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A Clinical Trial Testing The Efficacy Of Crizotinib Versus Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin In Patients With ALK Positive Non Squamous Cancer Of The Lung (PROFILE 1014)

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ClinicalTrials.gov Identifier: NCT01154140
Recruitment Status : Completed
First Posted : June 30, 2010
Results First Posted : January 5, 2015
Last Update Posted : November 6, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non Squamous Lung Cancer
Intervention Drug: treatment
Enrollment 343
Recruitment Details  
Pre-assignment Details Participants with histologically or cytologically proven diagnosis of locally advanced, recurrent, or metastatic non squamous non small cell lung cancer and tumors with measurable disease were enrolled. Participants were to be positive for translocation or inversion events involving the ALK gene locus as determined by an ALK break apart FISH test.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description Crizotinib 250 mg (milligram) capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of (Response Evaluation Criteria in Solid Tumors) RECIST v1.1 defined PD, as determined by Independent Radiology Review (IRR), at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit. Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 intravenous (IV) infusion according to standard of care was administered over 10 minutes (min); either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an area under the concentration time curve (AUC) of 5 or 6 milligram*minute per millilitre (mg*min/mL), approximately 30 min after end of pemetrexed infusion.
Period Title: Overall Study
Started 172 171
Treated 171 169
Completed 81 69
Not Completed 91 102
Reason Not Completed
Death             71             81
Lost to Follow-up             4             5
Withdrawal by Subject             12             13
Other             3             1
Randomized but not treated             1             2
Arm/Group Title Crizotinib Chemotherapy Total
Hide Arm/Group Description Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit. Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion. Total of all reporting groups
Overall Number of Baseline Participants 172 171 343
Hide Baseline Analysis Population Description
The Full Analysis (FA) population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 172 participants 171 participants 343 participants
50.94  (11.9) 52.89  (13.1) 51.92  (12.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 172 participants 171 participants 343 participants
Female
104
  60.5%
108
  63.2%
212
  61.8%
Male
68
  39.5%
63
  36.8%
131
  38.2%
1.Primary Outcome
Title Progression-Free Survival (PFS) Based on IRR
Hide Description PFS was defined as the time from the date of randomization in study until the date of first documented objective tumor progression (according to RECIST v1.1 as determined by IRR) or death (due to any cause), whichever occurred first. PFS (in months) was calculated as (first event date − randomization date +1)/30.44. Objective progression was defined as a 20 percent (%) increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 millimeter (mm) or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
Time Frame Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Median (95% Confidence Interval)
Unit of Measure: months
10.9
(8.3 to 13.9)
7.0
(6.8 to 8.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was obtained from 1-sided log rank test, stratified by eastern cooperative oncology group performance status (ECOG PS),race,brain metastases. 1-sided log-rank test at 0.0247 level of significance was used to compare PFS between the 2 arms.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.454
Confidence Interval (2-Sided) 95%
0.346 to 0.596
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS (in months) was defined as the duration from start of study treatment to date of death due to any cause. OS = (date of death minus the date of randomization of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored on last date the participants were known to be alive.
Time Frame From randomization to death or last date known alive for those not known to have died (up to 72 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(45.8 to NA)
47.5 [2] 
(32.2 to NA)
[1]
Median and upper limit of 95% CI were not estimable due to the small number of participants who had event.
[2]
Upper limit of 95% CI was not estimable due to the small number of participants who had event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0489
Comments P-value was obtained from 1-sided log rank test, stratified by ECOG PS, race group and brain metastases.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.760
Confidence Interval (2-Sided) 95%
0.548 to 1.053
Estimation Comments HR was calculated based on the Cox Proportional hazards model stratified by ECOG PS, race group, and brain metastases. Assuming proportional hazards, a hazard ratio (less than)<1 indicates a reduction in hazard rate in favor of crizotinib.
3.Secondary Outcome
Title Overall Survival Probability at Month 12 and 18
Hide Description Overall survival probability at Month 12 and 18 was defined as the probability of overall survival at 12 and 18 months respectively, where the OS was defined as the duration from date of randomization to date of death due to any cause. The survival probability was estimated using the Kaplan-Meier method.
Time Frame Month 12, 18
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability
Month 12
83.5
(77.0 to 88.3)
78.4
(71.3 to 83.9)
Month 18
71.5
(64.0 to 77.7)
66.6
(58.8 to 73.2)
4.Secondary Outcome
Title Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by IRR
Hide Description ORR was defined as percentage of participants with complete response (CR) or partial response (PR) according to RECIST v1.1 determined by IRR. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as greater than or equal to (>=) 30% decrease taking as reference the baseline sum of lesion dimensions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No clear progression of non-target disease. No new lesions.
Time Frame Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
74.4
(67.2 to 80.8)
45.0
(37.4 to 52.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments If the PFS endpoint was significant, ORR was to be considered significant if the 2-sided p-value from Pearson chi-square test was (less than or equal to)<= 0.0494.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was obtained from a Pearson chi-square test.
Method Pearson chi-square test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 29.4
Confidence Interval (2-Sided) 95%
19.5 to 39.3
Estimation Comments 95% CI was calculated based on normal distribution.
5.Secondary Outcome
Title Duration of Response (DR) Based on IRR
Hide Description DR: time from first documentation of objective tumor response (CR or PR) to first documentation of PD or death due to any cause, whichever occurred first as per RECIST v1.1 determined by IRR. CR: complete disappearance of all target and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions, disappearance of all non-target lesions. PR: >=30% decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions. c) PD: 20 % increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
Time Frame From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization. Here Overall number of participants analyzed (N) signifies participants with objective tumor response and were evaluable for this outcome measure.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 128 77
Median (95% Confidence Interval)
Unit of Measure: weeks
49.0
(35.1 to 60.0)
22.9
(18.0 to 25.1)
6.Secondary Outcome
Title Time to Tumor Response (TTR) Based on IRR
Hide Description TTR was defined as the time from randomization to first documentation of objective tumor response (CR or PR) according to RECIST v1.1 determined by IRR. CR: complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR: >=30% decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions.
Time Frame Randomization to first documentation of objective tumor response (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization. Here N signifies participants with objective tumor response and were evaluable for this outcome measure.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 128 77
Median (Full Range)
Unit of Measure: weeks
6.1
(2.7 to 41.4)
12.1
(5.1 to 36.7)
7.Secondary Outcome
Title Percentage of Participants With Disease Control at Week 12 Based on IRR
Hide Description Disease control rate at week 12 is defined as the percent of participants with CR, PR, or stable disease (SD) at week 12 according to RECIST v1.1 determined by IRR. The best response of SD would be assigned if SD criteria was met at least once after randomization at a minimum interval of 6 weeks. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR: >=30% decrease taking as reference the baseline sum of lesion dimensions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
78.5
(71.6 to 84.4)
68.4
(60.9 to 75.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments The confidence interval for the difference in percentage was based on normal distribution.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0381
Comments [Not Specified]
Method Pearson chi-square test
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Percentage
Estimated Value 10.067
Confidence Interval (2-Sided) 95%
0.8 to 19.4
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Time to Progression (TTP) Based on IRR
Hide Description TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions. If tumor progression data included more than 1 date, the first date was used. TTP (in months) was calculated as (first event date − randomization date +1)/30.44.
Time Frame Randomization to objective progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Median (95% Confidence Interval)
Unit of Measure: months
13.6
(8.5 to 15.0)
7.0
(6.8 to 8.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments Analysis was based on the Cox Proportional hazards model assuming proportional hazards, a HR <1 indicated a reduction in hazard rate in favor of Crizotinib.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was obtained from 1-sided unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.441
Confidence Interval (2-Sided) 95%
0.335 to 0.582
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time to Intracranial Progression (IC-TTP) Based on IRR
Hide Description IC-TTP was defined similarly to TTP, but only considering intracranial disease (excluding extracranial disease) and the progression was determined based on either new brain metastases or progression of existing brain metastases. TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
Time Frame Randomization to objective intracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
17.8 [2] 
(13.9 to NA)
[1]
Median and CI were not reached due to immaturity of data and low number of events.
[2]
Upper limit of 95% CI was not estimable due to the small number of participants who had event.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments Analysis was based on the Cox Proportional hazards model assuming proportional hazards, a HR less than 1 indicated a reduction in hazard rate in favor of Crizotinib.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0347
Comments P-value was obtained from 1-sided unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.595
Confidence Interval (2-Sided) 95%
0.338 to 1.048
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to Extracranial Progression (EC-TTP) Based on IRR
Hide Description EC-TTP was defined similarly to TTP, but only considering extracranial disease (excluding intracranial disease) and the progression was determined based on either new extracranial lesions or progression of existing extracranial lesions. TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
Time Frame Randomization to objective extracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Median (95% Confidence Interval)
Unit of Measure: months
15.2
(12.6 to 21.9)
7.2
(6.9 to 8.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments Analysis was based on the Cox Proportional hazards model assuming proportional hazards, a HR less than 1 indicated a reduction in hazard rate in favor of Crizotinib.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was obtained from 1-sided unstratified log-rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.387
Confidence Interval (2-Sided) 95%
0.286 to 0.524
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Time Frame Baseline up to follow up period (up to 72 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all randomized participants who received at least 1 dose of study treatment, with treatment assignments designated according to actual study treatment received during the first cycle.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 171 169
Measure Type: Number
Unit of Measure: percentage of participants
AEs 99.4 99.4
SAEs 41.5 29.0
12.Secondary Outcome
Title Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
Time Frame Baseline up to follow up period (up to 72 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all randomized subjects who received at least 1 dose of study treatment, with treatment assignments designated according to actual study treatment received during the first cycle.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 171 169
Measure Type: Number
Unit of Measure: percentage of participants
AEs 98.2 92.3
SAEs 12.9 8.9
13.Secondary Outcome
Title Percentage of Participants With Adverse Events (AEs) According to Maximum Severity
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.
Time Frame Baseline up to follow up period (up to 72 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis population included all randomized subjects who received at least 1 dose of study treatment, with treatment assignments designated according to actual study treatment received during the first cycle.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 171 169
Measure Type: Number
Unit of Measure: percentage of participants
Grade 1 7.0 9.5
Grade 2 28.7 34.3
Grade 3 41.5 44.4
Grade 4 8.8 8.9
Grade 5 13.5 2.4
14.Secondary Outcome
Title Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182
Hide Description Ctrough is the concentration prior to study drug administration on Day 1 of Cycle 2 onwards. PF-06260182 is the metabolite of Crizotinib.
Time Frame Predose at Day 1 of Cycle 2, 3 and 5
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic concentration population included all participants in the safety analysis population who had at least 1 plasma concentration of crizotinib or its metabolite.N=participants evaluable for this measure.Number of participants analyzed(n)=participants evaluable at specified time points.This analysis was performed in crizotinib arm only.
Arm/Group Title Crizotinib
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Overall Number of Participants Analyzed 162
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter
Crizotinib Ctrough: Cycle 2 Day 1 Number Analyzed 91 participants
324.2
(39%)
Crizotinib Ctrough: Cycle 3 Day 1 Number Analyzed 85 participants
320.9
(40%)
Crizotinib Ctrough: Cycle 5 Day 1 Number Analyzed 82 participants
308.2
(39%)
PF-06260182 Ctrough: Cycle 2 Day 1 Number Analyzed 100 participants
98.4
(46%)
PF-06260182 Ctrough: Cycle 3 Day 1 Number Analyzed 94 participants
99.0
(49%)
PF-06260182 Ctrough: Cycle 5 Day 1 Number Analyzed 86 participants
92.9
(55%)
15.Secondary Outcome
Title Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants
Hide Description The Response Genetics, Inc. Echinoderm Microtubule Associated Protein Like 4 (EML4) ALK reverse transcriptase polymerase chain reaction (RT PCR) gene fusion test was used for the analysis of tissue samples for the ALK gene fusion variants (either no rearrangement, or 1 of 9 results reflecting 8 specific rearrangements [V1, V2, V3a, V3b,V3a/b, V4, V5a, V6, V7]). Percentage of participants who tested positive for ALK gene fusion variants were reported in this outcome measure.
Time Frame 28 days prior to day 1 of study treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ALK variant evaluable population included participants from the FA population who had a result from ALK gene fusion variant testing of either no rearrangement, or 1 of 9 results reflecting 8 specific rearrangements (V1, V2, V3a, V3b, V3a/b, V4, V5a, V6, and V7).
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 70 78
Measure Type: Number
Unit of Measure: percentage of participants
V1 27.1 25.6
V2 7.1 7.7
V3a 1.4 1.3
V3a/b 4.3 6.4
No rearrangement 60.0 59.0
16.Secondary Outcome
Title Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR
Hide Description The Response Genetics, Inc. EML4 ALK reverse transcriptase polymerase chain reaction (RT PCR) gene fusion test was used for the analysis of tissue samples for the ALK gene fusion variants (either no rearrangement, or 1 of 9 results reflecting 8 specific rearrangements [V1, V2, V3a, V3b,V3a/b, V4, V5a, V6, V7]). Percentage of participants with confirmed CR or PR according to RECIST v1.1 determined by IRR, by type of ALK gene fusion variant were reported in this outcome measure. CR: complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR: >=30% decrease decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions.
Time Frame Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ALK variant evaluable population included participants from the FA population who had a result from ALK gene fusion variant testing of either no rearrangement, or 1 of 9 results reflecting 8 specific rearrangements (V1, V2, V3a, V3b, V3a/b, V4, V5a, V6, and V7). Here, n signifies participants who were evaluable at specified time points.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 70 78
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
V1 Number Analyzed 19 participants 20 participants
84.2
(60.4 to 96.6)
45.0
(23.1 to 68.5)
V2 Number Analyzed 5 participants 6 participants
100
(47.8 to 100)
33.3
(4.3 to 77.7)
V3a Number Analyzed 1 participants 1 participants
0.0 [1] 
(NA to NA)
100
(2.5 to 100)
V3a/b Number Analyzed 3 participants 5 participants
100
(29.2 to 100)
60.0
(14.7 to 94.7)
No rearrangement Number Analyzed 42 participants 46 participants
71.4
(55.4 to 84.3)
43.5
(28.9 to 58.9)
[1]
Upper and lower limit of 95% CI was not estimable as the percentage of participants were 0.0 for this specific strain.
17.Secondary Outcome
Title Time to Deterioration (TTD) in Chest Pain, Dyspnea or Cough
Hide Description TTD in pain in chest, dyspnea, or cough from the Quality of Life Questionnaire Core 30 (QLQ-LC13) was a composite endpoint defined as the time from randomization to the earliest time the participant’s scale scores showed a 10 point or greater increase after baseline in any of the 3 symptoms. For those who had not shown deterioration, the data was censored at the last date when the participants completed an assessment (QLQ-LC13) for pain, dyspnea, or cough or at last visit date prior to crossover for participants randomized to chemotherapy who subsequently crossed over to crizotinib. A 10-point or higher change in the score was perceived by participants as clinically significant. The transformed score of pain, dyspnea, and cough symptom scales of EORTC QLQ-LC13 (European Organization for the Research and Treatment of Cancer) range from 0 to 100, where higher scores indicate greater symptom severity.
Time Frame From randomization of treatment up to deterioration while on study treatment (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The patient reported outcome (PRO) evaluable population included all participants from the FA population who completed a baseline and at least 1 postbaseline PRO assessment prior to crossover to crizotinib or end of randomized study treatment.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 166 163
Median (95% Confidence Interval)
Unit of Measure: months
2.1
(0.8 to 4.2)
0.5
(0.4 to 0.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments HR was calculated based on the Cox Proportional hazards model. Assuming proportional hazards, a HR less than 1 indicated a reduction in hazard rate in favor of crizotinib.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Two-sided p-value from the unstratified log rank test was used.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.591
Confidence Interval (2-Sided) 95%
0.452 to 0.773
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change From Baseline in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Hide Description EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional and social), global health status/global quality of life scale, 3 symptom scales (fatigue, pain, nausea and vomiting), 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea) and financial difficulties. All scales and single-item measures range from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning, for the global health status/QoL represents a high QoL (better participant state), and for a symptom scale/item represents a high level of symptoms/problems (worse participant state).
Time Frame Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PRO evaluable population included all participants from the FA population who completed a baseline and at least 1 postbaseline PRO assessment prior to crossover to crizotinib or end of randomized study treatment.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 166 163
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
QLQ-C30 Global QoL
5.9815
(3.92 to 8.05)
-7.8488
(-10.15 to -5.55)
QLQ-C30 Cognitive Functioning
1.1836
(-0.66 to 3.03)
-2.1696
(-4.21 to -0.13)
QLQ-C30 Emotional Functioning
8.7431
(6.77 to 10.72)
1.2266
(-0.95 to 3.40)
QLQ-C30 Physical Functioning
5.9370
(3.94 to 7.93)
-4.4664
(-6.59 to -2.34)
QLQ-C30 Role Functioning
4.8122
(1.92 to 7.71)
-10.7391
(-13.87 to -7.61)
QLQ-C30 Social Functioning
4.3790
(1.60 to 7.15)
-4.3851
(-7.37 to -1.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 Global QoL: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 13.8303
Confidence Interval (2-Sided) 95%
10.74 to 16.92
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 cognitive functioning: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0170
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.3532
Confidence Interval (2-Sided) 95%
0.60 to 6.11
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 emotional functioning: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.5165
Confidence Interval (2-Sided) 95%
4.57 to 10.46
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 physical functioning: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 10.4035
Confidence Interval (2-Sided) 95%
7.48 to 13.32
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 role functioning: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 15.5513
Confidence Interval (2-Sided) 95%
11.29 to 19.81
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 social functioning: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.7641
Confidence Interval (2-Sided) 95%
4.69 to 12.84
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline Scores in QLQ-C30 Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Hide Description EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional and social), global health status/global quality of life scale, 3 symptom scales (fatigue, pain, nausea and vomiting), 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea) and financial difficulties. All scales and single-item measures range from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning, for the global health status/QoL represents a high QoL (better participant state), and for a symptom scale/item represents a high level of symptoms/problems (worse participant state).
Time Frame Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PRO evaluable population included all participants from the FA population who completed a baseline and at least 1 postbaseline PRO assessment prior to crossover to crizotinib or end of randomized study treatment.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 166 163
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
QLQ-C30 Appetite loss
-5.4906
(-8.52 to -2.47)
8.0070
(4.63 to 11.38)
QLQ-C30 Constipation
6.4858
(3.46 to 9.51)
10.9194
(7.50 to 14.34)
QLQ-C30 Diarrhea
12.9558
(10.67 to 15.24)
0.4652
(-2.20 to 3.13)
QLQ-C30 Dysponea
-14.9019
(-17.40 to -12.40)
-1.4398
(-4.21 to 1.33)
QLQ-C30 Fatigue
-7.3476
(-9.72 to -4.98)
7.6511
(5.05 to 10.25)
QLQ-C30 Financial Difficulties
-0.5984
(-3.13 to 1.93)
0.2203
(-2.54 to 2.98)
QLQ-C30 Insomnia
-10.3095
(-13.10 to -7.52)
-0.2665
(-3.38 to 2.84)
QLQ-C30 Nausea and Vomiting
3.7742
(1.54 to 6.01)
7.2188
(4.66 to 9.78)
QLQ-C30 Pain
-11.0993
(-13.27 to -8.92)
-1.1716
(-3.66 to 1.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 appetite loss: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -13.4976
Confidence Interval (2-Sided) 95%
-18.03 to -8.97
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 constipation: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0570
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.4336
Confidence Interval (2-Sided) 95%
-9.00 to 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 diarrhea: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 12.4906
Confidence Interval (2-Sided) 95%
8.98 to 16.00
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 dysponea: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -13.4622
Confidence Interval (2-Sided) 95%
-17.20 to -9.73
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 fatigue: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -14.9987
Confidence Interval (2-Sided) 95%
-18.52 to -11.48
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 financial difficulties: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6681
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8186
Confidence Interval (2-Sided) 95%
-4.56 to 2.92
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 insomnia: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -10.0430
Confidence Interval (2-Sided) 95%
-14.22 to -5.87
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 nausea and vomiting: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0468
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.4446
Confidence Interval (2-Sided) 95%
-6.84 to -0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-C30 pain: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -9.9277
Confidence Interval (2-Sided) 95%
-13.23 to -6.62
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in Lung Cancer Symptom Scores as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13)
Hide Description QLQ-LC13 consists of 1 multi-item scale and 9 single items that assess the specific symptoms (dyspnea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of patients with lung cancer receiving chemotherapy. All multi-item scales and single-item measures range from 0 to 100, where higher score indicates greater degree of symptom severity.
Time Frame Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PRO evaluable population included all participants from the FA population who completed a baseline and at least 1 postbaseline PRO assessment prior to crossover to crizotinib or end of randomized study treatment.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 166 163
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
QLQ-LC13 Alopecia
-4.4879
(-6.99 to -1.99)
0.3271
(-2.40 to 3.06)
QLQ-LC13 Coughing
-16.4819
(-18.92 to -14.05)
-8.0893
(-10.83 to -5.35)
QLQ-LC13 Dysphagia
0.7618
(-0.82 to 2.35)
0.09660
(-1.76 to 1.95)
QLQ-LC13 Dyspnoea
-9.2029
(-11.20 to -7.20)
-0.1948
(-2.36 to 1.97)
QLQ-LC13 Haemoptysis
-3.2197
(-3.83 to -2.61)
-2.3369
(-3.05 to -1.62)
QLQ-LC13 Pain in Arm or Shoulder
-10.1693
(-12.26 to -8.08)
-4.1218
(-6.51 to -1.74)
QLQ-LC13 Pain in Chest
-8.1437
(-10.31 to -5.98)
-0.04790
(-2.48 to 2.38)
QLQ-LC13 Pain in Other Parts
-8.0757
(-10.28 to -5.87)
-1.3040
(-3.97 to 1.36)
QLQ-LC13 Peripheral Neuropathy
3.1779
(1.04 to 5.31)
-0.1742
(-2.60 to 2.25)
QLQ-LC13 Sore Mouth
2.2472
(0.36 to 4.13)
4.3993
(2.27 to 6.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 alopecia: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0108
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.8149
Confidence Interval (2-Sided) 95%
-8.52 to -1.11
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 coughing: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -8.3926
Confidence Interval (2-Sided) 95%
-12.06 to -4.72
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 dysphagia: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5938
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.6651
Confidence Interval (2-Sided) 95%
-1.78 to 3.11
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 dyspnoea: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -9.0080
Confidence Interval (2-Sided) 95%
-11.96 to -6.06
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 haemoptysis: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0656
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8828
Confidence Interval (2-Sided) 95%
-1.82 to 0.06
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 pain in arm or shoulder: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.0475
Confidence Interval (2-Sided) 95%
-9.22 to -2.88
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 pain in chest: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -8.0959
Confidence Interval (2-Sided) 95%
-11.35 to -4.84
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 pain in other parts: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.7717
Confidence Interval (2-Sided) 95%
-10.24 to -3.31
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 peripheral neuropathy: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0427
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.3521
Confidence Interval (2-Sided) 95%
0.11 to 6.59
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments QLQ-LC13 sore mouth: Analysis was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1382
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.1521
Confidence Interval (2-Sided) 95%
-5.00 to 0.69
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)- Visual Analog Scale (VAS)
Hide Description EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. VAS component: participants rated their current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health.
Time Frame Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The patient reported outcome (PRO) evaluable population included all participants from the FA population who completed a baseline and at least 1 postbaseline PRO assessment prior to crossover to crizotinib or end of randomized study treatment. Here, "N" signifies participants who were evaluable for this outcome measure.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 160 160
Mean (95% Confidence Interval)
Unit of Measure: units on a scale
4.5323
(2.44 to 6.62)
0.5415
(-1.85 to 2.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib, Chemotherapy
Comments Analysis was based on a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EQ-5D VAS subscale baseline score (intercept and time from first dose were included as random effects).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0139
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.9908
Confidence Interval (2-Sided) 95%
0.81 to 7.17
Estimation Comments [Not Specified]
22.Secondary Outcome
Title Percentage of Participants With Hospital Admissions-Healthcare Resource Utilization (HCRU)
Hide Description Healthcare resource utilization was to be evaluated using the assessment of the following: date and duration of index admission, duration of hospitalization and date of discharge.
Time Frame Baseline up to follow up period (up to 72 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 172 171
Measure Type: Number
Unit of Measure: percentage of participants
40.12 36.26
23.Secondary Outcome
Title Percentage of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities
Hide Description Anemia(grade[g]1:Less than[<] Lower limit of normal[LLN] to 10gram per[/] deciliter[g/dL],g2:<10 to 8g/dL,g3:<8g/dL,g4:lifethreatening);platelet (g1:<LLN to 75*10^3/millimeter[mm]^3,g2:<75*10^3/mm^3 to 50*10^3/mm^3,g3:<50*10^3/mm^3 to 25*10^3/mm^3,g4:<25*10^3/mm^3);lymphopenia(g1:<LLN to 8*10^2/mm^3,g2:<8*10^2 to 5*10^2/mm^3,g3:<5*10^2 to 2*10^2/mm^3,g4:<2*10^2/mm^3);neutrophil (Absolute)(g1:<LLN to 15*10^2/mm^3,g2:<15*10^2 to 10*10^2/mm^3,g3:<10*10^2 to 5*10^2/mm^3,g4:<5*10^2/mm^3);white blood cell count(g1:<LLN to 3*10^3/mm^3,g2:<3*10^3 to 2*10^3/mm^3,g3:<2*10^3 to 1*10^3/mm^3,g4:<1*10^3/mm^3);hemoglobin(g1:increase in hemoglobin level>0 to 2 g/dL above ULN or above baseline if baseline is above ULN,g2:increase in hemoglobin level>2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3:increase in hemoglobin level>4 g/dL above ULN or above baseline if baseline is above ULN). Only categories with atleast 1 participant with abnormality are reported in this outcome measure.
Time Frame Baseline up to follow up period (up to 72 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population included all randomized subjects who received at least 1 dose of study treatment, with treatment assignments designated according to actual study treatment received during the first cycle. Here, N=participants who were evaluable for this outcome measure.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 170 165
Measure Type: Number
Unit of Measure: percentage of participants
Anemia: Grade 1 47.1 46.7
Anemia: Grade 2 13.5 27.9
Anemia: Grade 3 0.6 10.9
Hemoglobin increased: Grade 1 6.5 3.0
Hemoglobin increased: Grade 2 0.6 0.0
Lymphocyte count increased: Grade 2 3.5 1.2
Lymphopenia: Grade 1 34.1 26.1
Lymphopenia: Grade 2 24.7 33.9
Lymphopenia: Grade 3 10.6 13.9
Lymphopenia: Grade 4 2.4 1.8
Neutrophils (Absolute): Grade 1 20.6 14.5
Neutrophils (Absolute): Grade 2 20.0 26.7
Neutrophils (Absolute): Grade 3 14.1 13.9
Neutrophils (Absolute): Grade 4 0.6 3.6
Platelets: Grade 1 9.4 21.8
Platelets: Grade 2 2.4 7.9
Platelets: Grade 3 0.6 7.9
Platelets: Grade 4 0.0 0.6
White blood cells: Grade 1 23.5 34.5
White blood cells: Grade 2 22.9 24.2
White blood cells: Grade 3 2.9 9.1
White blood cells: Grade 4 0.0 0.6
24.Secondary Outcome
Title Percentage of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities
Hide Description ALT/AST (Grade[g]1:>ULN-3*ULN,g2:>3-5*ULN,g3:>5-20*ULN,g4:>20*ULN);Alkaline Phosphatase (g1:>ULN-2.5*ULN,g2:>2.5-5*ULN,g3:>5-20*ULN,g4:>20*ULN);Creatinine (g1:>ULN-1.5*ULN,g2:>1.5-3*ULN,g3:>3-6*ULN,g4:>6*ULN);hyperglycemia (g1:>ULN-160,g2:>160-250,g3:>250-500,g4:>500mg/dL);bilirubin(total) (g1:>ULN-1.5*ULN,g2:>1.5-3*ULN,g3:>3-10*ULN,g4:>10*ULN);hypoglycaemia (g1:<LLN-55,g2:<55-40,g3:<40-30,g4:<30mg/dL);hyperkalemia (g1:>ULN-5.5,g2:>5.5-6,g3:>6-7,g4:>7mmol/L);hypokalemia (g1:<LLN-3,g2:<LLN-3,g3:<3-2.5,g4:<2.5mmol/L);hypermagnesemia (g1:>ULN-3,g3:>3-8,g4:>8mg/dL);hypocalcemia (g1:<LLN-8,g2:<8-7,g3:<7-6,g4:<6mg/dL); hypercalcemia (g1:>ULN-11.5,g2:>11.5-12.5,g3:>12.5-13.5,g4:>13.5mg/dL);hypomagnesemia (g1:<LLN-1.2,g2:<1.2-0.9,g3:<0.9-0.7,g4:<0.7mg/dL);hyponatremia (g1:<LLN-130,g3:<130-120,g4:<120mmol/L);hypoalbuminemia (g1:<LLN-3,g2:<3-2,g3:<2,g4:lifethreatening);hypophosphatemia (g1:<LLN-2.5,g2:<2.5-2,g3:<2-1,g4:<1mg/dL). Participant>=1 abnormality given.
Time Frame Baseline up to follow up period (up to 72 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population included all randomized subjects who received at least 1 dose of study treatment, with treatment assignments designated according to actual study treatment received during the first cycle. Here, N=participants who were evaluable for this outcome measure. Here, "n"=participants who were evaluable at specified time points.
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description:
Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit.
Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
Overall Number of Participants Analyzed 171 165
Measure Type: Number
Unit of Measure: percentage of participants
Alanine aminotransferase: Grade 1 Number Analyzed 171 participants 165 participants
64.3 34.5
Alanine aminotransferase: Grade 2 Number Analyzed 171 participants 165 participants
10.5 7.3
Alanine aminotransferase: Grade 3 Number Analyzed 171 participants 165 participants
12.3 1.8
Alanine aminotransferase: Grade 4 Number Analyzed 171 participants 165 participants
2.3 0.0
Alkaline phosphatase: Grade 1 Number Analyzed 171 participants 165 participants
55.6 33.9
Alkaline phosphatase: Grade 2 Number Analyzed 171 participants 165 participants
8.8 4.8
Alkaline phosphatase: Grade 3 Number Analyzed 171 participants 165 participants
0.6 1.2
Aspartate Aminotransferase: Grade 1 Number Analyzed 171 participants 165 participants
57.9 32.1
Aspartate Aminotransferase: Grade 2 Number Analyzed 171 participants 165 participants
6.4 1.8
Aspartate Aminotransferase: Grade 3 Number Analyzed 171 participants 165 participants
7.6 1.2
Aspartate Aminotransferase: Grade 4 Number Analyzed 171 participants 165 participants
0.6 0.0
Bilirubin: Grade 1 Number Analyzed 171 participants 165 participants
10.5 7.3
Bilirubin: Grade 2 Number Analyzed 171 participants 165 participants
5.8 1.2
Bilirubin: Grade 3 Number Analyzed 171 participants 165 participants
0.0 0.6
Creatinine: Grade 1 Number Analyzed 171 participants 165 participants
50.3 78.8
Creatinine: Grade 2 Number Analyzed 171 participants 165 participants
47.4 15.8
Creatinine: Grade 3 Number Analyzed 171 participants 165 participants
1.2 0.0
Hypercalcemia: Grade 1 Number Analyzed 171 participants 165 participants
0.6 9.1
Hypercalcemia: Grade 4 Number Analyzed 171 participants 165 participants
0.6 0.0
Hyperglycemia: Grade 1 Number Analyzed 171 participants 165 participants
50.3 42.4
Hyperglycemia: Grade 2 Number Analyzed 171 participants 165 participants
15.8 23.6
Hyperglycemia: Grade 3 Number Analyzed 171 participants 165 participants
4.1 3.6
Hyperkalemia: Grade 1 Number Analyzed 171 participants 165 participants
17.5 12.1
Hyperkalemia: Grade 2 Number Analyzed 171 participants 165 participants
5.8 3.0
Hyperkalemia: Grade 3 Number Analyzed 171 participants 165 participants
2.3 1.8
Hyperkalemia: Grade 4 Number Analyzed 171 participants 165 participants
0.6 0.0
Hypermagnesemia: Grade 1 Number Analyzed 171 participants 162 participants
17.6 8.0
Hypermagnesemia: Grade 3 Number Analyzed 171 participants 162 participants
1.8 0.0
Hypernatremia: Grade 1 Number Analyzed 171 participants 165 participants
21.1 5.5
Hypernatremia: Grade 2 Number Analyzed 171 participants 165 participants
0.6 0.0
Hypernatremia: Grade 4 Number Analyzed 171 participants 165 participants
0.6 0.0
Hypoalbuminemia: Grade 1 Number Analyzed 171 participants 164 participants
35.1 22.6
Hypoalbuminemia: Grade 2 Number Analyzed 171 participants 164 participants
44.4 14.6
Hypoalbuminemia: Grade 3 Number Analyzed 171 participants 164 participants
1.2 0.6
Hypocalcemia: Grade 1 Number Analyzed 171 participants 165 participants
39.8 24.8
Hypocalcemia: Grade 2 Number Analyzed 171 participants 165 participants
38.0 4.8
Hypocalcemia: Grade 3 Number Analyzed 171 participants 165 participants
2.3 0.6
Hypoglycemia: Grade 1 Number Analyzed 171 participants 165 participants
19.9 3.6
Hypoglycemia: Grade 2 Number Analyzed 171 participants 165 participants
4.7 1.8
Hypoglycemia: Grade 4 Number Analyzed 171 participants 165 participants
0.0 0.6
Hypokalemia: Grade 1 Number Analyzed 171 participants 165 participants
14.6 9.1
Hypokalemia: Grade 3 Number Analyzed 171 participants 165 participants
2.3 3.0
Hypokalemia: Grade 4 Number Analyzed 171 participants 165 participants
0.0 0.6
Hypomagnesemia: Grade 1 (n =170, 162) Number Analyzed 170 participants 162 participants
12.4 26.5
Hypomagnesemia: Grade 2 Number Analyzed 170 participants 162 participants
0.0 1.9
Hyponatremia: Grade 1 Number Analyzed 171 participants 165 participants
25.7 22.4
Hyponatremia: Grade 3 Number Analyzed 171 participants 165 participants
4.1 5.5
Hyponatremia: Grade 4 Number Analyzed 171 participants 165 participants
0.6 1.2
Hypophosphatemia: Grade 1 Number Analyzed 169 participants 161 participants
5.3 3.1
Hypophosphatemia: Grade 2 Number Analyzed 169 participants 161 participants
27.2 13.0
Hypophosphatemia: Grade 3 Number Analyzed 169 participants 161 participants
13.0 6.8
Hypophosphatemia: Grade 4 Number Analyzed 169 participants 161 participants
1.2 0.0
Time Frame Baseline up to follow up period (up to 72 months)
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Crizotinib Chemotherapy
Hide Arm/Group Description Crizotinib 250 mg capsule, orally twice daily was administered in treatment cycle of 21 days. Participants could continue crizotinib treatment beyond the time of RECIST v1.1 defined PD, as determined by IRR, at the discretion of the investigator if the participant was perceived to be experiencing clinical benefit. Standard doses of chemotherapy (pemetrexed/cisplatin or pemetrexed/carboplatin) were administered intravenously on Day 1 of each cycle for a maximum of 6 cycles. Pemetrexed 500 mg per meter square (m)^2 IV infusion according to standard of care was administered over 10 min; either cisplatin 75 mg/m^2 IV infusion was administered approximately 30 min after the end of the pemetrexed infusion or carboplatin was administered at a dose calculated to produce an AUC of 5 or 6 mg*min/mL, approximately 30 min after end of pemetrexed infusion.
All-Cause Mortality
Crizotinib Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Crizotinib Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   71/171 (41.52%)   49/169 (28.99%) 
Blood and lymphatic system disorders     
Lymphadenopathy mediastinal * 1  1/171 (0.58%)  0/169 (0.00%) 
Anaemia * 1  0/171 (0.00%)  1/169 (0.59%) 
Febrile neutropenia * 1  0/171 (0.00%)  2/169 (1.18%) 
Cardiac disorders     
Atrial fibrillation * 1  1/171 (0.58%)  1/169 (0.59%) 
Atrioventricular block * 1  1/171 (0.58%)  0/169 (0.00%) 
Pericardial effusion * 1  0/171 (0.00%)  1/169 (0.59%) 
Pericarditis * 1  0/171 (0.00%)  1/169 (0.59%) 
Syncope * 1  0/171 (0.00%)  2/169 (1.18%) 
Cardiac arrest * 1  0/171 (0.00%)  1/169 (0.59%) 
Myocardial ischaemia * 1  0/171 (0.00%)  1/169 (0.59%) 
Bradycardia * 1  1/171 (0.58%)  0/169 (0.00%) 
Cardiac tamponade * 1  2/171 (1.17%)  0/169 (0.00%) 
Gastrointestinal disorders     
Abdominal pain * 1  1/171 (0.58%)  0/169 (0.00%) 
Constipation * 1  0/171 (0.00%)  1/169 (0.59%) 
Diarrhoea * 1  2/171 (1.17%)  1/169 (0.59%) 
Dysphagia * 1  0/171 (0.00%)  1/169 (0.59%) 
Haemorrhoids * 1  1/171 (0.58%)  0/169 (0.00%) 
Intestinal obstruction * 1  2/171 (1.17%)  0/169 (0.00%) 
Nausea * 1  4/171 (2.34%)  1/169 (0.59%) 
Oesophageal ulcer * 1  1/171 (0.58%)  0/169 (0.00%) 
Oesophagitis * 1  3/171 (1.75%)  0/169 (0.00%) 
Vomiting * 1  3/171 (1.75%)  4/169 (2.37%) 
Colitis * 1  1/171 (0.58%)  0/169 (0.00%) 
General disorders     
Chest pain * 1  1/171 (0.58%)  1/169 (0.59%) 
Disease progression * 1  18/171 (10.53%)  1/169 (0.59%) 
Fatigue * 1  1/171 (0.58%)  0/169 (0.00%) 
General physical health deterioration * 1  0/171 (0.00%)  2/169 (1.18%) 
Oedema peripheral * 1  1/171 (0.58%)  0/169 (0.00%) 
Pyrexia * 1  1/171 (0.58%)  2/169 (1.18%) 
Asthenia * 1  2/171 (1.17%)  0/169 (0.00%) 
Death * 1  1/171 (0.58%)  0/169 (0.00%) 
Hepatobiliary disorders     
Drug-induced liver injury * 1  1/171 (0.58%)  0/169 (0.00%) 
Cholecystitis * 1  2/171 (1.17%)  0/169 (0.00%) 
Cholecystitis acute * 1  0/171 (0.00%)  1/169 (0.59%) 
Bile duct obstruction * 1  0/171 (0.00%)  1/169 (0.59%) 
Infections and infestations     
Abdominal abscess * 1  1/171 (0.58%)  0/169 (0.00%) 
Cellulitis * 1  2/171 (1.17%)  0/169 (0.00%) 
Hepatitis B * 1  1/171 (0.58%)  0/169 (0.00%) 
Lower respiratory tract infection * 1  2/171 (1.17%)  0/169 (0.00%) 
Periodontitis * 1  1/171 (0.58%)  0/169 (0.00%) 
Pneumonia * 1  3/171 (1.75%)  1/169 (0.59%) 
Pulmonary sepsis * 1  1/171 (0.58%)  0/169 (0.00%) 
Respiratory tract infection * 1  2/171 (1.17%)  1/169 (0.59%) 
Septic shock * 1  2/171 (1.17%)  0/169 (0.00%) 
Upper respiratory tract infection * 1  1/171 (0.58%)  0/169 (0.00%) 
Urinary tract infection * 1  2/171 (1.17%)  0/169 (0.00%) 
Bronchitis * 1  0/171 (0.00%)  1/169 (0.59%) 
Lung infection * 1  1/171 (0.58%)  0/169 (0.00%) 
Sepsis * 1  2/171 (1.17%)  0/169 (0.00%) 
Arthritis bacterial * 1  1/171 (0.58%)  0/169 (0.00%) 
Influenza * 1  1/171 (0.58%)  0/169 (0.00%) 
Neutropenic sepsis * 1  1/171 (0.58%)  0/169 (0.00%) 
Peritonitis * 1  1/171 (0.58%)  0/169 (0.00%) 
Pyelonephritis * 1  1/171 (0.58%)  0/169 (0.00%) 
Respiratory tract infection viral * 1  1/171 (0.58%)  0/169 (0.00%) 
Skin infection * 1  1/171 (0.58%)  0/169 (0.00%) 
Atypical pneumonia * 1  1/171 (0.58%)  0/169 (0.00%) 
Injury, poisoning and procedural complications     
Overdose * 1  0/171 (0.00%)  1/169 (0.59%) 
Rib fracture * 1  0/171 (0.00%)  1/169 (0.59%) 
Investigations     
Alanine aminotransferase increased * 1  1/171 (0.58%)  0/169 (0.00%) 
Aspartate aminotransferase increased * 1  1/171 (0.58%)  0/169 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  2/171 (1.17%)  0/169 (0.00%) 
Dehydration * 1  0/171 (0.00%)  2/169 (1.18%) 
Diabetic ketoacidosis * 1  1/171 (0.58%)  0/169 (0.00%) 
Hypokalaemia * 1  1/171 (0.58%)  0/169 (0.00%) 
Hyponatraemia * 1  1/171 (0.58%)  1/169 (0.59%) 
Hypoproteinaemia * 1  1/171 (0.58%)  0/169 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthritis * 1  2/171 (1.17%)  0/169 (0.00%) 
Bone pain * 1  1/171 (0.58%)  0/169 (0.00%) 
Muscle spasms * 1  0/171 (0.00%)  1/169 (0.59%) 
Muscular weakness * 1  2/171 (1.17%)  0/169 (0.00%) 
Osteonecrosis * 1  1/171 (0.58%)  0/169 (0.00%) 
Rotator cuff syndrome * 1  0/171 (0.00%)  1/169 (0.59%) 
Spinal column stenosis * 1  1/171 (0.58%)  0/169 (0.00%) 
Flank pain * 1  1/171 (0.58%)  0/169 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Thyroid adenoma * 1  0/171 (0.00%)  1/169 (0.59%) 
Nervous system disorders     
Altered state of consciousness * 1  1/171 (0.58%)  0/169 (0.00%) 
Central nervous system lesion * 1  1/171 (0.58%)  0/169 (0.00%) 
Headache * 1  3/171 (1.75%)  0/169 (0.00%) 
Loss of consciousness * 1  1/171 (0.58%)  0/169 (0.00%) 
Multiple sclerosis * 1  1/171 (0.58%)  0/169 (0.00%) 
Partial seizures * 1  0/171 (0.00%)  1/169 (0.59%) 
Transient ischaemic attack * 1  0/171 (0.00%)  1/169 (0.59%) 
Cervicobrachial syndrome * 1  1/171 (0.58%)  0/169 (0.00%) 
Dizziness * 1  1/171 (0.58%)  0/169 (0.00%) 
Paraesthesia * 1  1/171 (0.58%)  0/169 (0.00%) 
Seizure * 1  1/171 (0.58%)  5/169 (2.96%) 
Pregnancy, puerperium and perinatal conditions     
Unintended pregnancy * 1 [1]  1/104 (0.96%)  0/108 (0.00%) 
Psychiatric disorders     
Completed suicide * 1  0/171 (0.00%)  1/169 (0.59%) 
Hypomania * 1  1/171 (0.58%)  0/169 (0.00%) 
Renal and urinary disorders     
Haematuria * 1  0/171 (0.00%)  1/169 (0.59%) 
Renal cyst * 1  3/171 (1.75%)  0/169 (0.00%) 
Urinary retention * 1  1/171 (0.58%)  0/169 (0.00%) 
Dysuria * 1  1/171 (0.58%)  0/169 (0.00%) 
Acute kidney injury * 1  0/171 (0.00%)  1/169 (0.59%) 
Reproductive system and breast disorders     
Uterine prolapse * 1 [1]  1/104 (0.96%)  0/108 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure * 1  1/171 (0.58%)  0/169 (0.00%) 
Asthma * 1  0/171 (0.00%)  1/169 (0.59%) 
Dyspnoea * 1  7/171 (4.09%)  4/169 (2.37%) 
Haemoptysis * 1  0/171 (0.00%)  2/169 (1.18%) 
Pneumothorax * 1  0/171 (0.00%)  1/169 (0.59%) 
Interstitial lung disease * 1  1/171 (0.58%)  1/169 (0.59%) 
Lung infiltration * 1  0/171 (0.00%)  1/169 (0.59%) 
Pleural effusion * 1  2/171 (1.17%)  5/169 (2.96%) 
Pleurisy * 1  0/171 (0.00%)  1/169 (0.59%) 
Pneumonitis * 1  1/171 (0.58%)  0/169 (0.00%) 
Pulmonary embolism * 1  5/171 (2.92%)  7/169 (4.14%) 
Pulmonary oedema * 1  0/171 (0.00%)  1/169 (0.59%) 
Acute respiratory distress syndrome * 1  1/171 (0.58%)  0/169 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  1/171 (0.58%)  1/169 (0.59%) 
Orthostatic hypotension * 1  1/171 (0.58%)  0/169 (0.00%) 
Aortic dissection * 1  1/171 (0.58%)  0/169 (0.00%) 
Embolism * 1  1/171 (0.58%)  0/169 (0.00%) 
Phlebitis * 1  1/171 (0.58%)  0/169 (0.00%) 
Superior vena cava syndrome * 1  1/171 (0.58%)  0/169 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 19.1
[1]
This adverse event is gender specific.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Crizotinib Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   169/171 (98.83%)   164/169 (97.04%) 
Blood and lymphatic system disorders     
Anaemia * 1  18/171 (10.53%)  53/169 (31.36%) 
Leukopenia * 1  8/171 (4.68%)  16/169 (9.47%) 
Thrombocytopenia * 1  1/171 (0.58%)  14/169 (8.28%) 
Neutropenia * 1  32/171 (18.71%)  36/169 (21.30%) 
Cardiac disorders     
Bradycardia * 1  22/171 (12.87%)  0/169 (0.00%) 
Sinus bradycardia * 1  10/171 (5.85%)  1/169 (0.59%) 
Ear and labyrinth disorders     
Tinnitus * 1  4/171 (2.34%)  10/169 (5.92%) 
Eye disorders     
Photopsia * 1  18/171 (10.53%)  2/169 (1.18%) 
Vision blurred * 1  13/171 (7.60%)  5/169 (2.96%) 
Visual impairment * 1  98/171 (57.31%)  5/169 (2.96%) 
Vitreous floaters * 1  11/171 (6.43%)  1/169 (0.59%) 
Gastrointestinal disorders     
Abdominal pain * 1  25/171 (14.62%)  8/169 (4.73%) 
Abdominal pain upper * 1  27/171 (15.79%)  10/169 (5.92%) 
Constipation * 1  78/171 (45.61%)  51/169 (30.18%) 
Diarrhoea * 1  111/171 (64.91%)  22/169 (13.02%) 
Dyspepsia * 1  27/171 (15.79%)  5/169 (2.96%) 
Dysphagia * 1  19/171 (11.11%)  3/169 (1.78%) 
Gastrooesophageal reflux disease * 1  14/171 (8.19%)  6/169 (3.55%) 
Nausea * 1  100/171 (58.48%)  98/169 (57.99%) 
Stomatitis * 1  13/171 (7.60%)  17/169 (10.06%) 
Vomiting * 1  87/171 (50.88%)  57/169 (33.73%) 
Abdominal distension * 1  11/171 (6.43%)  1/169 (0.59%) 
General disorders     
Asthenia * 1  28/171 (16.37%)  40/169 (23.67%) 
Chest pain * 1  21/171 (12.28%)  14/169 (8.28%) 
Fatigue * 1  54/171 (31.58%)  66/169 (39.05%) 
Mucosal inflammation * 1  2/171 (1.17%)  9/169 (5.33%) 
Oedema peripheral * 1  89/171 (52.05%)  12/169 (7.10%) 
Pyrexia * 1  40/171 (23.39%)  17/169 (10.06%) 
Influenza like illness * 1  10/171 (5.85%)  1/169 (0.59%) 
Pain * 1  9/171 (5.26%)  5/169 (2.96%) 
Infections and infestations     
Nasopharyngitis * 1  30/171 (17.54%)  5/169 (2.96%) 
Upper respiratory tract infection * 1  41/171 (23.98%)  13/169 (7.69%) 
Bronchitis * 1  11/171 (6.43%)  2/169 (1.18%) 
Conjunctivitis * 1  3/171 (1.75%)  10/169 (5.92%) 
Rhinitis * 1  9/171 (5.26%)  2/169 (1.18%) 
Urinary tract infection * 1  10/171 (5.85%)  2/169 (1.18%) 
Investigations     
Alanine aminotransferase increased * 1  59/171 (34.50%)  21/169 (12.43%) 
Aspartate aminotransferase increased * 1  47/171 (27.49%)  16/169 (9.47%) 
Electrocardiogram QT prolonged * 1  11/171 (6.43%)  2/169 (1.18%) 
Neutrophil count decreased * 1  14/171 (8.19%)  17/169 (10.06%) 
Platelet count decreased * 1  1/171 (0.58%)  19/169 (11.24%) 
Weight decreased * 1  12/171 (7.02%)  5/169 (2.96%) 
Weight increased * 1  16/171 (9.36%)  4/169 (2.37%) 
White blood cell count decreased * 1  11/171 (6.43%)  12/169 (7.10%) 
Blood bilirubin increased * 1  9/171 (5.26%)  2/169 (1.18%) 
Blood creatinine increased * 1  9/171 (5.26%)  5/169 (2.96%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  59/171 (34.50%)  58/169 (34.32%) 
Hypoalbuminaemia * 1  19/171 (11.11%)  2/169 (1.18%) 
Hypomagnesaemia * 1  3/171 (1.75%)  13/169 (7.69%) 
Hypocalcaemia * 1  10/171 (5.85%)  1/169 (0.59%) 
Hypophosphataemia * 1  10/171 (5.85%)  2/169 (1.18%) 
Hypoproteinaemia * 1  10/171 (5.85%)  0/169 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  25/171 (14.62%)  11/169 (6.51%) 
Back pain * 1  35/171 (20.47%)  20/169 (11.83%) 
Bone pain * 1  12/171 (7.02%)  4/169 (2.37%) 
Muscle spasms * 1  17/171 (9.94%)  2/169 (1.18%) 
Musculoskeletal pain * 1  21/171 (12.28%)  8/169 (4.73%) 
Pain in extremity * 1  44/171 (25.73%)  14/169 (8.28%) 
Flank pain * 1  9/171 (5.26%)  2/169 (1.18%) 
Muscular weakness * 1  9/171 (5.26%)  4/169 (2.37%) 
Musculoskeletal chest pain * 1  10/171 (5.85%)  5/169 (2.96%) 
Myalgia * 1  14/171 (8.19%)  6/169 (3.55%) 
Neck pain * 1  11/171 (6.43%)  2/169 (1.18%) 
Nervous system disorders     
Dizziness * 1  35/171 (20.47%)  15/169 (8.88%) 
Dysgeusia * 1  45/171 (26.32%)  9/169 (5.33%) 
Headache * 1  48/171 (28.07%)  25/169 (14.79%) 
Neuropathy peripheral * 1  4/171 (2.34%)  12/169 (7.10%) 
Paraesthesia * 1  29/171 (16.96%)  8/169 (4.73%) 
Peripheral sensory neuropathy * 1  6/171 (3.51%)  10/169 (5.92%) 
Psychiatric disorders     
Anxiety * 1  10/171 (5.85%)  9/169 (5.33%) 
Insomnia * 1  23/171 (13.45%)  15/169 (8.88%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  44/171 (25.73%)  28/169 (16.57%) 
Dyspnoea * 1  31/171 (18.13%)  23/169 (13.61%) 
Haemoptysis * 1  11/171 (6.43%)  6/169 (3.55%) 
Oropharyngeal pain * 1  14/171 (8.19%)  8/169 (4.73%) 
Productive cough * 1  15/171 (8.77%)  8/169 (4.73%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  16/171 (9.36%)  17/169 (10.06%) 
Pruritus * 1  9/171 (5.26%)  10/169 (5.92%) 
Rash * 1  22/171 (12.87%)  20/169 (11.83%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 19.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01154140     History of Changes
Other Study ID Numbers: A8081014
2010-021336-33 ( EudraCT Number )
XALCORI ( Other Identifier: Alias Study Number )
First Submitted: June 29, 2010
First Posted: June 30, 2010
Results First Submitted: November 26, 2014
Results First Posted: January 5, 2015
Last Update Posted: November 6, 2017