Trial Outcomes & Findings for A Study of Tarceva (Erlotinib) or Placebo in Combination With Platinum-Based Therapy as First Line Treatment in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer (NCT NCT00883779)

Last Updated: 2015-12-14

Results Overview

Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. PFS is the time (in months) between the date of randomization and the date of first documented disease progression or death from any cause, whichever comes first. Participants who had neither progressed nor died at the time of data cut-off or who were lost to follow-up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow up for progression of disease, whichever was last. Participants without post baseline tumor assessments who were known to be alive were censored at the time of randomization. Analysis was performed using Kaplan-Meier method.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

451 participants

Primary outcome timeframe

Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Results posted on

2015-12-14

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Participants received 1250 milligrams per squared meter (mg/m\^2) of gemcitabine intravenous (IV) infusion on Day 1 and 8, carboplatin 5 times (5x) area under concentration versus time curve (AUC) or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day Cycle) until disease progression (PD), unacceptable toxicity or death in primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 milligrams per day (mg/day) from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Primary Study Treatment Phase STARTED	225	226
Primary Study Treatment Phase COMPLETED	120	140
Primary Study Treatment Phase NOT COMPLETED	105	86
Post-Study Treatment Phase STARTED	112	135
Post-Study Treatment Phase COMPLETED	0	0
Post-Study Treatment Phase NOT COMPLETED	112	135
Off-study Phase STARTED	209	202
Off-study Phase COMPLETED	0	0
Off-study Phase NOT COMPLETED	209	202

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received 1250 milligrams per squared meter (mg/m\^2) of gemcitabine intravenous (IV) infusion on Day 1 and 8, carboplatin 5 times (5x) area under concentration versus time curve (AUC) or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day Cycle) until disease progression (PD), unacceptable toxicity or death in primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 milligrams per day (mg/day) from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Primary Study Treatment Phase Did not receive allocated intervention	4	4
Primary Study Treatment Phase Disease progression	75	59
Primary Study Treatment Phase Adverse Event	16	16
Primary Study Treatment Phase Death	2	3
Primary Study Treatment Phase Refused Treatment	5	4
Primary Study Treatment Phase Other	3	0
Post-Study Treatment Phase Adverse Event	2	3
Post-Study Treatment Phase Death	1	3
Post-Study Treatment Phase Protocol Violation	0	1
Post-Study Treatment Phase Refused Treatment	3	0
Post-Study Treatment Phase Disease progression	103	122
Post-Study Treatment Phase Other	3	0
Post-Study Treatment Phase Ongoing in the study	0	6
Off-study Phase Death	185	174
Off-study Phase Refused treatment	1	1
Off-study Phase Failure to return	5	6
Off-study Phase Other	18	21

Baseline Characteristics

A Study of Tarceva (Erlotinib) or Placebo in Combination With Platinum-Based Therapy as First Line Treatment in Patients With Advanced or Recurrent Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).	Total n=451 Participants Total of all reporting groups
Age, Continuous	56.4 years STANDARD_DEVIATION 11.08 • n=5 Participants	57.2 years STANDARD_DEVIATION 9.71 • n=7 Participants	56.8 years STANDARD_DEVIATION 10.41 • n=5 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	94 Participants n=7 Participants	179 Participants n=5 Participants
Sex: Female, Male Male	140 Participants n=5 Participants	132 Participants n=7 Participants	272 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Population: FAS population.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Median Progression Free Survival (PFS) Time	6.0 months Interval 6.0 to 7.0	7.6 months Interval 7.0 to 8.0

SECONDARY outcome

Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Population: FAS population.

Tumor response was evaluated according to RECIST (version 1.0). PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Percentage of Participants Alive and Free From Disease Progression	6.2 percentage of participants	22.6 percentage of participants

SECONDARY outcome

Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Population: FAS population. "n" is the number of participants evaluable under the specified category.

Tumor response was evaluated according to RECIST (version 1.0). PD was defined in outcome measure 1. PFS is the time (in months) between the date of randomization and the date of first documented disease progression or death from any cause, whichever comes first. Participants who had neither progressed nor died at the time of data cut-off or who were lost to follow-up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow up for progression of disease, whichever was last. Participants without post baseline tumor assessments who were known to be alive were censored at the time of randomization. PFS among different subgroups of type of carcinoma, smoking habit, epidermal growth factor receptor (EGFR) mutation type, KRAS mutation type, EGFR immunohistochemistry (IHC) test result type, and EGFR fluorescent in situ hybridization (FISH) result type.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Median PFS Time Based on Different Subgroups EGFR IHC negative (n=25,12)	6.7 months Interval 4.6 to 7.6	10.1 months Interval 7.6 to 15.6
Median PFS Time Based on Different Subgroups Adenocarcinoma (n=168,174)	6.5 months Interval 6.0 to 7.0	8.2 months Interval 8.0 to 11.0
Median PFS Time Based on Different Subgroups Non-adenocarcinoma (n=57,52)	5.8 months Interval 5.0 to 7.0	5.7 months Interval 3.0 to 7.0
Median PFS Time Based on Different Subgroups Never smoked (n=107,112)	6.6 months Interval 5.0 to 7.0	10.9 months Interval 9.0 to 14.0
Median PFS Time Based on Different Subgroups Former/current smoker (n=118,114)	5.9 months Interval 5.5 to 7.1	5.7 months Interval 4.0 to 7.0
Median PFS Time Based on Different Subgroups EGFR mutation (n=48,49)	6.9 months Interval 5.0 to 8.0	15.6 months Interval 13.0 to Estimate not available due to insufficient follow-up to allow estimation.
Median PFS Time Based on Different Subgroups EGFR wild-type (n=67,69)	5.9 months Interval 5.0 to 7.0	7.1 months Interval 4.0 to 8.0
Median PFS Time Based on Different Subgroups KRAS mutation (n=11,10)	4.5 months Interval 1.9 to 7.2	6.0 months Interval 2.4 to 8.9
Median PFS Time Based on Different Subgroups KRAS wild-type (n=101,101)	6.8 months Interval 5.6 to 7.3	8.0 months Interval 7.5 to 10.8
Median PFS Time Based on Different Subgroups EGFR IHC positive (n=36,40)	6.0 months Interval 3.7 to 8.8	8.1 months Interval 7.4 to 11.0
Median PFS Time Based on Different Subgroups EGFR FISH positive (n=20,14)	5.9 months Interval 2.2 to 9.3	12.9 months Interval 9.4 to Estimate not available due to insufficient follow-up to allow estimation.
Median PFS Time Based on Different Subgroups EGFR FISH negative (n=23,25)	6.0 months Interval 4.6 to 8.8	7.5 months Interval 6.2 to 9.7

SECONDARY outcome

Timeframe: Randomization until death (assessed at baseline and every 8 weeks thereafter until death or end of study [up to approximately 5.5 years])

Population: FAS population. "n" is the number of participants evaluable under the specified category.

OS was defined as the time between the date of randomization and the date of death from any cause. Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. Participants with no post baseline information were censored at the time of randomization. OS among different subgroups of type of carcinoma, smoking habit, EGFR mutation type, KRAS mutation type, EGFR IHC test result type, and EGFR FISH result type. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Median Overall Survival (OS) Time-Overall and Among Different Subgroups Never smoked (n=107,112)	17.5 months Interval 14.8 to 21.7	25.9 months Interval 21.6 to 32.4
Median Overall Survival (OS) Time-Overall and Among Different Subgroups Overall participants (n=225,226)	15.2 months Interval 12.7 to 17.5	18.2 months Interval 16.3 to 20.8
Median Overall Survival (OS) Time-Overall and Among Different Subgroups Adenocarcinoma (n=168,174)	15.8 months Interval 13.6 to 18.5	20.9 months Interval 18.3 to 25.9
Median Overall Survival (OS) Time-Overall and Among Different Subgroups Non-adenocarcinoma (n=57,52)	12.4 months Interval 9.9 to 16.8	10.3 months Interval 7.6 to 13.0
Median Overall Survival (OS) Time-Overall and Among Different Subgroups Current/former smoker (n=118,114)	13.0 months Interval 11.0 to 15.8	13.0 months Interval 10.0 to 16.3
Median Overall Survival (OS) Time-Overall and Among Different Subgroups EGFR mutation (n=48,49)	20.6 months Interval 14.2 to 31.1	30.3 months Interval 22.2 to 37.1
Median Overall Survival (OS) Time-Overall and Among Different Subgroups EGFR wild-type (n=67,69)	12.2 months Interval 8.9 to 14.7	14.9 months Interval 12.2 to 18.2
Median Overall Survival (OS) Time-Overall and Among Different Subgroups KRAS mutation (n=11,10)	11.2 months Interval 5.7 to 16.5	17.5 months Interval 6.3 to 18.8
Median Overall Survival (OS) Time-Overall and Among Different Subgroups KRAS wild-type (n=101,101)	14.1 months Interval 12.4 to 18.2	18.1 months Interval 15.4 to 22.2
Median Overall Survival (OS) Time-Overall and Among Different Subgroups EGFR IHC positive (n=36,40)	15.2 months Interval 12.1 to 19.6	18.6 months Interval 16.3 to 32.4
Median Overall Survival (OS) Time-Overall and Among Different Subgroups EGFR IHC negative (n=25,12)	12.5 months Interval 7.8 to 19.8	21.9 months Interval 14.3 to Estimate not available due to insufficient follow-up to allow estimation.
Median Overall Survival (OS) Time-Overall and Among Different Subgroups EGFR FISH positive (n=20,14)	17.7 months Interval 8.9 to 23.8	43.1 months Interval 18.6 to Estimate not available due to insufficient follow-up to allow estimation.
Median Overall Survival (OS) Time-Overall and Among Different Subgroups EGFR FISH negative (n=23,25)	12.5 months Interval 10.3 to 16.0	16.7 months Interval 13.1 to 22.4

SECONDARY outcome

Timeframe: Randomization until death (assessed at baseline and every 8 weeks thereafter until death or end of study [up to approximately 5.5 years])

Population: FAS population. "n" is the number of participants evaluable under the specified category.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups Overall participants (n=225,226)	13.3 percentage of participants	15.9 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups Adenocarcinoma (n=168,174)	14.9 percentage of participants	19.5 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups Non-adenocarcinoma (n=57,52)	8.8 percentage of participants	3.8 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups Never smoked (n=107,112)	13.1 percentage of participants	23.2 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups Current/former smoker (n=118,114)	13.6 percentage of participants	8.8 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups EGFR mutation (n=48,49)	22.9 percentage of participants	30.6 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups EGFR wild-type (n=67,69)	7.5 percentage of participants	10.1 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups KRAS mutation (n=11,10)	0.0 percentage of participants	20.0 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups KRAS wild-type (n=101,101)	14.9 percentage of participants	17.8 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups EGFR IHC positive (n=36,40)	11.1 percentage of participants	25.0 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups EGFR IHC negative (n=25,12)	8.0 percentage of participants	33.3 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups EGFR FISH positive (n=20,14)	10.0 percentage of participants	42.9 percentage of participants
Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups EGFR FISH negative (n=23,25)	13.0 percentage of participants	16.0 percentage of participants

SECONDARY outcome

Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Population: FAS population.

Tumor response was evaluated according to RECIST (version 1.0). CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the screening sum LD; SD for target lesions is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and SD for non-target lesions defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. Responses were confirmed with repeated assessment 4 weeks after initial response was observed.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Non-Progression Rate: Percentage of Participants With a Confirmed Best Overall Response of Either Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for At Least 16 Weeks	64.4 percentage of participants Interval 57.8 to 70.7	67.3 percentage of participants Interval 60.7 to 73.3

SECONDARY outcome

Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Population: FAS population.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Objective Response Rate: Percentage of Participants With a Confirmed Best Overall Response of CR or PR	17.8 percentage of participants Interval 13.0 to 23.4	42.9 percentage of participants Interval 36.4 to 49.7

SECONDARY outcome

Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Population: FAS population participants who were responders (CR or PR).

Duration of response is defined as the time between the date of first documented response (CR or PR, as determined by the RECIST criteria) and the date of first documented PD or death. Participants who did not progress or die after they had a confirmed response (CR or PR) were censored at the date of their last tumor assessment where non-progression was documented or last date of follow-up for progression of disease, whichever was last. CR and PR are defined in Outcome Measure 7.

Outcome measures

Outcome measures
Measure	Placebo n=40 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=97 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Duration of Response	5.6 months Interval 5.0 to 6.0	10.3 months Interval 7.0 to 13.0

SECONDARY outcome

Timeframe: Randomization until PD (assessed at baseline and every 8 weeks thereafter until PD or end of study [up to approximately 1.5 years])

Population: FAS population.

Time to progression is defined as the time between the date of randomization and the date of the first documented disease progression. Participants who have not progressed at the time of study completion (or data cut off) or who were lost to follow up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow-up for progression of disease, whichever was latest. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Participants with no post baseline tumor assessments were censored at the time of randomization. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Time to Progression	6.5 months Interval 6.0 to 7.0	7.9 months Interval 7.0 to 9.0

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Population: FAS population.

LCS scores were obtained from a 7-item questionnaire from the Functional Assessment of Cancer Therapy - Lung (FACT-L) (version 4.0). Participants responded to questions such as shortness of breath, cough, tightness in chest, breathing difficulty, appetite loss, weight loss and unclear thinking; on a 5-point scale from 0-4, where 0 equaled (=) "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 (most symptomatic) to 28 (asymptomatic); higher score indicates fewer symptoms. A clinically meaningful decline used to determine symptomatic progression in this study was at least a three point decline in LCS score from baseline. Participants without symptomatic progression at the time of analysis were censored at the time of the last FACT-L assessment.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Percentage of Participants With Symptomatic Progression Assessed Using the Lung Cancer Subscale (LCS)	72.4 percentage of participants	66.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Population: FAS population.

Time to symptomatic progression was the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. LCS scores were obtained from a 7-item questionnaire from the FACT-L (version 4.0). Participants responded to questions such as shortness of breath, cough, tightness in chest, breathing difficulty, appetite loss, weight loss and unclear thinking; on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 (most symptomatic) to 28 (asymptomatic); higher score indicates fewer symptoms. A clinically meaningful decline used to determine symptomatic progression in this study was at least a three point decline in LCS score from baseline. Participants without symptomatic progression at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Time to Symptomatic Progression	6.6 months Interval 6.0 to 9.0	7.2 months Interval 6.0 to 10.0

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Population: FAS population.

TOI was defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 84; higher score indicates better physical aspects of quality of life (QoL). A clinically meaningful decline used to determine deterioration in TOI was greater than or equal to (≥) 6-point decline from baseline. Participants without deterioration in TOI at the time of analysis were censored at the time of the last FACT-L assessment.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Percentage of Participants With Deterioration in Trial Outcome Index (TOI) Using FACT-L Version 4.0	75.6 percentage of participants	65.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Population: FAS population.

Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. TOI is defined as the sum of the scores of the PWB, FWB, and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 84; higher score indicates better physical aspects of QoL. A clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline. Participants without deterioration in TOI at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Time to Deterioration in TOI Using FACT-L Version 4.0	5.6 months Interval 4.0 to 7.0	6.3 months Interval 5.0 to 8.0

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Population: FAS population.

Total FACT-L score was defined as the sum of the TOI, Social Well Being (SWB) and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 136; higher score indicates better QoL. A clinically meaningful decline used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Percentage of Participants With Deterioration in Quality of Life (QOL) Using FACT-L Version 4.0	79.6 percentage of participants	70.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Population: FAS population.

Time to deterioration in QoL is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in Total FACT-L or death on study. Total FACT-L score was defined as the sum of the TOI, SWB and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 136; higher score indicates better QoL. A clinically meaningful decline used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Time to Deterioration in QOL Using FACT-L Version 4.0	4.5 months Interval 4.0 to 6.0	5.6 months Interval 4.0 to 7.0

SECONDARY outcome

Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 5.5 years])

Population: FAS population.

Median follow-up was calculated using 'Reverse Kaplan-Meier' analysis for Overall survival.

Outcome measures

Outcome measures
Measure	Placebo n=225 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 Participants Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Median Follow-up Time During the Study	50.3 months Interval 47.6 to 52.5	50.2 months Interval 48.2 to 51.7

Adverse Events

Placebo

Serious events: 76 serious events

Other events: 217 other events

Deaths: 0 deaths

Erlotinib

Serious events: 70 serious events

Other events: 223 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=222 participants at risk Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral placebo daily from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from placebo could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants had the option to be crossed over to open-label erlotinib 150 mg/day outside the study (Off-study phase).	Erlotinib n=226 participants at risk Participants received 1250 mg/m\^2 of gemcitabine IV infusion on Day 1 and 8, carboplatin 5x AUC or cisplatin 75 mg/m\^2 IV infusion on Day 1 and oral erlotinib 150 mg/day from Day 15 to 28 every 4 weeks, continued for 6 cycles (28-day cycle) until PD, unacceptable toxicity or death in the primary study treatment phase. Participants who completed 6 cycles of treatment without PD or unacceptable toxicity, or if they withdrew early because of toxicity from the platinum-doublet chemotherapy, entered the post-study treatment phase and continued same treatment until PD, unacceptable toxicity or death. Participants who withdrew due to PD or toxicity from erlotinib could not enter the post-study treatment phase. Upon PD (during either the primary or post-study treatment phase), participants were treated at the discretion of the investigators' discretion (Off-study phase).
Blood and lymphatic system disorders Neutropenia	49.5% 110/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	50.4% 114/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Blood and lymphatic system disorders Leukopenia	23.0% 51/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	18.6% 42/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Blood and lymphatic system disorders Anaemia	43.2% 96/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	38.5% 87/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Blood and lymphatic system disorders Thrombocytopenia	20.7% 46/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	19.9% 45/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Gastrointestinal disorders Nausea	41.4% 92/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	39.8% 90/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Gastrointestinal disorders Vomiting	30.6% 68/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	30.5% 69/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Gastrointestinal disorders Diarrhoea	15.3% 34/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	30.5% 69/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Gastrointestinal disorders Constipation	20.7% 46/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	20.8% 47/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Gastrointestinal disorders Stomatitis	3.6% 8/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	11.9% 27/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Gastrointestinal disorders Mouth ulceration	0.90% 2/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	6.6% 15/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Gastrointestinal disorders Dyspepsia	6.3% 14/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	1.8% 4/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Gastrointestinal disorders Abdominal distension	2.3% 5/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	5.8% 13/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Skin and subcutaneous tissue disorders Rash	32.4% 72/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	62.8% 142/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Skin and subcutaneous tissue disorders Alopecia	23.0% 51/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	18.1% 41/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Skin and subcutaneous tissue disorders Pruritus	9.5% 21/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	11.9% 27/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Skin and subcutaneous tissue disorders Dermatitis acneiform	5.4% 12/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	14.6% 33/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Skin and subcutaneous tissue disorders Dry skin	4.1% 9/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	15.0% 34/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
General disorders Fatigue	27.0% 60/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	24.3% 55/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
General disorders Pyrexia	11.3% 25/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	16.4% 37/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
General disorders Asthenia	7.2% 16/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	7.1% 16/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
General disorders Mucosal inflammation	5.9% 13/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	10.6% 24/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
General disorders Chest pain	9.5% 21/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	10.6% 24/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
General disorders Malaise	4.5% 10/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	5.3% 12/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Metabolism and nutrition disorders Decreased appetite	41.4% 92/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	35.0% 79/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Metabolism and nutrition disorders Hypokalaemia	5.4% 12/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	7.5% 17/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Respiratory, thoracic and mediastinal disorders Cough	15.8% 35/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	16.4% 37/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.7% 26/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	11.1% 25/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Respiratory, thoracic and mediastinal disorders Haemoptysis	8.6% 19/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	8.0% 18/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Respiratory, thoracic and mediastinal disorders Hiccups	6.3% 14/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	3.5% 8/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.2% 7/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	5.8% 13/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.7% 6/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	5.8% 13/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Respiratory, thoracic and mediastinal disorders Productive cough	2.3% 5/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	5.3% 12/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Investigations Alanine aminotransferase increased	8.6% 19/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	7.1% 16/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Investigations White blood cell count decreased	5.9% 13/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	4.4% 10/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Investigations Aspartate aminotransferase increased	5.4% 12/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	4.9% 11/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Investigations Weight decreased	3.2% 7/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	5.8% 13/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Musculoskeletal and connective tissue disorders Back pain	9.9% 22/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	9.7% 22/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.0% 11/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	8.8% 20/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Musculoskeletal and connective tissue disorders Myalgia	5.4% 12/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	3.5% 8/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Nervous system disorders Dizziness	9.0% 20/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	10.2% 23/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Nervous system disorders Headache	8.1% 18/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	6.2% 14/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Psychiatric disorders Insomnia	16.7% 37/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	20.4% 46/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Infections and infestations Upper respiratory tract infection	4.1% 9/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	7.1% 16/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Infections and infestations Nasopharyngitis	5.4% 12/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	4.4% 10/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)
Infections and infestations Paronychia	0.00% 0/222 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)	6.6% 15/226 • Up to 28 days after the last dose in the primary and post study treatment phases of the study (up to approximately 5.5 years)