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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00932893
First received: June 30, 2009
Last updated: August 7, 2014
Last verified: August 2014
Results First Received: March 13, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Non-Small-Cell Lung
Interventions: Drug: PF-02341066
Drug: Pemetrexed
Drug: Docetaxel

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Crizotinib Crizotinib (PF-02341066) 250 milligram (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.
Chemotherapy 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.

Participant Flow:   Overall Study
    Crizotinib     Chemotherapy  
STARTED     173     174  
Treated     172     171  
COMPLETED     0     0  
NOT COMPLETED     173     174  
Death                 46                 16  
Lost to Follow-up                 1                 0  
Withdrawal by Subject                 3                 2  
Unspecified                 5                 107  
Ongoing at Data Cut-off                 118                 49  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS) included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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 Total of all reporting groups

Baseline Measures
    Crizotinib     Chemotherapy     Total  
Number of Participants  
[units: participants]
  173     174     347  
Age  
[units: years]
Mean ± Standard Deviation
  50.31  ± 13.1     49.81  ± 13.0     50.06  ± 13.0  
Gender  
[units: participants]
     
Female     98     96     194  
Male     75     78     153  



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Progression-Free Survival (PFS)   [ 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) ]

Measure Type Primary
Measure Title Progression-Free Survival (PFS)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set (FAS) included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  173     174  
Progression-Free Survival (PFS)  
[units: months]
Median ( 95% Confidence Interval )
  7.7  
  ( 6.0 to 8.8 )  
  3.0  
  ( 2.6 to 4.3 )  


Statistical Analysis 1 for Progression-Free Survival (PFS)
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.0001
Hazard Ratio (HR) [4] 0.487
95% Confidence Interval ( 0.371 to 0.638 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  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.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Overall Survival (OS)   [ Time Frame: Randomization until death (up to 112 weeks) ]

Measure Type Secondary
Measure Title Overall Survival (OS)
Measure 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 112 weeks)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  173     174  
Overall Survival (OS)  
[units: months]
Median ( 95% Confidence Interval )
  20.3  
  ( 18.1 to NA ) [1]
  22.8  
  ( 18.6 to NA ) [1]
[1] The upper limit of 95 percent (%) confidence interval (CI) was not reached at the time of data cut-off.


Statistical Analysis 1 for Overall Survival (OS)
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.5394
Hazard Ratio (HR) [4] 1.021
95% Confidence Interval ( 0.677 to 1.540 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance: 1-sided at alpha=0.0004.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Overall Survival Probability at Month 6 and Month 12   [ Time Frame: Month 6, 12 ]

Measure Type Secondary
Measure Title Overall Survival Probability at Month 6 and Month 12
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  173     174  
Overall Survival Probability at Month 6 and Month 12  
[units: percent chance of survival]
Number ( 95% Confidence Interval )
   
Month 6     86.8  
  ( 80.4 to 91.2 )  
  83.8  
  ( 77.0 to 88.7 )  
Month 12     69.5  
  ( 60.6 to 76.8 )  
  71.8  
  ( 63.3 to 78.7 )  

No statistical analysis provided for Overall Survival Probability at Month 6 and Month 12



4.  Secondary:   Percentage of Participants With Objective Response (OR)   [ 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) ]

Measure Type Secondary
Measure Title Percentage of Participants With Objective Response (OR)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  173     174  
Percentage of Participants With Objective Response (OR)  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  65.3  
  ( 57.7 to 72.4 )  
  19.5  
  ( 13.9 to 26.2 )  


Statistical Analysis 1 for Percentage of Participants With Objective Response (OR)
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.0001
Risk Ratio (RR) [4] 3.394
95% Confidence Interval ( 2.463 to 4.676 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance: 1-sided at alpha=0.025.
[4] Other relevant estimation information:
  No text entered.



5.  Secondary:   Percentage of Participants With Disease Control at Week 6   [ Time Frame: Week 6 ]

Measure Type Secondary
Measure Title Percentage of Participants With Disease Control at Week 6
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  173     174  
Percentage of Participants With Disease Control at Week 6  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  81.5  
  ( 74.9 to 87.0 )  
  55.2  
  ( 47.5 to 62.7 )  


Statistical Analysis 1 for Percentage of Participants With Disease Control at Week 6
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.0001
Risk Ratio (RR) [4] 1.502
95% Confidence Interval ( 1.297 to 1.741 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance: 1-sided at alpha=0.0004.
[4] Other relevant estimation information:
  No text entered.



6.  Secondary:   Percentage of Participants With Disease Control at Week 12   [ Time Frame: Week 12 ]

Measure Type Secondary
Measure Title Percentage of Participants With Disease Control at Week 12
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS included all participants who were randomized to study treatment.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  173     174  
Percentage of Participants With Disease Control at Week 12  
[units: percentage of participants]
Number ( 95% Confidence Interval )
  64.2  
  ( 56.5 to 71.3 )  
  38.5  
  ( 31.2 to 46.2 )  


Statistical Analysis 1 for Percentage of Participants With Disease Control at Week 12
Groups [1] All groups
Method [2] Cochran-Mantel-Haenszel
P Value [3] <0.0001
Risk Ratio (RR) [4] 1.697
95% Confidence Interval ( 1.368 to 2.103 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Statistical significance: 1-sided at alpha=0.0004.
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   Duration of Response (DR)   [ 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) ]

Measure Type Secondary
Measure Title Duration of Response (DR)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS included all participants who were randomized to study treatment. Here 'N' (number of participant analyzed) signifies participants with objective tumor response.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  113     34  
Duration of Response (DR)  
[units: weeks]
Median ( 95% Confidence Interval )
  36  
  ( 29.1 to 43.6 )  
  24.4  
  ( 15 to 36 )  

No statistical analysis provided for Duration of Response (DR)



8.  Secondary:   Time to Tumor Response (TTR)   [ 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) ]

Measure Type Secondary
Measure Title Time to Tumor Response (TTR)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS included all participants who were randomized to study treatment. Here 'N' (number of participant analyzed) signifies participants with objective tumor response.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  113     34  
Time to Tumor Response (TTR)  
[units: weeks]
Median ( Full Range )
  6.3  
  ( 4.4 to 48.4 )  
  12.6  
  ( 5 to 37.1 )  

No statistical analysis provided for Time to Tumor Response (TTR)



9.  Secondary:   Pre-Dose Plasma Concentration (Ctrough) of Crizotinib   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2, 3, 5 ]

Measure Type Secondary
Measure Title Pre-Dose Plasma Concentration (Ctrough) of Crizotinib
Measure Description 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, 3, 5  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Crizotinib 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.

Measured Values
    Crizotinib  
Number of Participants Analyzed  
[units: participants]
  62  
Pre-Dose Plasma Concentration (Ctrough) of Crizotinib  
[units: nanogram per milliliter (ng/mL)]
Geometric Mean ± Standard Deviation
 
Cycle 1 Day 1 (n=15)     NA  ± NA [1]
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).

No statistical analysis provided for Pre-Dose Plasma Concentration (Ctrough) of Crizotinib



10.  Secondary:   Pre-Dose Plasma Concentration at Steady State (Ctrough, ss) of Crizotinib   [ Time Frame: Pre-dose on Day 15 of Cycle 1 ]

Measure Type Secondary
Measure Title Pre-Dose Plasma Concentration at Steady State (Ctrough, ss) of Crizotinib
Measure Description Only participants receiving crizotinib were to be analyzed for this outcome measure as per planned analysis.
Time Frame Pre-dose on Day 15 of Cycle 1  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Crizotinib 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.

Measured Values
    Crizotinib  
Number of Participants Analyzed  
[units: participants]
  92  
Pre-Dose Plasma Concentration at Steady State (Ctrough, ss) of Crizotinib  
[units: ng/mL]
Geometric Mean ± Standard Deviation
  298  ± 148  

No statistical analysis provided for Pre-Dose Plasma Concentration at Steady State (Ctrough, ss) of Crizotinib



11.  Secondary:   Number of Participants With Categorical Maximum QTcF for Crizotinib   [ Time Frame: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 1, 2 ]

Measure Type Secondary
Measure Title Number of Participants With Categorical Maximum QTcF for Crizotinib
Measure 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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Crizotinib 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.

Measured Values
    Crizotinib  
Number of Participants Analyzed  
[units: participants]
  147  
Number of Participants With Categorical Maximum QTcF for Crizotinib  
[units: participants]
 
<450 msec     132  
450 msec to <480 msec     9  
480 msec to <500 msec     1  
>=500 msec     5  

No statistical analysis provided for Number of Participants With Categorical Maximum QTcF for Crizotinib



12.  Secondary:   Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough   [ Time Frame: Baseline up to end of treatment (up to 112 weeks) ]

Measure Type Secondary
Measure Title Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  162     151  
Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough  
[units: months]
Median ( 95% Confidence Interval )
  5.6  
  ( 3.4 to 11.0 )  
  1.4  
  ( 1.0 to 1.8 )  


Statistical Analysis 1 for Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.0001
Hazard Ratio (HR) [4] 0.535
95% Confidence Interval ( 0.404 to 0.709 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



13.  Secondary:   European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)   [ Time Frame: Baseline, Day (D) 1 of each cycle (C) until disease progression, end of treatment (EOT, up to 112 weeks) ]

Measure Type Secondary
Measure Title European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  165     163  
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)  
[units: units on a scale]
Mean ± Standard Deviation
   
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  ± NA [1]
Global QoL: C31D1 (n=7, 0)     64.3  ± 17.2     NA  ± NA [2]
Global QoL: C32D1 (n=6, 0)     59.7  ± 17.0     NA  ± NA [2]
Global QoL: C33D1 (n=6, 0)     66.7  ± 18.3     NA  ± NA [2]
Global QoL: C34D1 (n=5, 0)     68.3  ± 14.9     NA  ± NA [2]
Global QoL: C35D1 (n=4, 0)     60.4  ± 22.9     NA  ± NA [2]
Global QoL: C36D1 (n=1, 0)     66.7  ± NA [1]   NA  ± NA [2]
Global QoL: C37D1 (n=1, 0)     66.7  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Physical Functioning: C31D1 (n=7, 0)     83.8  ± 17.2     NA  ± NA [2]
Physical Functioning: C32D1 (n=6, 0)     88.9  ± 9.1     NA  ± NA [2]
Physical Functioning: C33D1 (n=6, 0)     90.0  ± 7.0     NA  ± NA [2]
Physical Functioning: C34D1 (n=5, 0)     85.3  ± 7.3     NA  ± NA [2]
Physical Functioning: C35D1 (n=4, 0)     91.7  ± 3.3     NA  ± NA [2]
Physical Functioning: C36D1 (n=1, 0)     86.7  ± NA [1]   NA  ± NA [2]
Physical Functioning: C37D1 (n=1, 0)     86.7  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Role Functioning: C31D1 (n=7, 0)     71.4  ± 36.9     NA  ± NA [2]
Role Functioning: C32D1 (n=6, 0)     86.1  ± 12.5     NA  ± NA [2]
Role Functioning: C33D1 (n=6, 0)     88.9  ± 13.6     NA  ± NA [2]
Role Functioning: C34D1 (n=5, 0)     96.7  ± 7.5     NA  ± NA [2]
Role Functioning: C35D1 (n=4, 0)     91.7  ± 16.7     NA  ± NA [2]
Role Functioning: C36D1 (n=1, 0)     100.0  ± NA [1]   NA  ± NA [2]
Role Functioning: C37D1 (n=1, 0)     100.0  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Emotional Functioning: C31D1 (n=7, 0)     76.2  ± 28.2     NA  ± NA [2]
Emotional Functioning: C32D1 (n=6, 0)     87.5  ± 17.3     NA  ± NA [2]
Emotional Functioning: C33D1 (n=6, 0)     90.3  ± 13.4     NA  ± NA [2]
Emotional Functioning: C34D1 (n=5, 0)     91.7  ± 14.4     NA  ± NA [2]
Emotional Functioning: C35D1 (n=4, 0)     83.3  ± 20.4     NA  ± NA [2]
Emotional Functioning: C36D1 (n=1, 0)     58.3  ± NA [1]   NA  ± NA [2]
Emotional Functioning: C37D1 (n=1, 0)     58.3  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Cognitive Functioning: C31D1 (n=7, 0)     81.0  ± 20.2     NA  ± NA [2]
Cognitive Functioning: C32D1 (n=6, 0)     83.3  ± 18.3     NA  ± NA [2]
Cognitive Functioning: C33D1 (n=6, 0)     86.1  ± 16.4     NA  ± NA [2]
Cognitive Functioning: C34D1 (n=5, 0)     90.0  ± 9.1     NA  ± NA [2]
Cognitive Functioning: C35D1 (n=4, 0)     95.8  ± 8.3     NA  ± NA [2]
Cognitive Functioning: C36D1 (n=1, 0)     100.0  ± NA [1]   NA  ± NA [2]
Cognitive Functioning: C37D1 (n=1, 0)     83.3  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Social Functioning: C31D1 (n=7, 0)     73.8  ± 38.3     NA  ± NA [2]
Social Functioning: C32D1 (n=6, 0)     83.3  ± 18.3     NA  ± NA [2]
Social Functioning: C33D1 (n=6, 0)     94.4  ± 13.6     NA  ± NA [2]
Social Functioning: C34D1 (n=5, 0)     96.7  ± 7.5     NA  ± NA [2]
Social Functioning: C35D1 (n=4, 0)     91.7  ± 16.7     NA  ± NA [2]
Social Functioning: C36D1 (n=1, 0)     66.7  ± NA [1]   NA  ± NA [2]
Social Functioning: C37D1 (n=1, 0)     66.7  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Fatigue: C31D1 (n=7, 0)     28.6  ± 16.8     NA  ± NA [2]
Fatigue: C32D1 (n=6, 0)     25.9  ± 5.7     NA  ± NA [1]
Fatigue: C33D1 (n=6, 0)     18.5  ± 11.5     NA  ± NA [2]
Fatigue: C34D1 (n=5, 0)     15.6  ± 16.9     NA  ± NA [2]
Fatigue: C35D1 (n=4, 0)     27.8  ± 14.3     NA  ± NA [2]
Fatigue: C36D1 (n=1, 0)     33.3  ± NA [1]   NA  ± NA [2]
Fatigue: C37D1 (n=1, 0)     11.1  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Nausea and Vomiting: C31D1 (n=7, 0)     14.3  ± 17.8     NA  ± NA [2]
Nausea and Vomiting: C32D1 (n=6, 0)     11.1  ± 17.2     NA  ± NA [2]
Nausea and Vomiting: C33D1 (n=6, 0)     11.1  ± 17.2     NA  ± NA [2]
Nausea and Vomiting: C34D1 (n=5, 0)     13.3  ± 18.3     NA  ± NA [2]
Nausea and Vomiting: C35D1 (n=4, 0)     12.5  ± 16.0     NA  ± NA [2]
Nausea and Vomiting: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
Nausea and Vomiting: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Pain: C31D1 (n=7, 0)     4.8  ± 8.1     NA  ± NA [2]
Pain: C32D1 (n=6, 0)     5.6  ± 8.6     NA  ± NA [2]
Pain: C33D1 (n=6, 0)     2.8  ± 6.8     NA  ± NA [2]
Pain: C34D1 (n=5, 0)     3.3  ± 7.5     NA  ± NA [2]
Pain: C35D1 (n=4, 0)     8.3  ± 16.7     NA  ± NA [2]
Pain: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
Pain: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Dyspnea: C31D1 (n=7, 0)     9.5  ± 16.3     NA  ± NA [2]
Dyspnea: C32D1 (n=6, 0)     16.7  ± 18.3     NA  ± NA [2]
Dyspnea: C33D1 (n=6, 0)     11.1  ± 17.2     NA  ± NA [2]
Dyspnea: C34D1 (n=5, 0)     13.3  ± 18.3     NA  ± NA [2]
Dyspnea: C35D1 (n=4, 0)     16.7  ± 19.2     NA  ± NA [2]
Dyspnea: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
Dyspnea: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Insomnia : C31D1 (n=7, 0)     0.0  ± 0.0     NA  ± NA [2]
Insomnia : C32D1 (n=6, 0)     5.6  ± 13.6     NA  ± NA [2]
Insomnia : C33D1 (n=6, 0)     5.6  ± 13.6     NA  ± NA [2]
Insomnia : C34D1 (n=5, 0)     13.3  ± 18.3     NA  ± NA [2]
Insomnia : C35D1 (n=4, 0)     16.7  ± 19.2     NA  ± NA [2]
Insomnia : C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
Insomnia : C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Appetite loss : C31/D1(n=7, 0)     14.3  ± 17.8     NA  ± NA [2]
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  ± NA [1]
Constipation: C31D1 (n=7, 0)     33.3  ± 27.2     NA  ± NA [2]
Constipation: C32D1 (n=6, 0)     33.3  ± 42.2     NA  ± NA [2]
Constipation: C33D1 (n=6, 0)     38.9  ± 25.1     NA  ± NA [2]
Constipation: C34D1 (n=5, 0)     40.0  ± 43.5     NA  ± NA [2]
Constipation: C35D1 (n=4, 0)     33.3  ± 27.2     NA  ± NA [2]
Constipation: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
Constipation: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Diarrhea: C31D1 (n=7, 0)     14.3  ± 17.8     NA  ± NA [2]
Diarrhea: C32D1 (n=6, 0)     11.1  ± 17.2     NA  ± NA [2]
Diarrhea: C33D1 (n=6, 0)     11.1  ± 17.2     NA  ± NA [2]
Diarrhea: C34D1 (n=5, 0)     6.7  ± 14.9     NA  ± NA [2]
Diarrhea: C35D1 (n=4, 0)     16.7  ± 19.2     NA  ± NA [2]
Diarrhea: C36D1 (n=1, 0)     33.3  ± NA [1]   NA  ± NA [2]
Diarrhea: C37D1 (n=1, 0)     33.3  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Financial Difficulties: C31D1 (n=7, 0)     9.5  ± 16.3     NA  ± NA [2]
Financial Difficulties: C32D1 (n=6, 0)     22.2  ± 27.2     NA  ± NA [2]
Financial Difficulties: C33D1 (n=6, 0)     16.7  ± 27.9     NA  ± NA [2]
Financial Difficulties: C34D1 (n=5, 0)     13.3  ± 18.3     NA  ± NA [2]
Financial Difficulties: C35D1 (n=4, 0)     8.3  ± 16.7     NA  ± NA [2]
Financial Difficulties: C36D1 (n=1, 0)     33.3  ± NA [1]   NA  ± NA [2]
Financial Difficulties: C37D1 (n=1, 0)     66.7  ± NA [1]   NA  ± NA [2]
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  ± NA [2]
Appetite loss: C33D1 (n=6, 0)     11.1  ± 17.2     NA  ± NA [2]
Appetite loss: C34D1 (n=5, 0)     13.3  ± 18.3     NA  ± NA [2]
Appetite loss: C35D1 (n=4, 0)     16.7  ± 19.2     NA  ± NA [2]
Appetite loss: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
Appetite loss: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [2]
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.

No statistical analysis provided for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)



14.  Secondary:   European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)   [ Time Frame: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks) ]

Measure Type Secondary
Measure Title European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  164     162  
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)  
[units: units on a scale]
Mean ± Standard Deviation
   
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  ± NA [1]
Dyspnea: C31D1 (n=7, 0)     15.9  ± 8.7     NA  ± NA [2]
Dyspnea: C32D1 (n=6, 0)     18.5  ± 9.1     NA  ± NA [2]
Dyspnea: C33D1 (n=6, 0)     18.5  ± 9.1     NA  ± NA [2]
Dyspnea: C34D1 (n=5, 0)     20.0  ± 5.0     NA  ± NA [2]
Dyspnea: C35D1 (n=4, 0)     16.7  ± 6.4     NA  ± NA [2]
Dyspnea: C36D1 (n=1, 0)     22.2  ± NA [1]   NA  ± NA [2]
Dyspnea: C37D1 (n=1, 0)     11.1  ± NA [1]   NA  ± NA [2]
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  ± NA [1]
Coughing: C31D1 (n=7, 0)     19.0  ± 17.8     NA  ± NA [3]
Coughing: C32D1 (n=6, 0)     16.7  ± 27.9     NA  ± NA [3]
Coughing: C33D1 (n=6, 0)     11.1  ± 17.2     NA  ± NA [3]
Coughing: C34D1 (n=5, 0)     20.0  ± 29.8     NA  ± NA [3]
Coughing: C35D1 (n=4, 0)     33.3  ± 47.1     NA  ± NA [3]
Coughing: C36D1 (n=1, 0)     33.3  ± NA [1]   NA  ± NA [3]
Coughing: C37D1 (n=1, 0)     33.3  ± NA [1]   NA  ± NA [1]
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  ± NA [1]
Hemoptysis: C31D1 (n=7, 0)     0.0  ± 0.0     NA  ± NA [3]
Hemoptysis: C32D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Hemoptysis: C33D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Hemoptysis: C34D1 (n=5, 0)     0.0  ± 0.0     NA  ± NA [3]
Hemoptysis: C35D1 (n=4, 0)     0.0  ± 0.0     NA  ± NA [3]
Hemoptysis: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
Hemoptysis: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
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  ± NA [1]
Sore Mouth: C31D1 (n=7, 0)     9.5  ± 25.2     NA  ± NA [3]
Sore Mouth: C32D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Sore Mouth: C33D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Sore Mouth: C34D1 (n=5, 0)     0.0  ± 0.0     NA  ± NA [3]
Sore Mouth: C35D1 (n=4, 0)     0.0  ± 0.0     NA  ± NA [3]
Sore Mouth: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
Sore Mouth: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
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  ± NA [1]
Dysphagia: C31D1 (n=7, 0)     4.8  ± 12.6     NA  ± NA [3]
Dysphagia: C32D1 (n=6, 0)     5.6  ± 13.6     NA  ± NA [3]
Dysphagia: C33D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Dysphagia: C34D1 (n=5, 0)     6.7  ± 14.9     NA  ± NA [3]
Dysphagia: C35D1 (n=4, 0)     8.3  ± 16.7     NA  ± NA [3]
Dysphagia: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
Dysphagia: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
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  ± NA [1]
Peripheral Neuropathy: C31D1 (n=7, 0)     19.0  ± 32.5     NA  ± NA [3]
Peripheral Neuropathy: C32D1 (n=6, 0)     11.1  ± 27.2     NA  ± NA [3]
Peripheral Neuropathy: C33D1 (n=6, 0)     11.1  ± 27.2     NA  ± NA [3]
Peripheral Neuropathy: C34D1 (n=5, 0)     20.0  ± 44.7     NA  ± NA [3]
Peripheral Neuropathy: C35D1 (n=4, 0)     25.0  ± 50.0     NA  ± NA [3]
Peripheral Neuropathy: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
Peripheral Neuropathy: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
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  ± NA [1]
Alopecia: C31D1 (n=7, 0)     9.5  ± 25.2     NA  ± NA [3]
Alopecia: C32D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Alopecia: C33D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Alopecia: C34D1 (n=5, 0)     0.0  ± 0.0     NA  ± NA [3]
Alopecia: C35D1 (n=4, 0)     0.0  ± 0.0     NA  ± NA [3]
Alopecia: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
Alopecia: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
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  ± NA [1]
Pain in Chest: C31D1 (n=7, 0)     9.5  ± 16.3     NA  ± NA [3]
Pain in Chest: C32D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Pain in Chest: C33D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Pain in Chest: C34D1 (n=5, 0)     6.7  ± 14.9     NA  ± NA [3]
Pain in Chest: C35D1 (n=4, 0)     8.3  ± 16.7     NA  ± NA [3]
Pain in Chest: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
Pain in Chest: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
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  ± NA [1]
Pain in Arm or Shoulder: C31D1 (n=7, 0)     0.0  ± 0.0     NA  ± NA [3]
Pain in Arm or Shoulder: C32D1 (n=6, 0)     11.1  ± 17.2     NA  ± NA [3]
Pain in Arm or Shoulder: C33D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Pain in Arm or Shoulder: C34D1 (n=5, 0)     0.0  ± 0.0     NA  ± NA [3]
Pain in Arm or Shoulder: C35D1 (n=4, 0)     0.0  ± 0.0     NA  ± NA [3]
Pain in Arm or Shoulder: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
Pain in Arm or Shoulder: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
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  ± NA [1]
Pain in Other Parts: C31D1 (n=7, 0)     9.5  ± 16.3     NA  ± NA [3]
Pain in Other Parts: C32D1 (n=6, 0)     5.6  ± 13.6     NA  ± NA [3]
Pain in Other Parts: C33D1 (n=6, 0)     0.0  ± 0.0     NA  ± NA [3]
Pain in Other Parts: C34D1 (n=5, 0)     6.7  ± 14.9     NA  ± NA [3]
Pain in Other Parts: C35D1 (n=4, 0)     0.0  ± 0.0     NA  ± NA [3]
Pain in Other Parts: C36D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
Pain in Other Parts: C37D1 (n=1, 0)     0.0  ± NA [1]   NA  ± NA [3]
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.

No statistical analysis provided for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)



15.  Secondary:   European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)   [ Time Frame: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks) ]

Measure Type Secondary
Measure Title European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)
Measure 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)  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
Crizotinib 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.
Chemotherapy 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.

Measured Values
    Crizotinib     Chemotherapy  
Number of Participants Analyzed  
[units: participants]
  164     161  
European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)  
[units: units on a scale]
Mean ± Standard Deviation
   
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  ± NA [1]
C31D1 (n=7, 0)     68.57  ± 16.76     NA  ± NA [2]
C32D1 (n=6, 0)     65.83  ± 19.41     NA  ± NA [2]
C33D1 (n=6, 0)     67.50  ± 20.34     NA  ± NA [2]
C34D1 (n=5, 0)     68.00  ± 20.80     NA  ± NA [2]
C35D1 (n=4, 0)     72.25  ± 14.84     NA  ± NA [2]
C36D1 (n=1, 0)     90.00  ± NA [1]   NA  ± NA [2]
C37D1 (n=1, 0)     85.00  ± NA [1]   NA  ± NA [2]
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

No statistical analysis provided for European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)



16.  Secondary:   Percentage of Participants With Echinoderm Microtubule Associated Protein-Like 4-Anaplastic Lymphoma Kinase (EML4-ALK) Fusion Variants   [ 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) ]
Results not yet posted.   Anticipated Posting Date:   12/2015   Safety Issue:   No

17.  Secondary:   Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins   [ 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) ]
Results not yet posted.   Anticipated Posting Date:   12/2015   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
These results are from a preliminary clinical study report including final results for PFS and interim results for OS.


  More Information