Trial Outcomes & Findings for 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 (NCT NCT01154140)

Last Updated: 2017-11-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

343 participants

Primary outcome timeframe

Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

Results posted on

2017-11-06

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Crizotinib 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.	Chemotherapy 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.
Overall Study STARTED	172	171
Overall Study Treated	171	169
Overall Study COMPLETED	81	69
Overall Study NOT COMPLETED	91	102

Reasons for withdrawal

Reasons for withdrawal
Measure	Crizotinib 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.	Chemotherapy 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.
Overall Study Death	71	81
Overall Study Lost to Follow-up	4	5
Overall Study Withdrawal by Subject	12	13
Overall Study Other	3	1
Overall Study Randomized but not treated	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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 n=343 Participants Total of all reporting groups
Age, Continuous	50.94 years STANDARD_DEVIATION 11.9 • n=5 Participants	52.89 years STANDARD_DEVIATION 13.1 • n=7 Participants	51.92 years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	104 Participants n=5 Participants	108 Participants n=7 Participants	212 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	63 Participants n=7 Participants	131 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

Population: The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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.
Progression-Free Survival (PFS) Based on IRR	10.9 months Interval 8.3 to 13.9	7.0 months Interval 6.8 to 8.2

SECONDARY outcome

Timeframe: From randomization to death or last date known alive for those not known to have died (up to 72 months)

Population: The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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 Survival (OS)	NA months Interval 45.8 to Median and upper limit of 95% CI were not estimable due to the small number of participants who had event.	47.5 months Interval 32.2 to Upper limit of 95% CI was not estimable due to the small number of participants who had event.

SECONDARY outcome

Timeframe: Month 12, 18

Population: The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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 Survival Probability at Month 12 and 18 Month 12	83.5 percent probability Interval 77.0 to 88.3	78.4 percent probability Interval 71.3 to 83.9
Overall Survival Probability at Month 12 and 18 Month 18	71.5 percent probability Interval 64.0 to 77.7	66.6 percent probability Interval 58.8 to 73.2

SECONDARY outcome

Timeframe: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

Population: The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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.
Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by IRR	74.4 percentage of participants Interval 67.2 to 80.8	45.0 percentage of participants Interval 37.4 to 52.8

SECONDARY outcome

Timeframe: From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=128 Participants 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.	Chemotherapy n=77 Participants 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.
Duration of Response (DR) Based on IRR	49.0 weeks Interval 35.1 to 60.0	22.9 weeks Interval 18.0 to 25.1

SECONDARY outcome

Timeframe: Randomization to first documentation of objective tumor response (up to 35 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=128 Participants 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.	Chemotherapy n=77 Participants 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.
Time to Tumor Response (TTR) Based on IRR	6.1 weeks Interval 2.7 to 41.4	12.1 weeks Interval 5.1 to 36.7

SECONDARY outcome

Timeframe: Week 12

Population: The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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.
Percentage of Participants With Disease Control at Week 12 Based on IRR	78.5 percentage of participants Interval 71.6 to 84.4	68.4 percentage of participants Interval 60.9 to 75.3

SECONDARY outcome

Timeframe: Randomization to objective progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

Population: The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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.
Time to Progression (TTP) Based on IRR	13.6 months Interval 8.5 to 15.0	7.0 months Interval 6.8 to 8.3

SECONDARY outcome

Timeframe: Randomization to objective intracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

Population: The FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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.
Time to Intracranial Progression (IC-TTP) Based on IRR	NA months Median and CI were not reached due to immaturity of data and low number of events.	17.8 months Interval 13.9 to Upper limit of 95% CI was not estimable due to the small number of participants who had event.

SECONDARY outcome

Timeframe: Randomization to objective extracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

Population: FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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.
Time to Extracranial Progression (EC-TTP) Based on IRR	15.2 months Interval 12.6 to 21.9	7.2 months Interval 6.9 to 8.5

SECONDARY outcome

Timeframe: Baseline up to follow up period (up to 72 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=171 Participants 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.	Chemotherapy n=169 Participants 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.
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	99.4 percentage of participants	99.4 percentage of participants
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	41.5 percentage of participants	29.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to follow up period (up to 72 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=171 Participants 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.	Chemotherapy n=169 Participants 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.
Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	98.2 percentage of participants	92.3 percentage of participants
Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	12.9 percentage of participants	8.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to follow up period (up to 72 months)

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=171 Participants 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.	Chemotherapy n=169 Participants 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.
Percentage of Participants With Adverse Events (AEs) According to Maximum Severity Grade 1	7.0 percentage of participants	9.5 percentage of participants
Percentage of Participants With Adverse Events (AEs) According to Maximum Severity Grade 2	28.7 percentage of participants	34.3 percentage of participants
Percentage of Participants With Adverse Events (AEs) According to Maximum Severity Grade 3	41.5 percentage of participants	44.4 percentage of participants
Percentage of Participants With Adverse Events (AEs) According to Maximum Severity Grade 4	8.8 percentage of participants	8.9 percentage of participants
Percentage of Participants With Adverse Events (AEs) According to Maximum Severity Grade 5	13.5 percentage of participants	2.4 percentage of participants

SECONDARY outcome

Timeframe: Predose at Day 1 of Cycle 2, 3 and 5

Population: 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.

Ctrough is the concentration prior to study drug administration on Day 1 of Cycle 2 onwards. PF-06260182 is the metabolite of Crizotinib.

Outcome measures

Outcome measures
Measure	Crizotinib n=162 Participants 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.	Chemotherapy 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.
Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182 Crizotinib Ctrough: Cycle 2 Day 1	324.2 nanogram per milliliter Geometric Coefficient of Variation 39	—
Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182 Crizotinib Ctrough: Cycle 3 Day 1	320.9 nanogram per milliliter Geometric Coefficient of Variation 40	—
Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182 Crizotinib Ctrough: Cycle 5 Day 1	308.2 nanogram per milliliter Geometric Coefficient of Variation 39	—
Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182 PF-06260182 Ctrough: Cycle 2 Day 1	98.4 nanogram per milliliter Geometric Coefficient of Variation 46	—
Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182 PF-06260182 Ctrough: Cycle 3 Day 1	99.0 nanogram per milliliter Geometric Coefficient of Variation 49	—
Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182 PF-06260182 Ctrough: Cycle 5 Day 1	92.9 nanogram per milliliter Geometric Coefficient of Variation 55	—

SECONDARY outcome

Timeframe: 28 days prior to day 1 of study treatment

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=70 Participants 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.	Chemotherapy n=78 Participants 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.
Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants V1	27.1 percentage of participants	25.6 percentage of participants
Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants V2	7.1 percentage of participants	7.7 percentage of participants
Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants V3a	1.4 percentage of participants	1.3 percentage of participants
Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants V3a/b	4.3 percentage of participants	6.4 percentage of participants
Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants No rearrangement	60.0 percentage of participants	59.0 percentage of participants

SECONDARY outcome

Timeframe: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=70 Participants 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.	Chemotherapy n=78 Participants 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.
Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR V1	84.2 percentage of participants Interval 60.4 to 96.6	45.0 percentage of participants Interval 23.1 to 68.5
Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR V2	100 percentage of participants Interval 47.8 to 100.0	33.3 percentage of participants Interval 4.3 to 77.7
Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR V3a	0.0 percentage of participants Upper and lower limit of 95% CI was not estimable as the percentage of participants were 0.0 for this specific strain.	100 percentage of participants Interval 2.5 to 100.0
Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR V3a/b	100 percentage of participants Interval 29.2 to 100.0	60.0 percentage of participants Interval 14.7 to 94.7
Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR No rearrangement	71.4 percentage of participants Interval 55.4 to 84.3	43.5 percentage of participants Interval 28.9 to 58.9

SECONDARY outcome

Timeframe: From randomization of treatment up to deterioration while on study treatment (up to 35 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=166 Participants 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.	Chemotherapy n=163 Participants 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.
Time to Deterioration (TTD) in Chest Pain, Dyspnea or Cough	2.1 months Interval 0.8 to 4.2	0.5 months Interval 0.4 to 0.7

SECONDARY outcome

Timeframe: Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Crizotinib n=166 Participants 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.	Chemotherapy n=163 Participants 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.
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) QLQ-C30 Global QoL	5.9815 units on a scale Interval 3.92 to 8.05	-7.8488 units on a scale Interval -10.15 to -5.55
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) QLQ-C30 Cognitive Functioning	1.1836 units on a scale Interval -0.66 to 3.03	-2.1696 units on a scale Interval -4.21 to -0.13
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) QLQ-C30 Emotional Functioning	8.7431 units on a scale Interval 6.77 to 10.72	1.2266 units on a scale Interval -0.95 to 3.4
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) QLQ-C30 Physical Functioning	5.9370 units on a scale Interval 3.94 to 7.93	-4.4664 units on a scale Interval -6.59 to -2.34
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) QLQ-C30 Role Functioning	4.8122 units on a scale Interval 1.92 to 7.71	-10.7391 units on a scale Interval -13.87 to -7.61
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) QLQ-C30 Social Functioning	4.3790 units on a scale Interval 1.6 to 7.15	-4.3851 units on a scale Interval -7.37 to -1.4

SECONDARY outcome

Timeframe: Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)

Outcome measures

Outcome measures
Measure	Crizotinib n=166 Participants 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.	Chemotherapy n=163 Participants 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.
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) QLQ-C30 Dysponea	-14.9019 units on a scale Interval -17.4 to -12.4	-1.4398 units on a scale Interval -4.21 to 1.33
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) QLQ-C30 Fatigue	-7.3476 units on a scale Interval -9.72 to -4.98	7.6511 units on a scale Interval 5.05 to 10.25
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) QLQ-C30 Financial Difficulties	-0.5984 units on a scale Interval -3.13 to 1.93	0.2203 units on a scale Interval -2.54 to 2.98
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) QLQ-C30 Appetite loss	-5.4906 units on a scale Interval -8.52 to -2.47	8.0070 units on a scale Interval 4.63 to 11.38
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) QLQ-C30 Constipation	6.4858 units on a scale Interval 3.46 to 9.51	10.9194 units on a scale Interval 7.5 to 14.34
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) QLQ-C30 Diarrhea	12.9558 units on a scale Interval 10.67 to 15.24	0.4652 units on a scale Interval -2.2 to 3.13
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) QLQ-C30 Insomnia	-10.3095 units on a scale Interval -13.1 to -7.52	-0.2665 units on a scale Interval -3.38 to 2.84
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) QLQ-C30 Nausea and Vomiting	3.7742 units on a scale Interval 1.54 to 6.01	7.2188 units on a scale Interval 4.66 to 9.78
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) QLQ-C30 Pain	-11.0993 units on a scale Interval -13.27 to -8.92	-1.1716 units on a scale Interval -3.66 to 1.31

SECONDARY outcome

Timeframe: Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=166 Participants 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.	Chemotherapy n=163 Participants 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.
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) QLQ-LC13 Alopecia	-4.4879 units on a scale Interval -6.99 to -1.99	0.3271 units on a scale Interval -2.4 to 3.06
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) QLQ-LC13 Coughing	-16.4819 units on a scale Interval -18.92 to -14.05	-8.0893 units on a scale Interval -10.83 to -5.35
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) QLQ-LC13 Dysphagia	0.7618 units on a scale Interval -0.82 to 2.35	0.09660 units on a scale Interval -1.76 to 1.95
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) QLQ-LC13 Dyspnoea	-9.2029 units on a scale Interval -11.2 to -7.2	-0.1948 units on a scale Interval -2.36 to 1.97
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) QLQ-LC13 Haemoptysis	-3.2197 units on a scale Interval -3.83 to -2.61	-2.3369 units on a scale Interval -3.05 to -1.62
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) QLQ-LC13 Pain in Arm or Shoulder	-10.1693 units on a scale Interval -12.26 to -8.08	-4.1218 units on a scale Interval -6.51 to -1.74
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) QLQ-LC13 Pain in Chest	-8.1437 units on a scale Interval -10.31 to -5.98	-0.04790 units on a scale Interval -2.48 to 2.38
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) QLQ-LC13 Pain in Other Parts	-8.0757 units on a scale Interval -10.28 to -5.87	-1.3040 units on a scale Interval -3.97 to 1.36
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) QLQ-LC13 Peripheral Neuropathy	3.1779 units on a scale Interval 1.04 to 5.31	-0.1742 units on a scale Interval -2.6 to 2.25
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) QLQ-LC13 Sore Mouth	2.2472 units on a scale Interval 0.36 to 4.13	4.3993 units on a scale Interval 2.27 to 6.53

SECONDARY outcome

Timeframe: Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=160 Participants 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.	Chemotherapy n=160 Participants 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.
Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)- Visual Analog Scale (VAS)	4.5323 units on a scale Interval 2.44 to 6.62	0.5415 units on a scale Interval -1.85 to 2.93

SECONDARY outcome

Timeframe: Baseline up to follow up period (up to 72 months)

Population: FA population included all participants who were randomized with study treatment assignment designated according to the initial randomization.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=172 Participants 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.	Chemotherapy n=171 Participants 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.
Percentage of Participants With Hospital Admissions-Healthcare Resource Utilization (HCRU)	40.12 percentage of participants	36.26 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to follow up period (up to 72 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=170 Participants 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.	Chemotherapy n=165 Participants 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.
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 Anemia: Grade 1	47.1 percentage of participants	46.7 percentage of participants
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 Anemia: Grade 2	13.5 percentage of participants	27.9 percentage of participants
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 Anemia: Grade 3	0.6 percentage of participants	10.9 percentage of participants
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 Hemoglobin increased: Grade 1	6.5 percentage of participants	3.0 percentage of participants
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 Hemoglobin increased: Grade 2	0.6 percentage of participants	0.0 percentage of participants
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 Lymphocyte count increased: Grade 2	3.5 percentage of participants	1.2 percentage of participants
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 Lymphopenia: Grade 1	34.1 percentage of participants	26.1 percentage of participants
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 Lymphopenia: Grade 2	24.7 percentage of participants	33.9 percentage of participants
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 Lymphopenia: Grade 3	10.6 percentage of participants	13.9 percentage of participants
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 Lymphopenia: Grade 4	2.4 percentage of participants	1.8 percentage of participants
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 Neutrophils (Absolute): Grade 1	20.6 percentage of participants	14.5 percentage of participants
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 Neutrophils (Absolute): Grade 2	20.0 percentage of participants	26.7 percentage of participants
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 Neutrophils (Absolute): Grade 3	14.1 percentage of participants	13.9 percentage of participants
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 Neutrophils (Absolute): Grade 4	0.6 percentage of participants	3.6 percentage of participants
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 Platelets: Grade 1	9.4 percentage of participants	21.8 percentage of participants
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 Platelets: Grade 2	2.4 percentage of participants	7.9 percentage of participants
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 Platelets: Grade 3	0.6 percentage of participants	7.9 percentage of participants
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 Platelets: Grade 4	0.0 percentage of participants	0.6 percentage of participants
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 White blood cells: Grade 1	23.5 percentage of participants	34.5 percentage of participants
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 White blood cells: Grade 2	22.9 percentage of participants	24.2 percentage of participants
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 White blood cells: Grade 3	2.9 percentage of participants	9.1 percentage of participants
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 White blood cells: Grade 4	0.0 percentage of participants	0.6 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to follow up period (up to 72 months)

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.

Outcome measures

Outcome measures
Measure	Crizotinib n=171 Participants 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.	Chemotherapy n=165 Participants 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.
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 Bilirubin: Grade 3	0.0 percentage of participants	0.6 percentage of participants
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 Creatinine: Grade 1	50.3 percentage of participants	78.8 percentage of participants
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 Creatinine: Grade 2	47.4 percentage of participants	15.8 percentage of participants
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 Creatinine: Grade 3	1.2 percentage of participants	0.0 percentage of participants
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 Hypercalcemia: Grade 1	0.6 percentage of participants	9.1 percentage of participants
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 Hypercalcemia: Grade 4	0.6 percentage of participants	0.0 percentage of participants
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 Hyperglycemia: Grade 1	50.3 percentage of participants	42.4 percentage of participants
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 Hyperglycemia: Grade 2	15.8 percentage of participants	23.6 percentage of participants
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 Hyperglycemia: Grade 3	4.1 percentage of participants	3.6 percentage of participants
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 Hyperkalemia: Grade 1	17.5 percentage of participants	12.1 percentage of participants
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 Hyperkalemia: Grade 2	5.8 percentage of participants	3.0 percentage of participants
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 Hyperkalemia: Grade 3	2.3 percentage of participants	1.8 percentage of participants
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 Hyperkalemia: Grade 4	0.6 percentage of participants	0.0 percentage of participants
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 Hypermagnesemia: Grade 1	17.6 percentage of participants	8.0 percentage of participants
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 Hypermagnesemia: Grade 3	1.8 percentage of participants	0.0 percentage of participants
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 Hypernatremia: Grade 1	21.1 percentage of participants	5.5 percentage of participants
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 Hypernatremia: Grade 2	0.6 percentage of participants	0.0 percentage of participants
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 Hypernatremia: Grade 4	0.6 percentage of participants	0.0 percentage of participants
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 Hypoalbuminemia: Grade 1	35.1 percentage of participants	22.6 percentage of participants
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 Hypoalbuminemia: Grade 2	44.4 percentage of participants	14.6 percentage of participants
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 Hypoalbuminemia: Grade 3	1.2 percentage of participants	0.6 percentage of participants
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 Hypocalcemia: Grade 1	39.8 percentage of participants	24.8 percentage of participants
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 Hypocalcemia: Grade 2	38.0 percentage of participants	4.8 percentage of participants
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 Hypocalcemia: Grade 3	2.3 percentage of participants	0.6 percentage of participants
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 Hypoglycemia: Grade 1	19.9 percentage of participants	3.6 percentage of participants
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 Hypoglycemia: Grade 2	4.7 percentage of participants	1.8 percentage of participants
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 Hypoglycemia: Grade 4	0.0 percentage of participants	0.6 percentage of participants
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 Hypokalemia: Grade 1	14.6 percentage of participants	9.1 percentage of participants
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 Hypokalemia: Grade 3	2.3 percentage of participants	3.0 percentage of participants
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 Hypokalemia: Grade 4	0.0 percentage of participants	0.6 percentage of participants
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 Hypomagnesemia: Grade 1 (n =170, 162)	12.4 percentage of participants	26.5 percentage of participants
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 Hypomagnesemia: Grade 2	0.0 percentage of participants	1.9 percentage of participants
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 Hyponatremia: Grade 1	25.7 percentage of participants	22.4 percentage of participants
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 Hyponatremia: Grade 3	4.1 percentage of participants	5.5 percentage of participants
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 Hyponatremia: Grade 4	0.6 percentage of participants	1.2 percentage of participants
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 Hypophosphatemia: Grade 1	5.3 percentage of participants	3.1 percentage of participants
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 Hypophosphatemia: Grade 2	27.2 percentage of participants	13.0 percentage of participants
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 Hypophosphatemia: Grade 3	13.0 percentage of participants	6.8 percentage of participants
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 Hypophosphatemia: Grade 4	1.2 percentage of participants	0.0 percentage of participants
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 Alanine aminotransferase: Grade 1	64.3 percentage of participants	34.5 percentage of participants
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 Alanine aminotransferase: Grade 2	10.5 percentage of participants	7.3 percentage of participants
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 Alanine aminotransferase: Grade 3	12.3 percentage of participants	1.8 percentage of participants
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 Alanine aminotransferase: Grade 4	2.3 percentage of participants	0.0 percentage of participants
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 Alkaline phosphatase: Grade 1	55.6 percentage of participants	33.9 percentage of participants
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 Alkaline phosphatase: Grade 2	8.8 percentage of participants	4.8 percentage of participants
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 Alkaline phosphatase: Grade 3	0.6 percentage of participants	1.2 percentage of participants
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 Aspartate Aminotransferase: Grade 1	57.9 percentage of participants	32.1 percentage of participants
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 Aspartate Aminotransferase: Grade 2	6.4 percentage of participants	1.8 percentage of participants
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 Aspartate Aminotransferase: Grade 3	7.6 percentage of participants	1.2 percentage of participants
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 Aspartate Aminotransferase: Grade 4	0.6 percentage of participants	0.0 percentage of participants
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 Bilirubin: Grade 1	10.5 percentage of participants	7.3 percentage of participants
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 Bilirubin: Grade 2	5.8 percentage of participants	1.2 percentage of participants

Adverse Events

Crizotinib

Serious events: 71 serious events

Other events: 169 other events

Deaths: 0 deaths

Chemotherapy

Serious events: 49 serious events

Other events: 164 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER