n=14, 2)	69.0 (35.1)	25.0 (11.8)
Role Functioning: C28D1 (n=11, 2)	77.3 (33.6)	25.0 (35.4)
Role Functioning: C29D1 (n=8, 2)	77.1 (34.4)	25.0 (11.8)
Role Functioning: C30D1 (n=8, 1)	77.1 (34.4)	0.0 [1] (NA)
Role Functioning: C31D1 (n=7, 0)	71.4 (36.9)	NA [2] (NA)
Role Functioning: C32D1 (n=6, 0)	86.1 (12.5)	NA [2] (NA)
Role Functioning: C33D1 (n=6, 0)	88.9 (13.6)	NA [2] (NA)
Role Functioning: C34D1 (n=5, 0)	96.7 (7.5)	NA [2] (NA)
Role Functioning: C35D1 (n=4, 0)	91.7 (16.7)	NA [2] (NA)
Role Functioning: C36D1 (n=1, 0)	100.0 [1] (NA)	NA [2] (NA)
Role Functioning: C37D1 (n=1, 0)	100.0 [1] (NA)	NA [2] (NA)
Emotional Functioning: Baseline (n=165, 162)	74.5 (21.3)	73.7 (20.7)
Emotional Functioning: C2D1 (n=155, 133)	83.1 (18.7)	77.7 (19.3)
Emotional Functioning: C3D1 (n=154, 106)	83.3 (16.7)	77.9 (21.5)
Emotional Functioning: C4D1 (n=135, 90)	84.1 (17.3)	80.5 (18.9)
Emotional Functioning: C5D1 (n=123, 74)	83.0 (19.1)	79.8 (19.9)
Emotional Functioning: C6D1 (n=120, 70)	85.3 (17.8)	81.2 (19.4)
Emotional Functioning: C7D1 (n=115, 52)	86.4 (16.5)	81.9 (17.6)
Emotional Functioning: C8D1 (n=111, 43)	83.9 (19.8)	81.6 (20.7)
Emotional Functioning: C9D1 (n=101, 37)	84.4 (19.0)	82.4 (19.6)
Emotional Functioning: C10D1 (n=94, 33)	87.2 (16.8)	81.8 (21.2)
Emotional Functioning: C11D1 (n=84,25)	86.1 (16.7)	85.0 (17.8)
Emotional Functioning: C12D1 (n=76, 23)	85.3 (18.6)	84.8 (18.6)
Emotional Functioning: C13D1 (n=74, 21)	84.9 (19.0)	80.6 (19.1)
Emotional Functioning: C14D1 (n=66, 19)	84.5 (19.9)	81.6 (21.1)
Emotional Functioning: C15D1 (n=62, 16)	86.3 (18.0)	82.3 (18.2)
Emotional Functioning: C16D1 (n=53, 12)	85.8 (17.6)	77.8 (27.8)
Emotional Functioning: C17D1 (n=47, 11)	85.6 (22.0)	79.5 (23.4)
Emotional Functioning: C18D1 (n=44, 11)	86.4 (17.2)	75.8 (27.8)
Emotional Functioning: C19D1 (n=40, 9)	87.3 (16.0)	81.5 (20.7)
Emotional Functioning: C20D1 (n=35, 8)	83.8 (17.5)	82.3 (25.0)
Emotional Functioning: C21D1 (n=30, 8)	84.5 (17.1)	80.2 (29.5)
Emotional Functioning: C22D1 (n=24, 7)	83.7 (21.6)	78.6 (24.9)
Emotional Functioning: C23D1 (n=23, 4)	84.1 (19.8)	70.8 (21.0)
Emotional Functioning: C24D1 (n=20, 3)	87.9 (16.1)	66.7 (30.0)
Emotional Functioning: C25D1 (n=18, 3)	81.5 (19.5)	72.2 (24.1)
Emotional Functioning: C26D1 (n=14, 3)	73.2 (28.3)	72.2 (24.1)
Emotional Functioning: C27D1 (n=14, 2)	70.8 (27.3)	58.3 (0.0)
Emotional Functioning: C28D1 (n=11, 2)	81.1 (27.2)	58.3 (0.0)
Emotional Functioning: C29D1 (n=8, 2)	86.5 (15.4)	54.2 (5.9)
Emotional Functioning: C30D1 (n=8, 1)	84.4 (25.0)	58.3 [1] (NA)
Emotional Functioning: C31D1 (n=7, 0)	76.2 (28.2)	NA [2] (NA)
Emotional Functioning: C32D1 (n=6, 0)	87.5 (17.3)	NA [2] (NA)
Emotional Functioning: C33D1 (n=6, 0)	90.3 (13.4)	NA [2] (NA)
Emotional Functioning: C34D1 (n=5, 0)	91.7 (14.4)	NA [2] (NA)
Emotional Functioning: C35D1 (n=4, 0)	83.3 (20.4)	NA [2] (NA)
Emotional Functioning: C36D1 (n=1, 0)	58.3 [1] (NA)	NA [2] (NA)
Emotional Functioning: C37D1 (n=1, 0)	58.3 [1] (NA)	NA [2] (NA)
Cognitive Functioning: Baseline (n=165, 162)	85.6 (18.3)	83.6 (22.3)
Cognitive Functioning: C2D1 (n=155, 133)	85.5 (18.9)	84.5 (20.6)
Cognitive Functioning: C3D1 (n=154, 106)	87.0 (15.7)	83.8 (20.4)
Cognitive Functioning: C4D1 (n=135, 90)	88.1 (15.6)	82.6 (20.4)
Cognitive Functioning: C5D1 (n=123, 74)	88.9 (14.4)	82.7 (22.0)
Cognitive Functioning: C6D1 (n=120, 70)	87.5 (15.3)	83.8 (19.2)
Cognitive Functioning: C7D1 (n=115, 52)	86.7 (15.6)	85.3 (18.3)
Cognitive Functioning: C8D1 (n=111, 43)	87.8 (14.7)	82.2 (23.4)
Cognitive Functioning: C9D1 (n=101, 37)	88.3 (16.6)	84.7 (21.7)
Cognitive Functioning: C10D1 (n=94, 33)	89.2 (16.0)	80.8 (22.1)
Cognitive Functioning: C11D1 (n=84, 25)	87.9 (14.9)	85.3 (19.4)
Cognitive Functioning: C12D1 (n=76, 23)	89.5 (14.4)	80.4 (22.8)
Cognitive Functioning: C13D1 (n=74, 21)	88.5 (15.6)	79.4 (27.8)
Cognitive Functioning: C14D1 (n=66, 19)	88.9 (14.7)	81.6 (24.1)
Cognitive Functioning: C15D1 (n=62, 16)	87.6 (15.4)	84.4 (18.7)
Cognitive Functioning: C16D1 (n=53, 12)	87.4 (14.2)	72.2 (25.9)
Cognitive Functioning: C17D1 (n=47, 11)	85.1 (15.2)	75.8 (21.6)
Cognitive Functioning: C18D1 (n=44, 11)	88.3 (14.6)	75.8 (25.1)
Cognitive Functioning: C19D1 (n=40, 9)	87.5 (14.5)	70.4 (23.2)
Cognitive Functioning: C20D1 (n=35, 8)	85.7 (15.2)	72.9 (23.5)
Cognitive Functioning: C21D1 (n=30, 8)	85.6 (15.0)	72.9 (23.5)
Cognitive Functioning: C22D1 (n=24, 7)	86.1 (15.3)	69.0 (24.4)
Cognitive Functioning: C23D1 (n=23, 4)	85.5 (14.5)	58.3 (21.5)
Cognitive Functioning: C24D1 (n=20, 3)	85.8 (19.7)	61.1 (34.7)
Cognitive Functioning: C25D1 (n=18, 3)	86.1 (15.4)	55.6 (25.5)
Cognitive Functioning: C26D1 (n=14, 3)	81.0 (26.0)	61.1 (34.7)
Cognitive Functioning: C27D1 (n=14, 2)	76.2 (25.9)	41.7 (11.8)
Cognitive Functioning: C28D1 (n=11, 2)	78.8 (21.2)	41.7 (11.8)
Cognitive Functioning: C29D1 (n=8, 2)	87.5 (11.8)	33.3 (0.0)
Cognitive Functioning: C30D1 (n=8, 1)	83.3 (23.6)	16.7 [1] (NA)
Cognitive Functioning: C31D1 (n=7, 0)	81.0 (20.2)	NA [2] (NA)
Cognitive Functioning: C32D1 (n=6, 0)	83.3 (18.3)	NA [2] (NA)
Cognitive Functioning: C33D1 (n=6, 0)	86.1 (16.4)	NA [2] (NA)
Cognitive Functioning: C34D1 (n=5, 0)	90.0 (9.1)	NA [2] (NA)
Cognitive Functioning: C35D1 (n=4, 0)	95.8 (8.3)	NA [2] (NA)
Cognitive Functioning: C36D1 (n=1, 0)	100.0 [1] (NA)	NA [2] (NA)
Cognitive Functioning: C37D1 (n=1, 0)	83.3 [1] (NA)	NA [2] (NA)
Social Functioning: Baseline (n=165, 162)	68.0 (27.7)	67.1 (29.0)
Social Functioning: C2D1 (n=155, 133)	75.9 (25.1)	69.5 (28.1)
Social Functioning: C3D1 (n=154, 106)	78.5 (24.0)	72.5 (26.7)
Social Functioning: C4D1 (n=135, 90)	79.4 (23.9)	71.7 (26.3)
Social Functioning: C5D1 (n=123, 74)	79.4 (23.8)	74.5 (27.1)
Social Functioning: C6D1 (n=120, 70)	81.8 (22.1)	76.4 (27.3)
Social Functioning: C7D1 (n=115, 52)	82.3 (21.8)	77.9 (24.6)
Social Functioning: C8D1 (n=111, 43)	82.0 (21.3)	77.5 (24.4)
Social Functioning: C9D1 (n=101, 37)	80.4 (24.7)	80.2 (21.8)
Social Functioning: C10D1 (n=94, 33)	81.9 (25.1)	76.3 (27.0)
Social Functioning: C11D1 (n=84, 25)	81.9 (23.0)	78.7 (24.8)
Social Functioning: C12D1 (n=76, 23)	82.0 (23.5)	71.0 (31.9)
Social Functioning: C13D1 (n=74, 21)	81.8 (24.7)	71.4 (28.9)
Social Functioning: C14D1 (n=66, 19)	81.3 (23.8)	69.3 (34.8)
Social Functioning: C15D1 (n=62, 16)	81.5 (25.6)	74.0 (28.5)
Social Functioning: C16D1 (n=53, 12)	82.7 (21.9)	65.3 (35.9)
Social Functioning: C17D1 (n=47, 11)	81.9 (24.8)	69.7 (33.2)
Social Functioning: C18D1 (n=44, 11)	82.6 (22.7)	65.2 (35.3)
Social Functioning: C19D1 (n=40, 9)	84.6 (22.8)	64.8 (31.7)
Social Functioning: C20D1 (n=35, 8)	82.9 (23.7)	70.8 (33.0)
Social Functioning: C21D1 (n=30, 8)	82.8 (24.2)	64.6 (36.1)
Social Functioning: C22D1 (n=24, 7)	82.6 (23.8)	65.5 (39.8)
Social Functioning: C23D1 (n=23, 4)	84.4 (23.9)	41.7 (50.0)
Social Functioning: C24D1 (n=20, 3)	84.2 (27.3)	61.1 (53.6)
Social Functioning: C25D1 (n=18, 3)	89.8 (19.1)	50.0 (50.0)
Social Functioning: C26D1 (n=14, 3)	78.6 (28.8)	50.0 (50.0)
Social Functioning: C27D1 (n=14, 2)	85.7 (15.8)	33.3 (47.1)
Social Functioning: C28D1 (n=11, 2)	83.3 (26.9)	33.3 (47.1)
Social Functioning: C29D1 (n=8, 2)	83.3 (25.2)	33.3 (47.1)
Social Functioning: C30D1 (n=8, 1)	85.4 (24.3)	0.0 [1] (NA)
Social Functioning: C31D1 (n=7, 0)	73.8 (38.3)	NA [2] (NA)
Social Functioning: C32D1 (n=6, 0)	83.3 (18.3)	NA [2] (NA)
Social Functioning: C33D1 (n=6, 0)	94.4 (13.6)	NA [2] (NA)
Social Functioning: C34D1 (n=5, 0)	96.7 (7.5)	NA [2] (NA)
Social Functioning: C35D1 (n=4, 0)	91.7 (16.7)	NA [2] (NA)
Social Functioning: C36D1 (n=1, 0)	66.7 [1] (NA)	NA [2] (NA)
Social Functioning: C37D1 (n=1, 0)	66.7 [1] (NA)	NA [2] (NA)
Fatigue: Baseline (n=165, 163)	38.3 (24.4)	36.1 (25.3)
Fatigue: C2D1 (n=155, 133)	31.4 (23.4)	39.5 (24.8)
Fatigue: C3D1 (n=154, 106)	30.8 (24.1)	39.4 (24.5)
Fatigue: C4D1 (n=135, 91)	27.1 (22.3)	34.1 (22.1)
Fatigue: C5D1 (n=123, 74)	24.7 (19.8)	31.5 (25.2)
Fatigue: C6D1 (n=120, 70)	24.6 (19.3)	31.0 (22.8)
Fatigue: C7D1 (n=115, 52)	23.9 (19.8)	27.6 (23.1)
Fatigue: C8D1 (n=111, 43)	23.2 (18.9)	26.6 (23.6)
Fatigue: C9D1 (n=101, 37)	22.9 (21.7)	28.5 (26.6)
Fatigue: C10D1 (n=94, 33)	21.4 (20.0)	28.6 (27.9)
Fatigue: C11D1 (n=84, 25)	22.1 (19.6)	22.2 (22.9)
Fatigue: C12D1 (n=76, 23)	21.9 (22.9)	26.1 (24.1)
Fatigue: C13D1 (n=74, 21)	23.3 (21.3)	27.5 (25.2)
Fatigue: C14D1 (n=66, 19)	21.7 (21.7)	28.1 (26.8)
Fatigue: C15D1 (n=62, 16)	20.8 (22.5)	24.3 (24.8)
Fatigue: C16D1 (n=53, 12)	22.2 (18.0)	24.1 (21.6)
Fatigue: C17D1 (n=47, 11)	23.4 (20.0)	23.2 (23.0)
Fatigue: C18D1 (n=45, 11)	21.5 (18.3)	27.3 (22.4)
Fatigue: C19D1 (n=40, 9)	20.8 (18.7)	24.7 (20.6)
Fatigue: C20D1 (n=35, 8)	24.4 (19.2)	27.8 (26.6)
Fatigue: C21D1 (n=30, 8)	23.9 (17.8)	25.7 (27.7)
Fatigue: C22D1 (n=24, 7)	23.6 (16.2)	27.0 (23.9)
Fatigue: C23D1 (n=23, 4)	25.1 (19.3)	47.2 (14.0)
Fatigue: C24D1 (n=20, 3)	24.4 (18.9)	40.7 (23.1)
Fatigue: C25D1 (n=18, 3)	24.7 (16.0)	44.4 (19.2)
Fatigue: C26D1 (n=14, 3)	30.2 (25.6)	44.4 (19.2)
Fatigue: C27D1 (n=14, 2)	35.7 (25.1)	55.6 (15.7)
Fatigue: C28D1 (n=11, 2)	28.3 (22.4)	38.9 (7.9)
Fatigue: C29D1 (n=8, 2)	30.6 (22.8)	50.0 (23.6)
Fatigue: C30D1 (n=8, 1)	26.4 (24.4)	55.6 [1] (NA)
Fatigue: C31D1 (n=7, 0)	28.6 (16.8)	NA [2] (NA)
Fatigue: C32D1 (n=6, 0)	25.9 (5.7)	NA [1] (NA)
Fatigue: C33D1 (n=6, 0)	18.5 (11.5)	NA [2] (NA)
Fatigue: C34D1 (n=5, 0)	15.6 (16.9)	NA [2] (NA)
Fatigue: C35D1 (n=4, 0)	27.8 (14.3)	NA [2] (NA)
Fatigue: C36D1 (n=1, 0)	33.3 [1] (NA)	NA [2] (NA)
Fatigue: C37D1 (n=1, 0)	11.1 [1] (NA)	NA [2] (NA)
Nausea and Vomiting: Baseline (n=165, 163)	8.4 (14.4)	11.7 (18.0)
Nausea and Vomiting: C2D1 (n=155, 133)	15.2 (20.9)	12.7 (19.0)
Nausea and Vomiting: C3D1 (n=154, 106)	13.9 (21.2)	9.9 (16.6)
Nausea and Vomiting: C4D1 (n=135, 91)	9.9 (18.1)	8.1 (14.1)
Nausea and Vomiting: C5D1 (n=123, 74)	9.2 (14.7)	9.0 (16.8)
Nausea and Vomiting: C6D1 (n=120, 70)	10.1 (15.2)	6.9 (13.2)
Nausea and Vomiting: C7D1 (n=115, 52)	7.1 (11.9)	7.7 (11.7)
Nausea and Vomiting: C8D1 (n=111, 43)	8.8 (13.7)	8.9 (14.7)
Nausea and Vomiting: C9D1 (n=101, 37)	6.9 (13.0)	9.5 (19.9)
Nausea and Vomiting: C10D1 (n=94, 33)	8.5 (14.6)	8.1 (15.7)
Nausea and Vomiting: C11D1 (n=84, 25)	8.3 (12.8)	8.0 (16.0)
Nausea and Vomiting: C12D1 (n=76, 23)	6.4 (12.8)	7.2 (15.8)
Nausea and Vomiting: C13D1 (n=74, 21)	8.6 (14.1)	7.1 (16.3)
Nausea and Vomiting: C14D1 (n=66, 19)	5.8 (13.9)	7.0 (14.0)
Nausea and Vomiting: C15D1 (n=62, 16)	5.9 (11.3)	6.2 (13.4)
Nausea and Vomiting: C16D1 (n=53, 12)	5.3 (9.7)	6.9 (11.1)
Nausea and Vomiting: C17D1 (n=47, 11)	7.8 (12.5)	10.6 (11.2)
Nausea and Vomiting: C18D1 (n=45, 11)	7.0 (13.5)	3.0 (6.7)
Nausea and Vomiting: C19D1 (n=40, 9)	8.8 (14.6)	9.3 (12.1)
Nausea and Vomiting: C20D1 (n=35, 8)	7.4 (13.5)	10.4 (15.3)
Nausea and Vomiting: C21D1 (n=30, 8)	7.8 (12.9)	8.3 (12.6)
Nausea and Vomiting: C22D1 (n=24, 7)	2.8 (6.3)	14.3 (17.8)
Nausea and Vomiting: C23D1 (n=23, 4)	5.4 (10.5)	45.8 (21.0)
Nausea and Vomiting: C24D1 (n=20, 3)	7.5 (14.8)	33.3 (28.9)
Nausea and Vomiting: C25D1 (n=18, 3)	3.7 (9.1)	27.8 (25.5)
Nausea and Vomiting: C26D1 (n=14, 3)	10.7 (27.4)	33.3 (16.7)
Nausea and Vomiting: C27D1 (n=14, 2)	11.9 (27.3)	33.3 (23.6)
Nausea and Vomiting: C28D1 (n=11, 2)	3.0 (6.7)	25.0 (11.8)
Nausea and Vomiting: C29D1 (n=8, 2)	10.4 (15.3)	25.0 (11.8)
Nausea and Vomiting: C30D1 (n=8, 1)	6.3 (12.4)	33.3 [1] (NA)
Nausea and Vomiting: C31D1 (n=7, 0)	14.3 (17.8)	NA [2] (NA)
Nausea and Vomiting: C32D1 (n=6, 0)	11.1 (17.2)	NA [2] (NA)
Nausea and Vomiting: C33D1 (n=6, 0)	11.1 (17.2)	NA [2] (NA)
Nausea and Vomiting: C34D1 (n=5, 0)	13.3 (18.3)	NA [2] (NA)
Nausea and Vomiting: C35D1 (n=4, 0)	12.5 (16.0)	NA [2] (NA)
Nausea and Vomiting: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Nausea and Vomiting: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Pain: Baseline (n=165, 163)	23.9 (24.7)	28.0 (27.3)
Pain: C2D1 (n=155, 133)	13.9 (19.8)	25.7 (25.3)
Pain: C3D1 (n=154, 106)	13.7 (20.4)	23.3 (26.6)
Pain: C4D1 (n=135, 91)	13.0 (19.5)	19.0 (21.5)
Pain: C5D1 (n=123, 74)	11.5 (16.7)	20.5 (23.0)
Pain: C6D1 (n=120, 70)	10.6 (15.0)	19.5 (23.0)
Pain: C7D1 (n=115, 52)	9.6 (14.3)	21.5 (24.3)
Pain: C8D1 (n=111, 43)	11.3 (18.0)	17.4 (23.6)
Pain: C9D1 (n=101, 37)	11.8 (18.8)	23.0 (27.6)
Pain: C10D1 (n=94, 33)	8.7 (14.0)	24.2 (28.6)
Pain: C11D1 (n=84, 25)	10.5 (16.3)	22.0 (27.9)
Pain: C12D1 (n=76, 23)	8.6 (14.3)	25.4 (29.7)
Pain: C13D1 (n=74, 21)	10.1 (15.3)	27.8 (30.4)
Pain: C14D1 (n=66, 19)	8.1 (12.8)	23.7 (26.2)
Pain: C15D1 (n=62, 16)	9.4 (15.6)	22.9 (25.7)
Pain: C16D1 (n=53, 12)	9.4 (14.4)	31.9 (28.8)
Pain: C17D1 (n=47, 11)	10.6 (16.1)	24.2 (27.2)
Pain: C18D1 (n=45, 11)	11.1 (18.1)	24.2 (29.2)
Pain: C19D1 (n=40, 9)	11.3 (17.0)	24.1 (20.6)
Pain: C20D1 (n=35, 8)	11.9 (18.8)	22.9 (28.1)
Pain: C21D1 (n=30, 8)	11.7 (15.3)	29.2 (30.5)
Pain: C22D1 (n=24, 7)	6.9 (12.9)	33.3 (28.9)
Pain: C23D1 (n=23, 4)	9.1 (16.1)	33.3 (36.0)
Pain: C24D1 (n=20, 3)	4.2 (11.9)	27.8 (48.1)
Pain: C25D1 (n=18, 3)	4.6 (7.7)	38.9 (41.9)
Pain: C26D1 (n=14, 3)	17.9 (27.3)	38.9 (41.9)
Pain: C27D1 (n=14, 2)	13.1 (25.5)	58.3 (35.4)
Pain: C28D1 (n=11, 2)	4.5 (7.8)	50.0 (47.1)
Pain: C29D1 (n=8, 2)	2.1 (5.9)	41.7 (35.4)
Pain: C30D1 (n=8, 1)	4.2 (7.7)	83.3 [1] (NA)
Pain: C31D1 (n=7, 0)	4.8 (8.1)	NA [2] (NA)
Pain: C32D1 (n=6, 0)	5.6 (8.6)	NA [2] (NA)
Pain: C33D1 (n=6, 0)	2.8 (6.8)	NA [2] (NA)
Pain: C34D1 (n=5, 0)	3.3 (7.5)	NA [2] (NA)
Pain: C35D1 (n=4, 0)	8.3 (16.7)	NA [2] (NA)
Pain: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Pain: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Dyspnea: Baseline (n=165, 163)	31.1 (28.3)	32.5 (28.2)
Dyspnea: C2D1 (n=155, 133)	21.5 (21.4)	33.6 (27.7)
Dyspnea: C3D1 (n=154, 106)	21.6 (23.0)	33.3 (28.4)
Dyspnea: C4D1 (n=135, 91)	17.3 (20.7)	29.3 (26.2)
Dyspnea: C5D1 (n=123, 74)	16.0 (20.6)	29.3 (24.0)
Dyspnea: C6D1 (n=120, 70)	15.8 (22.0)	26.2 (24.7)
Dyspnea: C7D1 (n=115, 52)	17.4 (20.9)	28.2 (22.3)
Dyspnea: C8D1 (n=111, 43)	15.8 (19.7)	22.5 (28.8)
Dyspnea: C9D1 (n=101, 37)	13.9 (19.0)	23.4 (24.7)
Dyspnea: C10D1 (n=94, 33)	17.7 (20.6)	24.2 (22.5)
Dyspnea: C11D1 (n=84, 25)	17.5 (22.8)	25.3 (22.1)
Dyspnea: C12D1 (n=76, 23)	14.5 (19.9)	30.4 (28.3)
Dyspnea: C13D1 (n=74, 21)	14.0 (20.6)	23.8 (23.9)
Dyspnea: C14D1 (n=66, 19)	15.2 (21.2)	29.8 (24.6)
Dyspnea: C15D1 (n=62, 16)	15.6 (21.5)	20.8 (20.6)
Dyspnea: C16D1 (n=53, 12)	13.8 (17.8)	19.4 (22.3)
Dyspnea: C17D1 (n=46, 11)	14.5 (20.7)	24.2 (21.6)
Dyspnea: C18D1 (n=45, 11)	14.1 (16.6)	24.2 (26.2)
Dyspnea: C19D1 (n=40, 9)	14.2 (18.3)	25.9 (22.2)
Dyspnea: C20D1 (n=35, 8)	10.5 (17.7)	33.3 (25.2)
Dyspnea: C21D1 (n=30, 8)	13.3 (16.6)	33.3 (17.8)
Dyspnea: C22D1 (n=24, 7)	13.9 (19.5)	28.6 (23.0)
Dyspnea: C23D1 (n=23, 4)	9.4 (14.9)	41.7 (16.7)
Dyspnea: C24D1 (n=20, 3)	18.3 (20.2)	44.4 (19.2)
Dyspnea: C25D1 (n=18, 3)	11.1 (16.2)	33.3 (33.3)
Dyspnea: C26D1 (n=14, 3)	14.3 (28.4)	33.3 (33.3)
Dyspnea: C27D1 (n=14, 2)	11.9 (16.6)	50.0 (23.6)
Dyspnea: C28D1 (n=11, 2)	12.1 (16.8)	50.0 (23.6)
Dyspnea: C29D1 (n=8, 2)	4.2 (11.8)	50.0 (23.6)
Dyspnea: C30D1 (n=8, 1)	8.3 (15.4)	66.7 [1] (NA)
Dyspnea: C31D1 (n=7, 0)	9.5 (16.3)	NA [2] (NA)
Dyspnea: C32D1 (n=6, 0)	16.7 (18.3)	NA [2] (NA)
Dyspnea: C33D1 (n=6, 0)	11.1 (17.2)	NA [2] (NA)
Dyspnea: C34D1 (n=5, 0)	13.3 (18.3)	NA [2] (NA)
Dyspnea: C35D1 (n=4, 0)	16.7 (19.2)	NA [2] (NA)
Dyspnea: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Dyspnea: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Insomnia : Baseline (n=164, 163)	22.6 (26.4)	27.8 (27.3)
Insomnia : C2D1 (n=155, 133)	15.3 (23.5)	27.1 (25.3)
Insomnia : C3D1 (n=154, 106)	16.2 (26.2)	23.6 (26.0)
Insomnia : C4D1 (n=135, 91)	13.3 (21.2)	23.8 (26.9)
Insomnia : C5D1 (n=123, 74)	13.6 (21.3)	25.7 (26.8)
Insomnia : C6D1 (n=120, 70)	14.2 (21.9)	23.3 (25.0)
Insomnia : C7D1 (n=114, 52)	9.4 (17.5)	21.8 (25.5)
Insomnia : C8D1 (n=111, 43)	12.5 (21.5)	21.7 (22.9)
Insomnia : C9D1 (n=100, 37)	12.3 (21.5)	22.5 (24.9)
Insomnia : C10D1 (n=94, 33)	13.5 (23.6)	24.2 (25.4)
Insomnia : C11D1 (n=84, 25)	13.9 (22.1)	22.7 (24.9)
Insomnia : C12D1 (n=76, 23)	13.6 (21.9)	23.2 (25.5)
Insomnia : C13D1 (n=74, 21)	10.8 (19.2)	25.4 (25.6)
Insomnia : C14D1 (n=66, 19)	11.1 (18.8)	24.6 (29.1)
Insomnia : C15D1 (n=62, 16)	11.3 (20.0)	29.2 (26.9)
Insomnia : C16D1 (n=53, 11)	13.8 (20.1)	21.2 (22.5)
Insomnia : C17D1 (n=47, 11)	13.5 (21.6)	15.2 (22.9)
Insomnia : C18D1 (n=45, 11)	12.6 (17.8)	21.2 (27.0)
Insomnia : C19D1 (n=40, 9)	13.3 (19.7)	22.2 (28.9)
Insomnia : C20D1 (n=35, 8)	15.2 (20.4)	20.8 (24.8)
Insomnia : C21D1 (n=30, 8)	12.2 (18.5)	29.2 (27.8)
Insomnia : C22D1 (n=24, 7)	12.5 (19.2)	31.0 (24.4)
Insomnia : C23D1 (n=23, 4)	17.4 (26.3)	50.0 (19.2)
Insomnia : C24D1 (n=20, 3)	11.7 (22.4)	22.2 (38.5)
Insomnia : C25D1 (n=18, 3)	20.4 (30.5)	44.4 (19.2)
Insomnia : C26D1 (n=14, 3)	21.4 (33.6)	22.2 (38.5)
Insomnia : C27D1 (n=14, 2)	16.7 (21.7)	50.0 (23.6)
Insomnia : C28D1 (n=11, 2)	9.1 (15.6)	50.0 (23.6)
Insomnia : C29D1 (n=8, 2)	8.3 (15.4)	33.0 (0.0)
Insomnia : C30D1 (n=8, 1)	12.5 (24.8)	33.3 [1] (NA)
Insomnia : C31D1 (n=7, 0)	0.0 (0.0)	NA [2] (NA)
Insomnia : C32D1 (n=6, 0)	5.6 (13.6)	NA [2] (NA)
Insomnia : C33D1 (n=6, 0)	5.6 (13.6)	NA [2] (NA)
Insomnia : C34D1 (n=5, 0)	13.3 (18.3)	NA [2] (NA)
Insomnia : C35D1 (n=4, 0)	16.7 (19.2)	NA [2] (NA)
Insomnia : C36D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Insomnia : C37D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Appetite loss : Baseline(n=165, 163)	24.4 (28.8)	23.3 (28.2)
Appetite loss : C2/D1(n=155, 133)	21.1 (30.2)	24.3 (28.5)
Appetite loss : C3/D1(n=154, 106)	18.4 (29.0)	21.7 (27.2)
Appetite loss : C4/D1(n=135, 91)	14.6 (24.3)	19.4 (23.3)
Appetite loss : C5/D1(n=123, 74)	12.7 (22.4)	19.4 (28.1)
Appetite loss : C6/D1(n=120, 70)	13.6 (21.8)	12.9 (23.6)
Appetite loss : C7/D1(n=115, 52)	10.4 (19.4)	12.8 (22.0)
Appetite loss : C8/D1(n=111, 43)	12.8 (20.8)	10.9 (22.7)
Appetite loss : C9/D1(n=101, 37)	12.2 (239)	14.4 (27.8)
Appetite loss : C10/D1(n=94, 33)	12.4 (22.9)	14.1 (25.0)
Appetite loss : C11/D1(n=84, 25)	13.5 (19.4)	14.7 (25.6)
Appetite loss : C12/D1(n=76, 23)	11.0 (21.4)	14.5 (24.3)
Appetite loss : C13/D1(n=74, 21)	9.5 (20.3)	17.5 (27.1)
Appetite loss : C15/D1(n=62, 16)	8.6 (20.9)	12.5 (26.9)
Appetite loss : C16/D1(n=53, 12)	8.8 (18.7)	16.7 (30.2)
Appetite loss : C17/D1(n=47, 11)	8.5 (16.3)	15.2 (31.1)
Appetite loss : C18/D1(n=45, 11)	11.1 (17.4)	12.1 (22.5)
Appetite loss : C19/D1(n=40, 9)	8.3 (16.5)	18.5 (33.8)
Appetite loss : C20/D1(n=35, 8)	7.6 (16.3)	20.8 (35.4)
Appetite loss : C21/D1(n=30, 8)	11.1 (16.0)	25.0 (34.5)
Appetite loss : C22/D1(n=24, 7)	6.9 (13.8)	14.3 (37.8)
Appetite loss : C23/D1(n=23, 4)	9.4 (14.9)	50.0 (43.0)
Appetite loss : C24/D1(n=20, 3)	5.0 (12.2)	33.3 (33.3)
Appetite loss : C25/D1(n=18, 3)	1.9 (7.9)	44.4 (50.9)
Appetite loss : C26/D1(n=14, 3)	11.9 (21.1)	33.3 (33.3)
Appetite loss : C27/D1(n=14, 2)	7.1 (19.3)	33.3 (47.1)
Appetite loss : C28/D1(n=11, 2)	15.2 (17.4)	33.3 (47.1)
Appetite loss : C29/D1(n=8, 2)	12.5 (17.3)	33.3 (47.1)
Appetite loss : C30/D1(n=8, 1)	8.3 (15.4)	100.0 [1] (NA)
Appetite loss : C31/D1(n=7, 0)	14.3 (17.8)	NA [2] (NA)
Constipation: Baseline (n=164, 162)	14.8 (25.1)	16.9 (25.0)
Constipation: C2D1 (n=155, 133)	28.6 (30.5)	14.0 (24.3)
Constipation: C3D1 (n=154, 106)	27.1 (30.0)	16.0 (22.2)
Constipation: C4D1 (n=134, 90)	22.9 (26.6)	14.8 (25.5)
Constipation: C5D1 (n=123, 74)	21.4 (25.7)	20.3 (29.6)
Constipation: C6D1 (n=120, 70)	21.7 (23.9)	15.7 (23.2)
Constipation: C7D1 (n=115, 52)	21.7 (26.1)	19.9 (26.6)
Constipation: C8D1 (n=111, 43)	18.6 (24.1)	16.3 (24.5)
Constipation: C9D1 (n=101, 37)	18.8 (22.3)	16.2 (21.7)
Constipation: C10D1 (n=94, 33)	16.0 (22.8)	19.2 (25.0)
Constipation: C11D1 (n=84, 25)	21.0 (25.8)	21.3 (19.0)
Constipation: C12D1 (n=76, 23)	19.7 (24.5)	21.7 (23.8)
Constipation: C13D1 (n=74, 21)	21.2 (26.2)	22.2 (26.5)
Constipation: C14D1 (n=66, 19)	21.7 (27.1)	24.6 (31.1)
Constipation: C15D1 (n=62, 16)	22.6 (27.5)	18.7 (21.0)
Constipation: C16D1 (n=53, 12)	19.5 (26.5)	22.2 (25.9)
Constipation: C17D1 (n=47, 11)	22.0 (27.2)	24.2 (30.2)
Constipation: C18D1 (n=44, 11)	22.7 (25.7)	15.2 (22.9)
Constipation: C19D1 (n=40, 9)	25.0 (25.9)	22.2 (23.6)
Constipation: C20D1 (n=35, 8)	22.9 (26.5)	20.8 (24.8)
Constipation: C21D1 (n=30, 8)	24.4 (28.9)	16.7 (25.2)
Constipation: C22D1 (n=24, 7)	18.1 (24.0)	19.0 (26.2)
Constipation: C23D1 (n=23, 4)	11.6 (19.1)	25.0 (31.9)
Constipation: C24D1 (n=20, 3)	21.7 (24.8)	22.2 (19.2)
Constipation: C25D1 (n=18, 3)	22.2 (32.3)	33.3 (33.3)
Constipation: C26D1 (n=14, 3)	26.2 (32.5)	44.4 (50.9)
Constipation: C27D1 (n=14, 2)	35.7 (40.2)	50.0 (23.6)
Constipation: C28D1 (n=11, 2)	21.2 (16.8)	50.0 (23.6)
Constipation: C29D1 (n=8, 2)	29.2 (21.4)	50.0 (23.6)
Constipation: C30D1 (n=8, 1)	29.2 (27.8)	33.3 [1] (NA)
Constipation: C31D1 (n=7, 0)	33.3 (27.2)	NA [2] (NA)
Constipation: C32D1 (n=6, 0)	33.3 (42.2)	NA [2] (NA)
Constipation: C33D1 (n=6, 0)	38.9 (25.1)	NA [2] (NA)
Constipation: C34D1 (n=5, 0)	40.0 (43.5)	NA [2] (NA)
Constipation: C35D1 (n=4, 0)	33.3 (27.2)	NA [2] (NA)
Constipation: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Constipation: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Constipation: EOT (n=49, 90)	28.6 (27.2)	18.1 (25.6)
Diarrhea: Baseline (n=165, 162)	9.7 (19.1)	7.8 (16.0)
Diarrhea: C2D1 (n=155, 132)	18.1 (26.7)	11.1 (20.5)
Diarrhea: C3D1 (n=153, 106)	21.6 (28.7)	7.9 (18.1)
Diarrhea: C4D1 (n=134, 90)	23.1 (26.9)	8.5 (18.4)
Diarrhea: C5D1 (n=123, 74)	24.4 (25.6)	5.9 (15.0)
Diarrhea: C6D1 (n=120, 70)	22.2 (26.4)	7.1 (16.9)
Diarrhea: C7D1 (n=115, 52)	20.6 (24.8)	9.6 (16.6)
Diarrhea: C8D1 (n=111, 43)	18.6 (24.1)	9.3 (19.7)
Diarrhea: C9D1 (n=101, 37)	17.3 (22.8)	7.2 (16.0)
Diarrhea: C10D1 (n=94, 33)	17.7 (22.3)	7.1 (16.2)
Diarrhea: C11D1 (n=84, 25)	21.0 (22.4)	8.0 (17.4)
Diarrhea: C12D1 (n=76, 23)	17.5 (25.2)	8.7 (15.0)
Diarrhea: C13D1 (n=74, 21)	17.6 (23.6)	12.7 (19.7)
Diarrhea: C14D1 (n=66, 19)	17.7 (22.8)	8.8 (18.7)
Diarrhea: C15D1 (n=62, 16)	16.1 (21.5)	4.2 (11.4)
Diarrhea: C16D1 (n=52, 12)	16.0 (20.3)	5.6 (13.0)
Diarrhea: C17D1 (n=47, 11)	19.9 (22.7)	12.1 (22.5)
Diarrhea: C18D1 (n=44, 11)	22.7 (25.7)	12.1 (22.5)
Diarrhea: C19D1 (n=40, 9)	21.7 (25.7)	7.4 (14.7)
Diarrhea: C20D1 (n=35, 8)	21.0 (24.4)	4.2 (11.8)
Diarrhea: C21D1 (n=30, 8)	22.2 (22.0)	8.3 (15.4)
Diarrhea: C22D1 (n=24, 7)	23.6 (25.0)	11.9 (15.9)
Diarrhea: C23D1 (n=23, 4)	15.9 (19.8)	25.0 (16.7)
Diarrhea: C24D1 (n=20, 3)	21.7 (22.4)	11.1 (19.2)
Diarrhea: C25D1 (n=18, 3)	20.4 (25.9)	22.2 (19.2)
Diarrhea: C26D1 (n=14, 3)	19.0 (25.2)	11.1 (19.2)
Diarrhea: C27D1 (n=14, 2)	23.8 (30.5)	16.7 (23.6)
Diarrhea: C28D1 (n=11, 2)	15.2 (17.4)	16.7 (23.6)
Diarrhea: C29D1 (n=8, 2)	20.8 (24.8)	16.7 (23.6)
Diarrhea: C30D1 (n=8, 1)	12.5 (17.3)	0.0 [1] (NA)
Diarrhea: C31D1 (n=7, 0)	14.3 (17.8)	NA [2] (NA)
Diarrhea: C32D1 (n=6, 0)	11.1 (17.2)	NA [2] (NA)
Diarrhea: C33D1 (n=6, 0)	11.1 (17.2)	NA [2] (NA)
Diarrhea: C34D1 (n=5, 0)	6.7 (14.9)	NA [2] (NA)
Diarrhea: C35D1 (n=4, 0)	16.7 (19.2)	NA [2] (NA)
Diarrhea: C36D1 (n=1, 0)	33.3 [1] (NA)	NA [2] (NA)
Diarrhea: C37D1 (n=1, 0)	33.3 [1] (NA)	NA [2] (NA)
Diarrhea: EOT (n=49, 90)	18.4 (23.6)	10.0 (21.5)
Financial Difficulties: Baseline (n=165, 161)	28.5 (33.0)	27.3 (30.7)
Financial Difficulties: C2D1 (n=155, 133)	21.9 (27.2)	22.3 (28.9)
Financial Difficulties: C3D1 (n=154, 105)	19.0 (26.6)	20.3 (27.9)
Financial Difficulties: C4D1 (n=135, 90)	17.5 (26.0)	21.9 (26.0)
Financial Difficulties: C5D1 (n=123, 74)	16.8 (25.0)	19.4 (23.4)
Financial Difficulties: C6D1 (n=120, 70)	15.6 (24.0)	18.6 (25.1)
Financial Difficulties: C7D1 (n=115, 52)	14.8 (21.3)	18.6 (25.9)
Financial Difficulties: C8D1 (n=111, 43)	16.8 (25.0)	15.5 (23.4)
Financial Difficulties: C9D1 (n=101, 36)	17.8 (26.1)	16.7 (23.2)
Financial Difficulties: C10D1 (n=94, 33)	16.3 (26.2)	15.2 (23.7)
Financial Difficulties: C11D1 (n=84, 25)	17.5 (25.1)	17.3 (21.8)
Financial Difficulties: C12D1 (n=76, 23)	17.1 (24.6)	18.8 (28.1)
Financial Difficulties: C13D1 (n=74, 21)	16.2 (24.2)	17.5 (27.1)
Financial Difficulties: C14D1 (n=66, 19)	14.1 (20.3)	17.5 (32.1)
Financial Difficulties: C15D1 (n=62, 16)	14.0 (23.0)	16.7 (27.2)
Financial Difficulties: C16D1 (n=53, 12)	15.7 (25.0)	30.6 (36.1)
Financial Difficulties: C17D1 (n=47, 11)	17.7 (29.4)	33.3 (36.5)
Financial Difficulties: C18D1 (n=44, 11)	18.9 (30.0)	15.2 (31.1)
Financial Difficulties: C19D1 (n=40, 9)	17.5 (31.1)	25.9 (32.4)
Financial Difficulties: C20D1 (n=35, 8)	16.2 (27.3)	25.0 (34.5)
Financial Difficulties: C21D1 (n=30, 8)	13.3 (27.1)	29.2 (33.0)
Financial Difficulties: C22D1 (n=24, 7)	18.1 (31.1)	28.6 (35.6)
Financial Difficulties: C23D1 (n=23, 4)	17.4 (31.6)	33.3 (47.1)
Financial Difficulties: C24D1 (n=20, 3)	20.0 (33.2)	33.3 (57.7)
Financial Difficulties: C25D1 (n=18, 3)	11.1 (16.2)	44.4 (50.9)
Financial Difficulties: C26D1 (n=14, 3)	14.3 (17.1)	44.4 (50.9)
Financial Difficulties: C27D1 (n=14, 2)	14.3 (17.1)	66.7 (47.1)
Financial Difficulties: C28D1 (n=11, 2)	15.2 (22.9)	66.7 (47.1)
Financial Difficulties: C29D1 (n=8, 2)	8.3 (15.4)	66.7 (47.1)
Financial Difficulties: C30D1 (n=8, 1)	4.2 (11.8)	100.0 [1] (NA)
Financial Difficulties: C31D1 (n=7, 0)	9.5 (16.3)	NA [2] (NA)
Financial Difficulties: C32D1 (n=6, 0)	22.2 (27.2)	NA [2] (NA)
Financial Difficulties: C33D1 (n=6, 0)	16.7 (27.9)	NA [2] (NA)
Financial Difficulties: C34D1 (n=5, 0)	13.3 (18.3)	NA [2] (NA)
Financial Difficulties: C35D1 (n=4, 0)	8.3 (16.7)	NA [2] (NA)
Financial Difficulties: C36D1 (n=1, 0)	33.3 [1] (NA)	NA [2] (NA)
Financial Difficulties: C37D1 (n=1, 0)	66.7 [1] (NA)	NA [2] (NA)
Financial Difficulties: EOT (n=49, 90)	17.0 (27.3)	24.1 (30.0)
Appetite loss: C32D1 (n=6, 0)	11.1 (17.2)	NA [2] (NA)
Appetite loss: C33D1 (n=6, 0)	11.1 (17.2)	NA [2] (NA)
Appetite loss: C34D1 (n=5, 0)	13.3 (18.3)	NA [2] (NA)
Appetite loss: C35D1 (n=4, 0)	16.7 (19.2)	NA [2] (NA)
Appetite loss: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Appetite loss: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [2] (NA)
Appetite loss: EOT (n=49, 90)	21.8 (26.0)	28.1 (30.4)
Global Qol: EOT (n=49, 90)	56.1 (24.5)	46.4 (25.4)
Physical Functioning: EOT (n=49, 90)	80.7 (23.0)	66.2 (27.7)
Role Functioning: EOT (n=49, 90)	71.8 (27.7)	54.1 (34.7)
Emotional Functioning: EOT (n=49, 90)	75.2 (25.1)	74.5 (25.2)
Cognitive Functioning: EOT (n=49, 90)	83.7 (20.3)	80.0 (24.0)
Social Function: EOT (n=49, 90)	78.2 (27.9)	59.4 (33.5)
Fatigue: EOT (n=49, 90)	32.0 (28.2)	46.9 (26.9)
Nausea and Vomiting: EOT (n=49, 90)	16.3 (22.9)	15.7 (20.4)
Pain: EOT (n=49, 90)	23.8 (30.4)	33.7 (31.3)
Dyspnea: EOT (n=49, 90)	23.8 (28.1)	40.0 (30.1)
Insomnia: EOT (n=49, 90)	18.4 (24.6)	30.4 (27.7)

[1]

Standard deviation was not estimable since only one participant was evaluable.

[2]

Data was not analyzed as no participants were evaluable.

14. Secondary Outcome

Title	European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)
Description	QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: 1 'Not at All' to 4 'Very Much'. Scores averaged, transformed to 0-100 scale; higher symptom score = greater degree of symptoms.
Time Frame	Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for specified time points for each arm group, respectively.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	164	162
Mean (Standard Deviation); Unit of Measure: units on a scale
Dyspnea: Baseline (n=164, 162)	27.2 (21.7)	26.9 (23.4)
Dyspnea: C2D1 (n=155, 132)	17.6 (18.1)	28.6 (22.3)
Dyspnea: C3D1 (n=153, 106)	17.9 (17.8)	28.0 (25.4)
Dyspnea: C4D1 (n=135, 91)	16.2 (17.5)	27.5 (22.8)
Dyspnea: C5D1 (n=123, 74)	16.9 (16.7)	24.8 (22.9)
Dyspnea: C6D1 (n=119, 70)	15.2 (15.8)	25.2 (23.0)
Dyspnea: C7D1 (n=115, 52)	15.6 (16.5)	24.4 (20.3)
Dyspnea: C8D1 (n=111, 43)	14.7 (16.0)	22.0 (22.8)
Dyspnea: C9D1 (n=101, 37)	13.9 (15.8)	19.5 (19.0)
Dyspnea: C10D1 (n=94, 33)	15.4 (17.0)	21.5 (21.0)
Dyspnea: C11D1 (n=84, 25)	15.1 (17.5)	20.4 (24.1)
Dyspnea: C12D1 (n=76, 23)	13.7 (15.5)	22.7 (22.1)
Dyspnea: C13D1 (n=74, 21)	12.8 (14.0)	26.5 (25.9)
Dyspnea: C14D1 (n=66, 19)	14.8 (16.9)	26.3 (26.8)
Dyspnea: C15D1 (n=62, 16)	13.2 (15.4)	22.9 (18.4)
Dyspnea: C16D1 (n=53, 12)	12.6 (11.7)	22.2 (18.3)
Dyspnea: C17D1 (n=46, 11)	12.3 (11.5)	30.3 (23.9)
Dyspnea: C18D1 (n=45, 11)	14.1 (13.5)	26.3 (20.7)
Dyspnea: C19D1 (n=40, 9)	14.4 (13.8)	23.5 (15.2)
Dyspnea: C20D1 (n=35, 8)	13.7 (12.9)	34.7 (24.1)
Dyspnea: C21D1 (n=30, 8)	12.6 (13.0)	25.0 (14.2)
Dyspnea: C22D1 (n=24, 7)	10.6 (11.1)	27.0 (21.1)
Dyspnea: C23D1 (n=23, 4)	13.8 (14.2)	52.8 (19.0)
Dyspnea: C24D1 (n=20, 3)	14.4 (14.9)	48.1 (23.1)
Dyspnea: C25D1 (n=18, 3)	15.4 (12.1)	40.7 (23.1)
Dyspnea: C26D1 (n=14, 3)	14.3 (10.2)	44.4 (22.2)
Dyspnea: C27D1 (n=14, 2)	15.1 (11.2)	55.6 (0.0)
Dyspnea: C28D1 (n=11, 2)	11.1 (8.6)	61.1 (7.9)
Dyspnea: C29D1 (n=8, 2)	12.5 (11.0)	50.0 (7.9)
Dyspnea: C30D1 (n=8, 1)	9.7 (7.1)	77.8 [1] (NA)
Dyspnea: C31D1 (n=7, 0)	15.9 (8.7)	NA [2] (NA)
Dyspnea: C32D1 (n=6, 0)	18.5 (9.1)	NA [2] (NA)
Dyspnea: C33D1 (n=6, 0)	18.5 (9.1)	NA [2] (NA)
Dyspnea: C34D1 (n=5, 0)	20.0 (5.0)	NA [2] (NA)
Dyspnea: C35D1 (n=4, 0)	16.7 (6.4)	NA [2] (NA)
Dyspnea: C36D1 (n=1, 0)	22.2 [1] (NA)	NA [2] (NA)
Dyspnea: C37D1 (n=1, 0)	11.1 [1] (NA)	NA [2] (NA)
Dyspnea: EOT (n=49, 90)	21.8 (19.0)	35.6 (26.7)
Coughing: Baseline (n=164, 162)	38.2 (27.4)	42.2 (31.3)
Coughing: C2D1 (n=155, 132)	23.0 (19.6)	34.8 (26.3)
Coughing: C3D1 (n=153, 106)	23.5 (21.6)	32.4 (27.4)
Coughing: C4D1 (n=135, 91)	19.8 (22.4)	27.1 (24.8)
Coughing: C5D1 (n=123, 74)	18.4 (21.0)	25.7 (25.0)
Coughing: C6D1 (n=119, 70)	14.6 (18.2)	30.0 (25.5)
Coughing: C7D1 (n=115, 52)	15.9 (18.4)	26.3 (23.2)
Coughing: C8D1 (n=111, 43)	13.2 (18.7)	22.5 (23.8)
Coughing: C9D1 (n=101, 37)	13.5 (18.4)	25.2 (28.8)
Coughing: C10D1 (n=94, 33)	14.2 (19.2)	20.2 (26.3)
Coughing: C11D1 (n=83, 25)	12.9 (20.7)	18.7 (25.6)
Coughing: C12D1 (n=76, 23)	14.5 (20.6)	23.2 (25.5)
Coughing: C13D1 (n=74, 21)	14.0 (21.4)	27.0 (27.1)
Coughing: C14D1 (n=66, 19)	13.1 (19.3)	24.6 (31.1)
Coughing: C15D1 (n=62, 16)	11.8 (21.0)	20.8 (20.6)
Coughing: C16D1 (n=53, 12)	13.8 (19.0)	22.2 (21.7)
Coughing: C17D1 (n=47, 11)	6.4 (15.0)	27.3 (25.0)
Coughing: C18D1 (n=45, 11)	13.3 (18.0)	18.2 (17.4)
Coughing: C19D1 (n=40, 9)	12.5 (18.0)	14.8 (17.6)
Coughing: C20D1 (n=35, 8)	10.5 (15.7)	29.2 (21.4)
Coughing: C21D1 (n=30, 8)	13.3 (24.1)	33.3 (25.2)
Coughing: C22D1 (n=24, 7)	8.3 (14.7)	28.6 (23.0)
Coughing: C23D1 (n=23, 4)	11.6 (19.1)	33.3 (0.0)
Coughing: C24D1 (n=20, 3)	8.3 (14.8)	44.4 (19.2)
Coughing: C25D1 (n=18, 3)	5.6 (12.8)	44.4 (19.2)
Coughing: C26D1 (n=14, 3)	2.4 (8.9)	33.3 (0.0)
Coughing: C27D1 (n=14, 2)	7.1 (14.2)	50.0 (23.6)
Coughing: C28D1 (n=11, 2)	18.2 (31.1)	50.0 (23.6)
Coughing: C29D1 (n=8, 2)	8.3 (15.4)	33.3 (0.0)
Coughing: C30D1 (n=8, 1)	20.8 (24.8)	33.3 [1] (NA)
Coughing: C31D1 (n=7, 0)	19.0 (17.8)	NA [3] (NA)
Coughing: C32D1 (n=6, 0)	16.7 (27.9)	NA [3] (NA)
Coughing: C33D1 (n=6, 0)	11.1 (17.2)	NA [3] (NA)
Coughing: C34D1 (n=5, 0)	20.0 (29.8)	NA [3] (NA)
Coughing: C35D1 (n=4, 0)	33.3 (47.1)	NA [3] (NA)
Coughing: C36D1 (n=1, 0)	33.3 [1] (NA)	NA [3] (NA)
Coughing: C37D1 (n=1, 0)	33.3 [1] (NA)	NA [1] (NA)
Coughing: EOT (n=49, 90)	25.9 (23.8)	37.4 (29.1)
Hemoptysis: Baseline (n=164, 162)	2.4 (9.5)	3.7 (12.3)
Hemoptysis: C2D1 (n=155, 132)	1.7 (7.4)	3.5 (12.5)
Hemoptysis: C3D1 (n=153, 106)	0.9 (5.3)	2.2 (8.3)
Hemoptysis: C4D1 (n=135, 91)	1.0 (5.7)	1.5 (6.9)
Hemoptysis: C5D1 (n=123, 74)	0.3 (3.0)	0.9 (5.4)
Hemoptysis: C6D1 (n=119, 70)	0.6 (4.3)	3.8 (14.5)
Hemoptysis: C7D1 (n=115, 52)	0.0 (0.0)	1.3 (9.2)
Hemoptysis: C8D1 (n=111, 43)	0.9 (7.0)	2.3 (11.3)
Hemoptysis: C9D1 (n=101, 37)	0.3 (3.3)	2.7 (12.1)
Hemoptysis: C10D1 (n=94, 33)	0.4 (3.4)	3.0 (17.4)
Hemoptysis: C11D1 (n=83, 25)	2.4 (11.4)	4.0 (14.7)
Hemoptysis: C12D1 (n=76, 23)	0.9 (5.4)	5.8 (21.7)
Hemoptysis: C13D1 (n=74, 21)	2.3 (10.1)	4.8 (15.9)
Hemoptysis: C14D1 (n=66, 19)	0.5 (4.1)	0.0 (0.0)
Hemoptysis: C15D1 (n=62, 16)	1.1 (5.9)	0.0 (0.0)
Hemoptysis: C16D1 (n=53, 12)	0.6 (4.6)	5.6 (13.0)
Hemoptysis: C17D1 (n=47, 11)	0.0 (0.0)	9.1 (21.6)
Hemoptysis: C18D1 (n=45, 11)	1.5 (6.9)	3.0 (10.1)
Hemoptysis: C19D1 (n=40, 9)	0.0 (0.0)	3.7 (11.1)
Hemoptysis: C20D1 (n=35, 8)	1.0 (5.6)	8.3 (15.4)
Hemoptysis: C21D1 (n=30, 8)	0.0 (0.0)	4.2 (11.8)
Hemoptysis: C22D1 (n=24, 7)	0.0 (0.0)	9.5 (16.3)
Hemoptysis: C23D1 (n=23, 4)	1.4 (7.0)	0.0 (0.0)
Hemoptysis: C24D1 (n=20, 3)	0.0 (0.0)	0.0 (0.0)
Hemoptysis: C25D1 (n=18, 3)	0.0 (0.0)	0.0 (0.0)
Hemoptysis: C26D1 (n=14, 3)	0.0 (0.0)	0.0 (0.0)
Hemoptysis: C27D1 (n=14, 2)	0.0 (0.0)	0.0 (0.0)
Hemoptysis: C28D1 (n=11, 2)	0.0 (0.0)	0.0 (0.0)
Hemoptysis: C29D1 (n=8, 2)	0.0 (0.0)	0.0 (0.0)
Hemoptysis: C30D1 (n=8, 1)	0.0 (0.0)	0.0 [1] (NA)
Hemoptysis: C31D1 (n=7, 0)	0.0 (0.0)	NA [3] (NA)
Hemoptysis: C32D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Hemoptysis: C33D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Hemoptysis: C34D1 (n=5, 0)	0.0 (0.0)	NA [3] (NA)
Hemoptysis: C35D1 (n=4, 0)	0.0 (0.0)	NA [3] (NA)
Hemoptysis: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Hemoptysis: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Hemoptysis: EOT (n=49, 90)	0.7 (4.8)	4.8 (13.7)
Sore Mouth: Baseline (n=164, 162)	5.5 (15.3)	6.4 (18.4)
Sore Mouth: C2D1 (n=155, 132)	8.0 (17.9)	9.1 (18.5)
Sore Mouth: C3D1 (n=153, 106)	7.0 (14.6)	9.4 (21.0)
Sore Mouth: C4D1 (n=135, 91)	8.1 (16.5)	10.3 (21.5)
Sore Mouth: C5D1 (n=123, 73)	5.1 (12.1)	9.6 (20.4)
Sore Mouth: C6D1 (n=119, 70)	4.8 (13.9)	10.5 (19.3)
Sore Mouth: C7D1 (n=115, 52)	5.2 (15.0)	7.7 (15.6)
Sore Mouth: C8D1 (n=111, 43)	3.0 (9.6)	10.9 (18.9)
Sore Mouth: C9D1 (n=101, 37)	4.8 (12.5)	10.8 (22.3)
Sore Mouth: C10D1 (n=94, 33)	6.4 (14.9)	12.1 (23.3)
Sore Mouth: C11D1 (n=84, 25)	4.8 (14.8)	9.3 (18.1)
Sore Mouth: C12D1 (n=76, 23)	3.9 (12.1)	8.7 (18.0)
Sore Mouth: C13D1 (n=74, 21)	4.5 (12.7)	9.5 (15.4)
Sore Mouth: C14D1 (n=66, 19)	4.5 (12.9)	7.0 (14.0)
Sore Mouth: C15D1 (n=62, 16)	5.4 (12.4)	14.6 (29.7)
Sore Mouth: C16D1 (n=53, 12)	6.3 (14.7)	8.3 (15.1)
Sore Mouth: C17D1 (n=47, 11)	3.5 (10.4)	6.1 (13.5)
Sore Mouth: C18D1 (n=45, 11)	5.2 (12.2)	12.1 (16.8)
Sore Mouth: C19D1 (n=40, 9)	4.2 (11.2)	7.4 (14.7)
Sore Mouth: C20D1 (n=35, 8)	7.6 (16.3)	12.5 (24.8)
Sore Mouth: C21D1 (n=30, 8)	4.4 (11.5)	4.2 (11.8)
Sore Mouth: C22D1 (n=24, 7)	5.6 (12.7)	7.1 (13.1)
Sore Mouth: C23D1 (n=23, 4)	5.1 (11.7)	16.7 (19.2)
Sore Mouth: C24D1 (n=20, 3)	6.7 (17.4)	0.0 (0.0)
Sore Mouth: C25D1 (n=18, 3)	0.0 (0.0)	0.0 (0.0)
Sore Mouth: C26D1 (n=14, 3)	4.8 (17.8)	11.1 (19.2)
Sore Mouth: C27D1 (n=14, 2)	7.1 (19.3)	16.7 (23.6)
Sore Mouth: C28D1 (n=11, 2)	6.1 (20.1)	0.0 (0.0)
Sore Mouth: C29D1 (n=8, 2)	8.3 (15.4)	16.7 (23.6)
Sore Mouth: C30D1 (n=8, 1)	8.3 (23.6)	0.0 [1] (NA)
Sore Mouth: C31D1 (n=7, 0)	9.5 (25.2)	NA [3] (NA)
Sore Mouth: C32D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Sore Mouth: C33D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Sore Mouth: C34D1 (n=5, 0)	0.0 (0.0)	NA [3] (NA)
Sore Mouth: C35D1 (n=4, 0)	0.0 (0.0)	NA [3] (NA)
Sore Mouth: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Sore Mouth: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Sore Mouth: EOT (n=49, 90)	3.4 (10.2)	8.1 (18.2)
Dysphagia: Baseline (n=164, 162)	7.1 (16.4)	8.6 (20.9)
Dysphagia: C2D1 (n=155, 132)	8.2 (15.4)	9.8 (19.2)
Dysphagia: C3D1 (n=153, 106)	7.6 (16.4)	9.7 (20.6)
Dysphagia: C4D1 (n=135, 91)	6.2 (15.3)	8.1 (19.5)
Dysphagia: C5D1 (n=123, 74)	6.0 (14.8)	7.7 (17.0)
Dysphagia: C6D1 (n=119, 70)	7.0 (15.0)	10.0 (16.4)
Dysphagia: C7D1 (n=115, 52)	4.1 (11.8)	5.1 (13.8)
Dysphagia: C8D1 (n=111, 43)	3.2 (11.1)	6.2 (15.0)
Dysphagia: C9D1 (n=101, 37)	5.0 (11.9)	7.2 (16.0)
Dysphagia: C10D1 (n=94, 33)	4.3 (12.2)	6.1 (13.1)
Dysphagia: C11D1 (n=84, 25)	3.2 (9.8)	4.0 (11.1)
Dysphagia: C12D1 (n=76, 23)	3.5 (10.3)	7.2 (17.3)
Dysphagia: C13D1 (n=74, 21)	4.1 (11.0)	6.3 (13.4)
Dysphagia: C14D1 (n=66, 19)	3.0 (11.3)	7.0 (14.0)
Dysphagia: C15D1 (n=62, 16)	3.8 (13.6)	4.2 (16.7)
Dysphagia: C16D1 (n=53, 12)	4.4 (11.4)	2.8 (9.6)
Dysphagia: C17D1 (n=47, 11)	2.8 (9.4)	6.1 (13.5)
Dysphagia: C18D1 (n=45, 11)	3.7 (10.6)	3.0 (10.1)
Dysphagia: C19D1 (n=40, 9)	4.2 (11.2)	0.0 (0.0)
Dysphagia: C20D1 (n=35, 8)	4.8 (14.3)	8.3 (15.4)
Dysphagia: C21D1 (n=30, 8)	3.3 (10.2)	8.3 (15.4)
Dysphagia: C22D1 (n=24, 7)	2.8 (9.4)	0.0 (0.0)
Dysphagia: C23D1 (n=23, 4)	2.9 (9.6)	8.3 (16.7)
Dysphagia: C24D1 (n=20, 3)	5.0 (22.4)	0.0 (0.0)
Dysphagia: C25D1 (n=18, 3)	0.0 (0.0)	11.1 (19.2)
Dysphagia: C26D1 (n=14, 3)	9.5 (27.5)	11.1 (19.2)
Dysphagia: C27D1 (n=14, 2)	2.4 (8.9)	16.7 (23.6)
Dysphagia: C28D1 (n=11, 2)	6.1 (13.5)	16.7 (23.6)
Dysphagia: C29D1 (n=8, 2)	8.3 (15.4)	16.7 (23.6)
Dysphagia: C30D1 (n=8, 1)	0.0 (0.0)	33.3 [1] (NA)
Dysphagia: C31D1 (n=7, 0)	4.8 (12.6)	NA [3] (NA)
Dysphagia: C32D1 (n=6, 0)	5.6 (13.6)	NA [3] (NA)
Dysphagia: C33D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Dysphagia: C34D1 (n=5, 0)	6.7 (14.9)	NA [3] (NA)
Dysphagia: C35D1 (n=4, 0)	8.3 (16.7)	NA [3] (NA)
Dysphagia: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Dysphagia: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Dysphagia: EOT (n=49, 90)	4.8 (13.6)	8.5 (19.7)
Peripheral Neuropathy: Baseline (n=164, 162)	14.0 (22.1)	17.7 (27.3)
Peripheral Neuropathy: C2D1 (n=155, 132)	18.1 (24.1)	21.5 (29.2)
Peripheral Neuropathy: C3D1 (n=153, 106)	17.6 (26.2)	18.2 (29.1)
Peripheral Neuropathy: C4D1 (n=134, 91)	15.9 (23.0)	21.6 (27.8)
Peripheral Neuropathy: C5D1 (n=123, 74)	15.2 (21.0)	21.2 (28.4)
Peripheral Neuropathy: C6D1 (n=119, 70)	13.7 (21.9)	18.1 (27.0)
Peripheral Neuropathy: C7D1 (n=115, 52)	13.0 (21.0)	21.8 (28.7)
Peripheral Neuropathy: C8D1 (n=111, 43)	10.8 (20.2)	24.0 (32.8)
Peripheral Neuropathy: C9D1 (n=101, 37)	11.2 (19.6)	29.7 (34.1)
Peripheral Neuropathy: C10D1 (n=94, 33)	11.3 (21.1)	27.3 (29.4)
Peripheral Neuropathy: C11D1 (n=84, 25)	11.1 (21.5)	24.0 (31.2)
Peripheral Neuropathy: C12D1 (n=76, 23)	11.4 (22.1)	33.3 (36.2)
Peripheral Neuropathy: C13D1 (n=74, 21)	10.4 (19.1)	33.3 (35.0)
Peripheral Neuropathy: C14D1 (n=66, 19)	10.6 (21.2)	29.8 (35.0)
Peripheral Neuropathy: C15D1 (n=62, 16)	8.6 (18.0)	25.0 (31.0)
Peripheral Neuropathy: C16D1 (n=52, 12)	10.3 (19.3)	25.0 (20.7)
Peripheral Neuropathy: C17D1 (n=47, 11)	12.1 (23.5)	27.3 (29.1)
Peripheral Neuropathy: C18D1 (n=45, 11)	11.9 (22.6)	30.3 (31.5)
Peripheral Neuropathy: C19D1 (n=40, 9)	9.2 (20.0)	22.2 (16.7)
Peripheral Neuropathy: C20D1 (n=35, 8)	12.4 (25.7)	33.3 (30.9)
Peripheral Neuropathy: C21D1 (n=30, 8)	11.1 (18.2)	29.2 (21.4)
Peripheral Neuropathy: C22D1 (n=24, 7)	8.3 (20.3)	28.6 (23.0)
Peripheral Neuropathy: C23D1 (n=23, 4)	8.7 (20.6)	41.7 (31.9)
Peripheral Neuropathy: C24D1 (n=20, 3)	3.3 (14.9)	44.4 (38.5)
Peripheral Neuropathy: C25D1 (n=18, 3)	9.3 (19.2)	44.4 (38.5)
Peripheral Neuropathy: C26D1 (n=14, 3)	16.7 (36.4)	22.2 (19.2)
Peripheral Neuropathy: C27D1 (n=14, 2)	9.5 (20.4)	66.7 (0.0)
Peripheral Neuropathy: C28D1 (n=11, 2)	15.2 (22.9)	33.3 (0.0)
Peripheral Neuropathy: C29D1 (n=8, 2)	12.5 (24.8)	50.0 (23.6)
Peripheral Neuropathy: C30D1 (n=8, 1)	16.7 (30.9)	33.3 [1] (NA)
Peripheral Neuropathy: C31D1 (n=7, 0)	19.0 (32.5)	NA [3] (NA)
Peripheral Neuropathy: C32D1 (n=6, 0)	11.1 (27.2)	NA [3] (NA)
Peripheral Neuropathy: C33D1 (n=6, 0)	11.1 (27.2)	NA [3] (NA)
Peripheral Neuropathy: C34D1 (n=5, 0)	20.0 (44.7)	NA [3] (NA)
Peripheral Neuropathy: C35D1 (n=4, 0)	25.0 (50.0)	NA [3] (NA)
Peripheral Neuropathy: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Peripheral Neuropathy: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Peripheral Neuropathy: EOT (n=49, 90)	10.2 (16.9)	21.9 (29.6)
Alopecia: Baseline (n=163, 162)	17.4 (30.6)	16.9 (29.8)
Alopecia: C2D1 (n=155, 132)	9.5 (21.4)	36.6 (39.7)
Alopecia: C3D1 (n=153, 106)	7.6 (18.1)	30.5 (36.5)
Alopecia: C4D1 (n=135, 91)	8.9 (22.0)	24.9 (32.0)
Alopecia: C5D1 (n=123, 74)	6.0 (17.1)	23.9 (31.0)
Alopecia: C6D1 (n=118, 70)	4.2 (14.8)	23.3 (32.8)
Alopecia: C7D1 (n=115, 52)	4.9 (14.1)	19.9 (30.4)
Alopecia: C8D1 (n=111, 43)	3.9 (11.7)	18.6 (28.5)
Alopecia: C9D1 (n=101, 37)	4.0 (11.8)	16.2 (23.1)
Alopecia: C10D1 (n=94, 33)	4.6 (14.3)	14.1 (22.1)
Alopecia: C11D1 (n=84, 25)	4.0 (15.0)	16.0 (21.8)
Alopecia: C12D1 (n=76, 23)	4.4 (14.7)	20.3 (26.1)
Alopecia: C13D1 (n=74, 21)	6.3 (18.0)	12.7 (19.7)
Alopecia: C14D1 (n=65, 19)	3.6 (14.6)	15.8 (23.2)
Alopecia: C15D1 (n=62, 16)	4.8 (16.9)	8.3 (19.2)
Alopecia: C16D1 (n=53, 12)	6.3 (18.6)	13.9 (22.3)
Alopecia: C17D1 (n=46, 11)	5.1 (17.2)	18.2 (22.9)
Alopecia: C18D1 (n=45, 11)	3.7 (12.8)	18.2 (22.9)
Alopecia: C19D1 (n=40, 9)	5.8 (19.8)	18.5 (24.2)
Alopecia: C20D1 (n=35, 8)	3.8 (13.5)	25.0 (23.6)
Alopecia: C21D1 (n=30, 8)	7.8 (22.6)	16.7 (25.2)
Alopecia: C22D1 (n=24, 7)	2.8 (9.4)	14.3 (17.8)
Alopecia: C23D1 (n=23, 3)	1.4 (7.0)	22.2 (19.2)
Alopecia: C24D1 (n=20, 3)	6.7 (23.2)	33.3 (33.3)
Alopecia: C25D1 (n=18, 3)	9.3 (27.5)	33.3 (33.3)
Alopecia: C26D1 (n=14, 3)	7.1 (26.7)	44.4 (38.5)
Alopecia: C27D1 (n=14, 2)	16.7 (36.4)	33.3 (0.0)
Alopecia: C28D1 (n=11, 2)	6.1 (20.1)	50.0 (23.6)
Alopecia: C29D1 (n=8, 2)	16.7 (35.6)	33.3 (0.0)
Alopecia: C30D1 (n=8, 1)	12.5 (35.4)	33.3 [1] (NA)
Alopecia: C31D1 (n=7, 0)	9.5 (25.2)	NA [3] (NA)
Alopecia: C32D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Alopecia: C33D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Alopecia: C34D1 (n=5, 0)	0.0 (0.0)	NA [3] (NA)
Alopecia: C35D1 (n=4, 0)	0.0 (0.0)	NA [3] (NA)
Alopecia: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Alopecia: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Alopecia: EOT (n=49, 90)	6.8 (18.0)	33.3 (37.7)
Pain in Chest: Baseline (n=163, 160)	18.8 (22.8)	24.0 (27.5)
Pain in Chest: C2D1 (n=155, 132)	9.5 (17.7)	23.7 (25.9)
Pain in Chest: C3D1 (n=153, 106)	7.0 (13.6)	23.3 (26.5)
Pain in Chest: C4D1 (n=135, 91)	7.4 (13.9)	19.8 (22.8)
Pain in Chest: C5D1 (n=123, 74)	6.8 (14.1)	17.1 (21.5)
Pain in Chest: C6D1 (n=119, 70)	6.2 (13.0)	16.2 (22.5)
Pain in Chest: C7D1 (n=115, 52)	7.5 (14.7)	16.7 (22.4)
Pain in Chest: C8D1 (n=111, 43)	5.1 (14.4)	14.0 (20.9)
Pain in Chest: C9D1 (n=101, 37)	5.9 (12.8)	17.1 (23.1)
Pain in Chest: C10D1 (n=94, 33)	6.7 (14.3)	18.2 (31.3)
Pain in Chest: C11D1 (n=84, 25)	6.3 (13.2)	20.0 (25.5)
Pain in Chest: C12D1 (n=76, 23)	5.3 (12.2)	23.2 (30.9)
Pain in Chest: C13D1 (n=74, 21)	6.3 (13.1)	23.8 (30.1)
Pain in Chest: C14D1 (n=66, 19)	7.6 (16.3)	22.8 (22.4)
Pain in Chest: C15D1 (n=62, 16)	5.9 (14.2)	18.7 (24.2)
Pain in Chest: C16D1 (n=53, 12)	3.8 (10.7)	16.7 (17.4)
Pain in Chest: C17D1 (n=46, 11)	7.2 (15.6)	21.2 (22.5)
Pain in Chest: C18D1 (n=45, 11)	5.9 (16.3)	24.2 (33.6)
Pain in Chest: C19D1 (n=40, 9)	5.0 (14.2)	18.5 (24.2)
Pain in Chest: C20D1 (n=35, 8)	5.7 (15.1)	29.2 (21.4)
Pain in Chest: C21D1 (n=30, 8)	5.6 (15.4)	25.0 (23.6)
Pain in Chest: C22D1 (n=24, 7)	4.2 (11.3)	26.2 (30.2)
Pain in Chest: C23D1 (n=23, 4)	3.6 (10.0)	41.7 (31.9)
Pain in Chest: C24D1 (n=20, 3)	1.7 (7.5)	33.3 (33.3)
Pain in Chest: C25D1 (n=18, 3)	5.6 (12.8)	33.3 (33.3)
Pain in Chest: C26D1 (n=14, 3)	7.1 (19.3)	33.3 (33.3)
Pain in Chest: C27D1 (n=14, 2)	4.8 (12.1)	50.0 (23.6)
Pain in Chest: C28D1 (n=11, 2)	9.1 (15.6)	50.0 (23.6)
Pain in Chest: C29D1 (n=8, 2)	0.0 (0.0)	50.0 (23.6)
Pain in Chest: C30D1 (n=8, 1)	4.2 (11.8)	66.7 [1] (NA)
Pain in Chest: C31D1 (n=7, 0)	9.5 (16.3)	NA [3] (NA)
Pain in Chest: C32D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Pain in Chest: C33D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Pain in Chest: C34D1 (n=5, 0)	6.7 (14.9)	NA [3] (NA)
Pain in Chest: C35D1 (n=4, 0)	8.3 (16.7)	NA [3] (NA)
Pain in Chest: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Pain in Chest: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Pain in Chest: EOT (n=49, 90)	17.0 (24.6)	28.5 (29.4)
Pain in Arm or Shoulder: Baseline (n=164, 161)	16.3 (24.1)	19.5 (28.0)
Pain in Arm or Shoulder: C2D1 (n=155, 132)	9.0 (18.3)	19.9 (27.0)
Pain in Arm or Shoulder: C3D1 (n=153, 105)	8.1 (14.8)	17.5 (24.5)
Pain in Arm or Shoulder: C4D1 (n=135, 91)	6.9 (15.3)	14.3 (22.3)
Pain in Arm or Shoulder: C5D1 (n=123, 74)	6.2 (15.0)	13.1 (21.9)
Pain in Arm or Shoulder: C6D1 (n=119, 70)	6.7 (14.1)	17.1 (25.8)
Pain in Arm or Shoulder: C7D1 (n=115, 52)	6.4 (13.2)	17.3 (23.3)
Pain in Arm or Shoulder: C8D1 (n=111, 43)	6.9 (14.3)	20.2 (28.3)
Pain in Arm or Shoulder: C9D1 (n=101, 37)	5.6 (12.5)	23.4 (28.2)
Pain in Arm or Shoulder: C10D1 (n=94, 33)	7.4 (17.0)	25.3 (32.3)
Pain in Arm or Shoulder: C11D1 (n=84, 25)	6.0 (14.8)	24.0 (26.4)
Pain in Arm or Shoulder: C12D1 (n=76, 23)	6.6 (15.4)	29.0 (35.3)
Pain in Arm or Shoulder: C13D1 (n=74, 21)	5.9 (12.8)	25.4 (34.8)
Pain in Arm or Shoulder: C14D1 (n=66, 19)	7.6 (18.3)	29.8 (31.2)
Pain in Arm or Shoulder: C15D1 (n=62, 16)	5.4 (13.8)	25.0 (25.8)
Pain in Arm or Shoulder: C16D1 (n=53, 12)	5.0 (12.0)	16.7 (22.5)
Pain in Arm or Shoulder: C17D1 (n=47, 11)	3.5 (10.4)	21.2 (22.5)
Pain in Arm or Shoulder: C18D1 (n=45, 11)	8.1 (20.3)	30.3 (34.8)
Pain in Arm or Shoulder: C19D1 (n=40, 9)	6.7 (15.5)	18.5 (24.2)
Pain in Arm or Shoulder: C20D1 (n=35, 8)	9.5 (22.2)	25.0 (23.6)
Pain in Arm or Shoulder: C21D1 (n=30, 8)	7.8 (16.8)	29.2 (27.8)
Pain in Arm or Shoulder: C22D1 (n=24, 7)	2.8 (9.4)	21.4 (24.9)
Pain in Arm or Shoulder: C23D1 (n=23, 4)	0.7 (3.5)	33.3 (38.5)
Pain in Arm or Shoulder: C24D1 (n=20, 3)	3.3 (10.3)	44.4 (38.5)
Pain in Arm or Shoulder: C25D1 (n=18, 3)	1.9 (7.9)	33.3 (33.3)
Pain in Arm or Shoulder: C26D1 (n=14, 3)	7.1 (19.3)	22.2 (19.2)
Pain in Arm or Shoulder: C27D1 (n=14, 2)	4.8 (12.1)	50.0 (23.6)
Pain in Arm or Shoulder: C28D1 (n=11, 2)	0.0 (0.0)	33.3 (0.0)
Pain in Arm or Shoulder: C29D1 (n=8, 2)	0.0 (0.0)	66.7 (0.0)
Pain in Arm or Shoulder: C30D1 (n=8, 1)	0.0 (0.0)	33.3 [1] (NA)
Pain in Arm or Shoulder: C31D1 (n=7, 0)	0.0 (0.0)	NA [3] (NA)
Pain in Arm or Shoulder: C32D1 (n=6, 0)	11.1 (17.2)	NA [3] (NA)
Pain in Arm or Shoulder: C33D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Pain in Arm or Shoulder: C34D1 (n=5, 0)	0.0 (0.0)	NA [3] (NA)
Pain in Arm or Shoulder: C35D1 (n=4, 0)	0.0 (0.0)	NA [3] (NA)
Pain in Arm or Shoulder: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Pain in Arm or Shoulder: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Pain in Arm or Shoulder: EOT (n=48, 90)	11.1 (21.0)	21.9 (28.8)
Pain in Other Parts: Baseline (n=163, 158)	23.1 (27.3)	31.4 (30.4)
Pain in Other Parts: C2D1 (n=153, 125)	15.0 (23.2)	25.9 (28.0)
Pain in Other Parts: C3D1 (n=152, 104)	11.4 (20.7)	21.2 (27.1)
Pain in Other Parts: C4D1 (n=134, 90)	12.7 (22.7)	21.5 (24.6)
Pain in Other Parts: C5D1 (n=123, 73)	14.4 (23.0)	20.5 (27.6)
Pain in Other Parts: C6D1 (n=118, 68)	10.7 (18.9)	18.1 (26.0)
Pain in Other Parts: C7D1 (n=115, 51)	11.3 (20.7)	16.3 (26.1)
Pain in Other Parts: C8D1 (n=111, 42)	10.5 (20.6)	22.2 (30.9)
Pain in Other Parts: C9D1 (n=100, 37)	10.7 (21.1)	24.3 (31.1)
Pain in Other Parts: C10D1 (n=92, 33)	9.8 (18.8)	28.3 (35.5)
Pain in Other Parts: C11D1 (n=83, 25)	12.4 (21.3)	24.0 (29.7)
Pain in Other Parts: C12D1 (n=74, 23)	12.2 (20.3)	24.6 (30.5)
Pain in Other Parts: C13D1 (n=74, 21)	10.8 (19.2)	31.7 (34.1)
Pain in Other Parts: C14D1 (n=66, 19)	11.6 (18.0)	24.6 (29.1)
Pain in Other Parts: C15D1 (n=61, 16)	9.8 (15.3)	25.0 (22.8)
Pain in Other Parts: C16D1 (n=53, 12)	10.7 (19.4)	38.9 (34.3)
Pain in Other Parts: C17D1 (n=46, 11)	13.8 (19.3)	24.2 (21.6)
Pain in Other Parts: C18D1 (n=45, 11)	10.4 (19.9)	33.3 (39.4)
Pain in Other Parts: C19D1 (n=40, 9)	14.2 (22.5)	25.9 (14.7)
Pain in Other Parts: C20D1 (n=35, 8)	13.3 (20.1)	29.2 (21.4)
Pain in Other Parts: C21D1 (n=30, 8)	21.1 (27.0)	29.2 (37.5)
Pain in Other Parts: C22D1 (n=24, 7)	12.5 (21.6)	40.5 (30.2)
Pain in Other Parts: C23D1 (n=23, 4)	5.1 (11.7)	41.7 (31.9)
Pain in Other Parts: C24D1 (n=20, 3)	6.7 (17.4)	11.1 (19.2)
Pain in Other Parts: C25D1 (n=18, 3)	9.3 (15.4)	44.4 (38.5)
Pain in Other Parts: C26D1 (n=14, 3)	23.8 (30.5)	33.3 (33.3)
Pain in Other Parts: C27D1 (n=14, 2)	16.7 (31.4)	50.0 (23.6)
Pain in Other Parts: C28D1 (n=11, 2)	6.1 (13.5)	33.3 (0.0)
Pain in Other Parts: C29D1 (n=8, 2)	4.2 (11.8)	16.7 (23.6)
Pain in Other Parts: C30D1 (n=8, 1)	12.5 (17.3)	33.3 [1] (NA)
Pain in Other Parts: C31D1 (n=7, 0)	9.5 (16.3)	NA [3] (NA)
Pain in Other Parts: C32D1 (n=6, 0)	5.6 (13.6)	NA [3] (NA)
Pain in Other Parts: C33D1 (n=6, 0)	0.0 (0.0)	NA [3] (NA)
Pain in Other Parts: C34D1 (n=5, 0)	6.7 (14.9)	NA [3] (NA)
Pain in Other Parts: C35D1 (n=4, 0)	0.0 (0.0)	NA [3] (NA)
Pain in Other Parts: C36D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Pain in Other Parts: C37D1 (n=1, 0)	0.0 [1] (NA)	NA [3] (NA)
Pain in Other Parts: EOT (n=49, 90)	18.4 (29.7)	29.6 (34.8)

[1]

Standard deviation was not estimable since only one participant was evaluable.

[2]

Data was not analyzed as no participants were evaluable

[3]

Data was not analyzed as no participants were evaluable.

15. Secondary Outcome

Title	European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)
Description	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time Frame	Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks)

Outcome Measure Data

Analysis Population Description

FAS included all participants who were randomized to study treatment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants who were evaluable for specified time points for each arm group, respectively.

Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description:	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Number of Participants Analyzed	164	161
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline (n=164, 161)	64.09 (21.04)	66.76 (20.74)
C2D1 (n=153, 131)	69.19 (19.42)	66.33 (20.30)
C3D1 (n=153, 105)	73.13 (18.97)	65.84 (20.80)
C4D1 (n=135, 90)	73.78 (18.25)	69.13 (18.14)
C5D1 (n=122, 74)	75.27 (17.99)	68.12 (23.19)
C6D1 (n=120, 70)	75.79 (18.67)	69.71 (22.46)
C7D1 (n=115, 52)	77.02 (17.34)	70.63 (24.31)
C8D1 (n=110, 43)	74.72 (18.09)	72.30 (23.54)
C9D1 (n=101, 37)	74.45 (18.32)	72.27 (25.85)
C10D1 (n=94, 33)	75.49 (18.18)	74.27 (24.88)
C11D1 (n=84, 25)	76.32 (17.00)	77.24 (20.31)
C12D1 (n=77, 23)	76.95 (17.63)	74.83 (22.60)
C13D1 (n=73, 21)	76.38 (17.50)	73.00 (23.54)
C14D1 (n=66, 19)	78.77 (15.54)	74.11 (22.56)
C15D1 (n=62, 16)	77.71 (16.78)	77.44 (19.52)
C16D1 (n=53, 12)	75.32 (16.21)	79.00 (13.28)
C17D1 (n=47, 11)	75.09 (17.68)	81.73 (15.98)
C18D1 (n=45, 11)	75.87 (16.63)	78.91 (16.25)
C19D1 (n=40, 9)	76.85 (16.39)	78.00 (14.04)
C20D1 (n=35, 8)	72.66 (19.81)	76.75 (17.65)
C21D1 (n=30, 8)	74.13 (16.19)	73.63 (19.41)
C22D1 (n=24, 7)	77.54 (17.54)	72.21 (19.79)
C23D1 (n=23, 4)	75.48 (17.75)	54.00 (16.35)
C24D1 (n=20, 3)	71.40 (23.15)	62.00 (20.30)
C25D1 (n=18, 3)	75.61 (15.97)	63.67 (22.59)
C26D1 (n=14, 3)	72.14 (20.71)	63.00 (17.52)
C27D1 (n=14, 2)	66.57 (16.96)	50.00 (14.14)
C28D1 (n=11, 2)	72.36 (12.72)	55.00 (21.21)
C29D1 (n=8, 2)	71.38 (12.28)	45.00 (14.14)
C30D1 (n=8, 1)	69.50 (17.00)	40.00 [1] (NA)
C31D1 (n=7, 0)	68.57 (16.76)	NA [2] (NA)
C32D1 (n=6, 0)	65.83 (19.41)	NA [2] (NA)
C33D1 (n=6, 0)	67.50 (20.34)	NA [2] (NA)
C34D1 (n=5, 0)	68.00 (20.80)	NA [2] (NA)
C35D1 (n=4, 0)	72.25 (14.84)	NA [2] (NA)
C36D1 (n=1, 0)	90.00 [1] (NA)	NA [2] (NA)
C37D1 (n=1, 0)	85.00 [1] (NA)	NA [2] (NA)
EOT (n=49, 90)	68.33 (21.25)	58.34 (23.71)

[1]

Standard deviation was not estimable since only one participant was evaluable

[2]

Data was not analyzed as no participants were evaluable

Adverse Events

Time Frame	Active reporting period is from the time of informed consent until at least 28 days after the last dose of study treatment.
Adverse Event Reporting Description	All causality (serious and non-serious) adverse events have been reported. Non-serious adverse events above the 5% threshold are reported herein.
Arm/Group Title	Crizotinib	Chemotherapy
Arm/Group Description	Crizotinib (PF-02341066) 250 mg (administered as two 100-mg tablets and one 50-mg tablet) orally twice daily continuously in 21-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.	Pemetrexed 500 mg/m^2 intravenous infusion over 10 minutes or docetaxel 75 mg/m^2 intravenous infusion over 1 hour on Day 1 of 21-day cycle, as per investigator discretion. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred.
All-Cause Mortality
	Crizotinib	Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Crizotinib	Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	80/172 (46.51%)	42/171 (24.56%)
Blood and lymphatic system disorders
Anaemia * 1	2/172 (1.16%)	2/171 (1.17%)
Febrile neutropenia * 1	1/172 (0.58%)	12/171 (7.02%)
Neutropenia * 1	2/172 (1.16%)	2/171 (1.17%)
Thrombocytopenia * 1	0/172 (0.00%)	1/171 (0.58%)
Lymphadenopathy * 1	1/172 (0.58%)	0/171 (0.00%)
Cardiac disorders
Arrhythmia * 1	1/172 (0.58%)	0/171 (0.00%)
Cardiac arrest * 1	1/172 (0.58%)	0/171 (0.00%)
Cardiac tamponade * 1	1/172 (0.58%)	1/171 (0.58%)
Pericardial effusion * 1	1/172 (0.58%)	2/171 (1.17%)
Supraventricular tachycardia * 1	0/172 (0.00%)	1/171 (0.58%)
Coronary artery disease * 1	1/172 (0.58%)	0/171 (0.00%)
Myocardial ischaemia * 1	1/172 (0.58%)	0/171 (0.00%)
Syncope * 1	1/172 (0.58%)	0/171 (0.00%)
Gastrointestinal disorders
Abdominal pain upper * 1	1/172 (0.58%)	0/171 (0.00%)
Diarrhoea * 1	1/172 (0.58%)	0/171 (0.00%)
Ileus paralytic * 1	1/172 (0.58%)	0/171 (0.00%)
Intestinal perforation * 1	1/172 (0.58%)	0/171 (0.00%)
Nausea * 1	1/172 (0.58%)	2/171 (1.17%)
Oesophageal stenosis * 1	1/172 (0.58%)	0/171 (0.00%)
Stomatitis * 1	0/172 (0.00%)	1/171 (0.58%)
Vomiting * 1	3/172 (1.74%)	0/171 (0.00%)
Food poisoning * 1	1/172 (0.58%)	0/171 (0.00%)
Haematemesis * 1	1/172 (0.58%)	0/171 (0.00%)
Melaena * 1	0/172 (0.00%)	1/171 (0.58%)
General disorders
Product contamination microbial * 1	0/172 (0.00%)	1/171 (0.58%)
Chest pain * 1	0/172 (0.00%)	2/171 (1.17%)
Death * 1	2/172 (1.16%)	0/171 (0.00%)
Disease progression * 1	18/172 (10.47%)	3/171 (1.75%)
Fatigue * 1	1/172 (0.58%)	1/171 (0.58%)
Mucosal inflammation * 1	0/172 (0.00%)	2/171 (1.17%)
Pyrexia * 1	1/172 (0.58%)	1/171 (0.58%)
Sudden death * 1	1/172 (0.58%)	0/171 (0.00%)
General physical health deterioration * 1	1/172 (0.58%)	0/171 (0.00%)
Malaise * 1	1/172 (0.58%)	0/171 (0.00%)
Hepatobiliary disorders
Hepatic failure * 1	1/172 (0.58%)	0/171 (0.00%)
Hepatitis * 1	1/172 (0.58%)	0/171 (0.00%)
Infections and infestations
Empyema * 1	1/172 (0.58%)	0/171 (0.00%)
Extradural abscess * 1	1/172 (0.58%)	0/171 (0.00%)
Lower respiratory tract infection * 1	2/172 (1.16%)	2/171 (1.17%)
Lung abscess * 1	2/172 (1.16%)	0/171 (0.00%)
Lung infection * 1	2/172 (1.16%)	1/171 (0.58%)
Pneumonia * 1	8/172 (4.65%)	3/171 (1.75%)
Pneumonia bacterial * 1	1/172 (0.58%)	0/171 (0.00%)
Sepsis * 1	1/172 (0.58%)	1/171 (0.58%)
Urinary tract infection * 1	0/172 (0.00%)	1/171 (0.58%)
Cellulitis * 1	2/172 (1.16%)	0/171 (0.00%)
Gastroenteritis * 1	1/172 (0.58%)	0/171 (0.00%)
Pneumonia influenzal * 1	1/172 (0.58%)	0/171 (0.00%)
Injury, poisoning and procedural complications
Femur fracture * 1	1/172 (0.58%)	1/171 (0.58%)
Spinal fracture * 1	1/172 (0.58%)	0/171 (0.00%)
Investigations
Alanine aminotransferase increased * 1	3/172 (1.74%)	0/171 (0.00%)
Aspartate aminotransferase increased * 1	2/172 (1.16%)	0/171 (0.00%)
Blood glucose increased * 1	1/172 (0.58%)	0/171 (0.00%)
Electrocardiogram QT prolonged * 1	1/172 (0.58%)	0/171 (0.00%)
Haemoglobin * 1	0/172 (0.00%)	1/171 (0.58%)
Neutrophil count decreased * 1	0/172 (0.00%)	1/171 (0.58%)
White blood cell count decreased * 1	0/172 (0.00%)	2/171 (1.17%)
Metabolism and nutrition disorders
Decreased appetite * 1	2/172 (1.16%)	1/171 (0.58%)
Hyperglycaemia * 1	1/172 (0.58%)	0/171 (0.00%)
Hyperkalaemia * 1	1/172 (0.58%)	0/171 (0.00%)
Hypoglycaemia * 1	2/172 (1.16%)	1/171 (0.58%)
Hypokalaemia * 1	1/172 (0.58%)	0/171 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain * 1	2/172 (1.16%)	2/171 (1.17%)
Muscular weakness * 1	1/172 (0.58%)	0/171 (0.00%)
Musculoskeletal pain * 1	0/172 (0.00%)	1/171 (0.58%)
Spinal column stenosis * 1	1/172 (0.58%)	0/171 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage * 1	0/172 (0.00%)	1/171 (0.58%)
Colon cancer * 1	0/172 (0.00%)	1/171 (0.58%)
Colon cancer recurrent * 1	0/172 (0.00%)	1/171 (0.58%)
Nervous system disorders
Brain oedema * 1	1/172 (0.58%)	0/171 (0.00%)
Headache * 1	1/172 (0.58%)	2/171 (1.17%)
Intracranial pressure increased * 1	2/172 (1.16%)	0/171 (0.00%)
Lethargy * 1	1/172 (0.58%)	0/171 (0.00%)
Paraesthesia * 1	1/172 (0.58%)	0/171 (0.00%)
Presyncope * 1	1/172 (0.58%)	0/171 (0.00%)
Cerebral cyst * 1	1/172 (0.58%)	0/171 (0.00%)
Dizziness * 1	1/172 (0.58%)	0/171 (0.00%)
Seizure * 1	2/172 (1.16%)	1/171 (0.58%)
Psychiatric disorders
Confusional state * 1	0/172 (0.00%)	1/171 (0.58%)
Mental status changes * 1	1/172 (0.58%)	0/171 (0.00%)
Delirium * 1	1/172 (0.58%)	0/171 (0.00%)
Renal and urinary disorders
Renal cyst * 1	1/172 (0.58%)	0/171 (0.00%)
Ureteric stenosis * 1	1/172 (0.58%)	0/171 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome * 1	1/172 (0.58%)	0/171 (0.00%)
Acute respiratory failure * 1	1/172 (0.58%)	0/171 (0.00%)
Cough * 1	1/172 (0.58%)	0/171 (0.00%)
Dyspnoea * 1	6/172 (3.49%)	2/171 (1.17%)
Interstitial lung disease * 1	3/172 (1.74%)	0/171 (0.00%)
Organising pneumonia * 1	0/172 (0.00%)	1/171 (0.58%)
Pleural effusion * 1	2/172 (1.16%)	3/171 (1.75%)
Pneumonitis * 1	1/172 (0.58%)	0/171 (0.00%)
Pulmonary artery thrombosis * 1	1/172 (0.58%)	0/171 (0.00%)
Pulmonary embolism * 1	7/172 (4.07%)	3/171 (1.75%)
Pulmonary oedema * 1	0/172 (0.00%)	1/171 (0.58%)
Respiratory failure * 1	1/172 (0.58%)	0/171 (0.00%)
Skin and subcutaneous tissue disorders
Drug eruption * 1	1/172 (0.58%)	0/171 (0.00%)
Surgical and medical procedures
Cancer surgery * 1	1/172 (0.58%)	0/171 (0.00%)
Vascular disorders
Deep vein thrombosis * 1	1/172 (0.58%)	2/171 (1.17%)
Pelvic venous thrombosis * 1	1/172 (0.58%)	0/171 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 18.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Crizotinib	Chemotherapy
	Affected / at Risk (%)	Affected / at Risk (%)
Total	172/172 (100.00%)	169/171 (98.83%)
Blood and lymphatic system disorders
Anaemia * 1	36/172 (20.93%)	27/171 (15.79%)
Leukopenia * 1	24/172 (13.95%)	9/171 (5.26%)
Neutropenia * 1	41/172 (23.84%)	18/171 (10.53%)
Cardiac disorders
Bradycardia * 1	9/172 (5.23%)	0/171 (0.00%)
Eye disorders
Photopsia * 1	21/172 (12.21%)	1/171 (0.58%)
Vision blurred * 1	13/172 (7.56%)	5/171 (2.92%)
Visual impairment * 1	74/172 (43.02%)	8/171 (4.68%)
Lacrimation increased * 1	1/172 (0.58%)	9/171 (5.26%)
Gastrointestinal disorders
Abdominal pain * 1	18/172 (10.47%)	8/171 (4.68%)
Abdominal pain upper * 1	17/172 (9.88%)	13/171 (7.60%)
Constipation * 1	83/172 (48.26%)	39/171 (22.81%)
Diarrhoea * 1	106/172 (61.63%)	34/171 (19.88%)
Dyspepsia * 1	18/172 (10.47%)	6/171 (3.51%)
Nausea * 1	104/172 (60.47%)	60/171 (35.09%)
Stomatitis * 1	9/172 (5.23%)	13/171 (7.60%)
Vomiting * 1	88/172 (51.16%)	32/171 (18.71%)
Dysphagia * 1	9/172 (5.23%)	2/171 (1.17%)
Gastrooesophageal reflux disease * 1	12/172 (6.98%)	0/171 (0.00%)
General disorders
Asthenia * 1	31/172 (18.02%)	32/171 (18.71%)
Chest pain * 1	15/172 (8.72%)	13/171 (7.60%)
Fatigue * 1	51/172 (29.65%)	60/171 (35.09%)
Oedema * 1	15/172 (8.72%)	6/171 (3.51%)
Oedema peripheral * 1	59/172 (34.30%)	15/171 (8.77%)
Pyrexia * 1	41/172 (23.84%)	33/171 (19.30%)
Pain * 1	10/172 (5.81%)	9/171 (5.26%)
Infections and infestations
Nasopharyngitis * 1	32/172 (18.60%)	7/171 (4.09%)
Upper respiratory tract infection * 1	24/172 (13.95%)	14/171 (8.19%)
Injury, poisoning and procedural complications
Fall * 1	11/172 (6.40%)	3/171 (1.75%)
Investigations
Alanine aminotransferase increased * 1	72/172 (41.86%)	21/171 (12.28%)
Aspartate aminotransferase increased * 1	55/172 (31.98%)	17/171 (9.94%)
Blood alkaline phosphatase increased * 1	18/172 (10.47%)	6/171 (3.51%)
Blood creatinine increased * 1	13/172 (7.56%)	3/171 (1.75%)
Neutrophil count decreased * 1	15/172 (8.72%)	9/171 (5.26%)
Weight decreased * 1	21/172 (12.21%)	8/171 (4.68%)
White blood cell count decreased * 1	16/172 (9.30%)	13/171 (7.60%)
Electrocardiogram QT prolonged * 1	9/172 (5.23%)	0/171 (0.00%)
Metabolism and nutrition disorders
Decreased appetite * 1	56/172 (32.56%)	46/171 (26.90%)
Hyperglycaemia * 1	12/172 (6.98%)	9/171 (5.26%)
Hypoalbuminaemia * 1	16/172 (9.30%)	1/171 (0.58%)
Hypokalaemia * 1	15/172 (8.72%)	5/171 (2.92%)
Hypocalcaemia * 1	13/172 (7.56%)	0/171 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	15/172 (8.72%)	20/171 (11.70%)
Back pain * 1	30/172 (17.44%)	11/171 (6.43%)
Musculoskeletal pain * 1	14/172 (8.14%)	6/171 (3.51%)
Myalgia * 1	5/172 (2.91%)	19/171 (11.11%)
Pain in extremity * 1	20/172 (11.63%)	10/171 (5.85%)
Muscle spasms * 1	9/172 (5.23%)	4/171 (2.34%)
Neck pain * 1	11/172 (6.40%)	5/171 (2.92%)
Nervous system disorders
Dizziness * 1	34/172 (19.77%)	13/171 (7.60%)
Dysgeusia * 1	45/172 (26.16%)	17/171 (9.94%)
Headache * 1	46/172 (26.74%)	26/171 (15.20%)
Neuropathy peripheral * 1	5/172 (2.91%)	10/171 (5.85%)
Paraesthesia * 1	13/172 (7.56%)	7/171 (4.09%)
Peripheral sensory neuropathy * 1	9/172 (5.23%)	6/171 (3.51%)
Visual perseveration * 1	12/172 (6.98%)	0/171 (0.00%)
Psychiatric disorders
Insomnia * 1	19/172 (11.05%)	13/171 (7.60%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	37/172 (21.51%)	35/171 (20.47%)
Dyspnoea * 1	27/172 (15.70%)	29/171 (16.96%)
Epistaxis * 1	3/172 (1.74%)	10/171 (5.85%)
Haemoptysis * 1	9/172 (5.23%)	11/171 (6.43%)
Oropharyngeal pain * 1	20/172 (11.63%)	7/171 (4.09%)
Rhinorrhoea * 1	4/172 (2.33%)	9/171 (5.26%)
Productive cough * 1	12/172 (6.98%)	8/171 (4.68%)
Pulmonary embolism * 1	9/172 (5.23%)	2/171 (1.17%)
Skin and subcutaneous tissue disorders
Alopecia * 1	21/172 (12.21%)	35/171 (20.47%)
Dry skin * 1	10/172 (5.81%)	2/171 (1.17%)
Pruritus * 1	12/172 (6.98%)	7/171 (4.09%)
Rash * 1	23/172 (13.37%)	30/171 (17.54%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 18.1

Limitations and Caveats

No analyses of ALK fusion variants or protein expression were done due to limited slide stability of unstained tissue sections required for immunohistochemistry and no nucleic acid based assay was available to identify specific ALK gene fusion.

More Information

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

• 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):

Camidge DR, Kim EE, Usari T, Polli A, Lewis I, Wilner KD. Renal Effects of Crizotinib in Patients With ALK-Positive Advanced NSCLC. J Thorac Oncol. 2019 Jun;14(6):1077-1085. doi: 10.1016/j.jtho.2019.02.015. Epub 2019 Feb 26.

Wilner KD, Usari T, Polli A, Kim EE. Comparison of cardiovascular effects of crizotinib and chemotherapy in ALK-positive advanced non-small-cell lung cancer. Future Oncol. 2019 Apr;15(10):1097-1103. doi: 10.2217/fon-2018-0869. Epub 2019 Jan 17.

Yoneda KY, Scranton JR, Cadogan MA, Tassell V, Nadanaciva S, Wilner KD, Stollenwerk NS. Interstitial Lung Disease Associated With Crizotinib in Patients With Advanced Non-Small Cell Lung Cancer: Independent Review of Four PROFILE Trials. Clin Lung Cancer. 2017 Sep;18(5):472-479. doi: 10.1016/j.cllc.2017.03.004. Epub 2017 Mar 14.

Lin YT, Yu CJ, Yang JC, Shih JY. Anaplastic Lymphoma Kinase (ALK) Kinase Domain Mutation Following ALK Inhibitor(s) Failure in Advanced ALK Positive Non-Small-Cell Lung Cancer: Analysis and Literature Review. Clin Lung Cancer. 2016 Sep;17(5):e77-e94. doi: 10.1016/j.cllc.2016.03.005. Epub 2016 Mar 30.

Costa DB, Shaw AT, Ou SH, Solomon BJ, Riely GJ, Ahn MJ, Zhou C, Shreeve SM, Selaru P, Polli A, Schnell P, Wilner KD, Wiltshire R, Camidge DR, Crino L. Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastases. J Clin Oncol. 2015 Jun 10;33(17):1881-8. doi: 10.1200/JCO.2014.59.0539. Epub 2015 Jan 26.

Lin YT, Wang YF, Yang JC, Yu CJ, Wu SG, Shih JY, Yang PC. Development of renal cysts after crizotinib treatment in advanced ALK-positive non-small-cell lung cancer. J Thorac Oncol. 2014 Nov;9(11):1720-5. doi: 10.1097/JTO.0000000000000326.

Shaw AT, Kim DW, Nakagawa K, Seto T, Crino L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Janne PA. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. doi: 10.1056/NEJMoa1214886. Epub 2013 Jun 1. Erratum In: N Engl J Med. 2015 Oct 15;373(16):1582.

Tamiya A, Okamoto I, Miyazaki M, Shimizu S, Kitaichi M, Nakagawa K. Severe acute interstitial lung disease after crizotinib therapy in a patient with EML4-ALK-positive non-small-cell lung cancer. J Clin Oncol. 2013 Jan 1;31(1):e15-7. doi: 10.1200/JCO.2012.43.3730. Epub 2012 Nov 19. No abstract available.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00932893
• Other Study ID Numbers: A8081007; 2009-012595-27 ( EudraCT Number )
• First Submitted: June 30, 2009
• First Posted: July 3, 2009
• Results First Submitted: March 13, 2013
• Results First Posted: June 6, 2013
• Last Update Posted: January 2, 2017