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

• ClinicalTrials.gov Identifier: NCT00883779
• Recruitment Status: Completed
• First Posted: April 20, 2009
• Results First Posted: December 14, 2015
• Last Update Posted: December 14, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Non-Squamous Non-Small Cell Lung Cancer
• Interventions: Drug: Placebo; Drug: Platinum chemotherapy (cisplatin or carboplatin); Drug: erlotinib [Tarceva]; Drug: gemcitabine
• Enrollment: 451

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description	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).	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).
Period Title: Primary Study Treatment Phase
Started	225	226
Completed	120	140
Not Completed	105	86
Reason Not Completed
Did not receive allocated intervention	4	4
Disease progression	75	59
Adverse Event	16	16
Death	2	3
Refused Treatment	5	4
Other	3	0
Period Title: Post-Study Treatment Phase
Started	112	135
Completed	0	0
Not Completed	112	135
Reason Not Completed
Adverse Event	2	3
Death	1	3
Protocol Violation	0	1
Refused Treatment	3	0
Disease progression	103	122
Other	3	0
Ongoing in the study	0	6
Period Title: Off-study Phase
Started	209	202
Completed	0	0
Not Completed	209	202
Reason Not Completed
Death	185	174
Refused treatment	1	1
Failure to return	5	6
Other	18	21

Baseline Characteristics

Arm/Group Title		Placebo	Erlotinib	Total
Arm/Group Description		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).	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 of all reporting groups
Overall Number of Baseline Participants		225	226	451
Baseline Analysis Population Description		Full analysis set (FAS) population (Included all enrolled participants).
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	225 participants	226 participants	451 participants
		56.4 (11.08)	57.2 (9.71)	56.8 (10.41)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	225 participants	226 participants	451 participants
	Female	85 37.8%	94 41.6%	179 39.7%
	Male	140 62.2%	132 58.4%	272 60.3%

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival (PFS) Time
Description	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.
Time Frame	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])

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Median (95% Confidence Interval); Unit of Measure: months
	6.0; (6.0 to 7.0)	7.6; (7.0 to 8.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.70
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants Alive and Free From Disease Progression
Description	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.
Time Frame	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])

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Measure Type: Number; Unit of Measure: percentage of participants
	6.2	22.6

3. Secondary Outcome

Title	Median PFS Time Based on Different Subgroups
Description	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.
Time Frame	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])

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Median (95% Confidence Interval); Unit of Measure: months
Adenocarcinoma (n=168,174)	6.5; (6 to 7)	8.2; (8 to 11)
Non-adenocarcinoma (n=57,52)	5.8; (5 to 7)	5.7; (3 to 7)
Never smoked (n=107,112)	6.6; (5 to 7)	10.9; (9 to 14)
Former/current smoker (n=118,114)	5.9; (5.5 to 7.1)	5.7; (4 to 7)
EGFR mutation (n=48,49)	6.9; (5 to 8)	15.6 [1]; (13 to NA)
EGFR wild-type (n=67,69)	5.9; (5 to 7)	7.1; (4 to 8)
KRAS mutation (n=11,10)	4.5; (1.9 to 7.2)	6.0; (2.4 to 8.9)
KRAS wild-type (n=101,101)	6.8; (5.6 to 7.3)	8.0; (7.5 to 10.8)
EGFR IHC positive (n=36,40)	6.0; (3.7 to 8.8)	8.1; (7.4 to 11.0)
EGFR IHC negative (n=25,12)	6.7; (4.6 to 7.6)	10.1; (7.6 to 15.6)
EGFR FISH positive (n=20,14)	5.9; (2.2 to 9.3)	12.9 [1]; (9.4 to NA)
EGFR FISH negative (n=23,25)	6.0; (4.6 to 8.8)	7.5; (6.2 to 9.7)

[1]

Estimate not available due to insufficient follow-up to allow estimation.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in adenocarcinoma subgroup
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.39 to 0.64
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in non-adenocarcinoma subgroup
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.579
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.33
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in never smoked subgroup
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.53
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in former/current smoker subgroup
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.2067
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.10
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in subgroup EGFR mutation
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.35
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in subgroup EGFR wild-type
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.7511
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.34
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in subgroup KRAS mutation
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.3169
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.25 to 1.58
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in subgroup KRAS wild-type
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; 0.37 to 0.70
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in subgroup EGFR IHC positive
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0091
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; 0.31 to 0.86
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in subgroup EGFR IHC negative
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0179
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95%; 0.18 to 0.88
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in subgroup EGFR FISH positive
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0017
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; 0.11 to 0.64
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	PFS in subgroup EGFR FISH negative
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1880
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.37 to 1.22
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Median Overall Survival (OS) Time-Overall and Among Different Subgroups
Description	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.
Time Frame	Randomization until death (assessed at baseline and every 8 weeks thereafter until death or end of study [up to approximately 5.5 years])

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Median (95% Confidence Interval); Unit of Measure: months
Overall participants (n=225,226)	15.2; (12.7 to 17.5)	18.2; (16.3 to 20.8)
Adenocarcinoma (n=168,174)	15.8; (13.6 to 18.5)	20.9; (18.3 to 25.9)
Non-adenocarcinoma (n=57,52)	12.4; (9.9 to 16.8)	10.3; (7.6 to 13.0)
Never smoked (n=107,112)	17.5; (14.8 to 21.7)	25.9; (21.6 to 32.4)
Current/former smoker (n=118,114)	13.0; (11.0 to 15.8)	13.0; (10.0 to 16.3)
EGFR mutation (n=48,49)	20.6; (14.2 to 31.1)	30.3; (22.2 to 37.1)
EGFR wild-type (n=67,69)	12.2; (8.9 to 14.7)	14.9; (12.2 to 18.2)
KRAS mutation (n=11,10)	11.2; (5.7 to 16.5)	17.5; (6.3 to 18.8)
KRAS wild-type (n=101,101)	14.1; (12.4 to 18.2)	18.1; (15.4 to 22.2)
EGFR IHC positive (n=36,40)	15.2; (12.1 to 19.6)	18.6; (16.3 to 32.4)
EGFR IHC negative (n=25,12)	12.5; (7.8 to 19.8)	21.9 [1]; (14.3 to NA)
EGFR FISH positive (n=20,14)	17.7; (8.9 to 23.8)	43.1 [1]; (18.6 to NA)
EGFR FISH negative (n=23,25)	12.5; (10.3 to 16.0)	16.7; (13.1 to 22.4)

[1]

Estimate not available due to insufficient follow-up to allow estimation.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in overall participants (FAS population)
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1213
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.04
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup adenocarcinoma
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0356
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.62 to 0.98
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup non-adenocarcinoma
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1157
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95%; 0.92 to 2.03
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup never smoked
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0056
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.49 to 0.89
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup current/former smoker
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.3473
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.50
	Estimation Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup EGFR mutation
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1614
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.45 to 1.14
	Estimation Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup EGFR wild-type
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1691
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.78
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.11
	Estimation Comments	[Not Specified]

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup KRAS mutation
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1415
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.19 to 1.28
	Estimation Comments	[Not Specified]

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup KRAS wild-type
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1447
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.80
	Confidence Interval	(2-Sided) 95%; 0.59 to 1.08
	Estimation Comments	[Not Specified]

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in EGFR IHC positive
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0310
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.35 to 0.96
	Estimation Comments	[Not Specified]

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS in subgroup EGFR IHC negative
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0581
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.21 to 1.05
	Estimation Comments	[Not Specified]

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS of subgroup EGFR FISH positive
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0063
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; 0.14 to 0.75
	Estimation Comments	[Not Specified]

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	OS of subgroup EGFR FISH negative
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.3268
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.40 to 1.36
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups
Description	[Not Specified]
Time Frame	Randomization until death (assessed at baseline and every 8 weeks thereafter until death or end of study [up to approximately 5.5 years])

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Measure Type: Number; Unit of Measure: percentage of participants
Overall participants (n=225,226)	13.3	15.9
Adenocarcinoma (n=168,174)	14.9	19.5
Non-adenocarcinoma (n=57,52)	8.8	3.8
Never smoked (n=107,112)	13.1	23.2
Current/former smoker (n=118,114)	13.6	8.8
EGFR mutation (n=48,49)	22.9	30.6
EGFR wild-type (n=67,69)	7.5	10.1
KRAS mutation (n=11,10)	0.0	20.0
KRAS wild-type (n=101,101)	14.9	17.8
EGFR IHC positive (n=36,40)	11.1	25.0
EGFR IHC negative (n=25,12)	8.0	33.3
EGFR FISH positive (n=20,14)	10.0	42.9
EGFR FISH negative (n=23,25)	13.0	16.0

6. Secondary Outcome

Title	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
Description	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.
Time Frame	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])

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	64.4; (57.8 to 70.7)	67.3; (60.7 to 73.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	Difference in non-progression response rates
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.5289
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.81
	Confidence Interval	(2-Sided) 95%; -6.2 to 11.8
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	Objective Response Rate: Percentage of Participants With a Confirmed Best Overall Response of CR or PR
Description	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. Responses were confirmed with repeated assessment 4 weeks after initial response was observed.
Time Frame	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])

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	17.8; (13.0 to 23.4)	42.9; (36.4 to 49.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	Difference in objective response rates
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	25.14
	Confidence Interval	(2-Sided) 95%; 16.7 to 33.5
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Duration of Response
Description	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.
Time Frame	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])

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	40	97
Median (95% Confidence Interval); Unit of Measure: months
	5.6; (5 to 6)	10.3; (7 to 13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; 0.21 to 0.50
	Estimation Comments	[Not Specified]

9. Secondary Outcome

Title	Time to Progression
Description	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.
Time Frame	Randomization until PD (assessed at baseline and every 8 weeks thereafter until PD or end of study [up to approximately 1.5 years])

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Median (95% Confidence Interval); Unit of Measure: months
	6.5; (6 to 7)	7.9; (7 to 9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.69
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Percentage of Participants With Symptomatic Progression Assessed Using the Lung Cancer Subscale (LCS)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Measure Type: Number; Unit of Measure: percentage of participants
	72.4	66.4

11. Secondary Outcome

Title	Time to Symptomatic Progression
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Mean (95% Confidence Interval); Unit of Measure: months
	6.6; (6 to 9)	7.2; (6 to 10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0364
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.63 to 0.99
	Estimation Comments	[Not Specified]

12. Secondary Outcome

Title	Percentage of Participants With Deterioration in Trial Outcome Index (TOI) Using FACT-L Version 4.0
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Measure Type: Number; Unit of Measure: percentage of participants
	75.6	65.9

13. Secondary Outcome

Title	Time to Deterioration in TOI Using FACT-L Version 4.0
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Median (95% Confidence Interval); Unit of Measure: months
	5.6; (4 to 7)	6.3; (5 to 8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0181
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.61 to 0.96
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Percentage of Participants With Deterioration in Quality of Life (QOL) Using FACT-L Version 4.0
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Measure Type: Number; Unit of Measure: percentage of participants
	79.6	70.4

15. Secondary Outcome

Title	Time to Deterioration in QOL Using FACT-L Version 4.0
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Median (95% Confidence Interval); Unit of Measure: months
	4.5; (4 to 6)	5.6; (4 to 7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0035
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio, log
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.59 to 0.90
	Estimation Comments	[Not Specified]

16. Secondary Outcome

Title	Median Follow-up Time During the Study
Description	Median follow-up was calculated using 'Reverse Kaplan-Meier' analysis for Overall survival.
Time Frame	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])

Outcome Measure Data

Analysis Population Description

FAS population.

Arm/Group Title	Placebo	Erlotinib
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	225	226
Median (95% Confidence Interval); Unit of Measure: months
	50.3; (47.6 to 52.5)	50.2; (48.2 to 51.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Erlotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9130
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.60 to 1.59
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	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)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo	Erlotinib
Arm/Group Description	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).	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).
All-Cause Mortality
	Placebo	Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Placebo	Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	76/222 (34.23%)	70/226 (30.97%)
Blood and lymphatic system disorders
Anaemia * 1	26/222 (11.71%)	22/226 (9.73%)
Thrombocytopenia * 1	16/222 (7.21%)	10/226 (4.42%)
Neutropenia * 1	2/222 (0.90%)	4/226 (1.77%)
Febrile neutropenia * 1	3/222 (1.35%)	2/226 (0.88%)
Bone marrow failure * 1	2/222 (0.90%)	1/226 (0.44%)
Leukopenia * 1	1/222 (0.45%)	1/226 (0.44%)
Cardiac disorders
Acute myocardial infarction * 1	1/222 (0.45%)	0/226 (0.00%)
Myocardial infarction * 1	0/222 (0.00%)	1/226 (0.44%)
Palpitations * 1	0/222 (0.00%)	1/226 (0.44%)
Pericardial effusion * 1	0/222 (0.00%)	1/226 (0.44%)
Ventricular extrasystoles * 1	1/222 (0.45%)	0/226 (0.00%)
Ear and labyrinth disorders
Vertigo * 1	0/222 (0.00%)	3/226 (1.33%)
Gastrointestinal disorders
Vomiting * 1	3/222 (1.35%)	2/226 (0.88%)
Diarrhoea * 1	2/222 (0.90%)	1/226 (0.44%)
Abdominal pain * 1	2/222 (0.90%)	0/226 (0.00%)
Ileus * 1	1/222 (0.45%)	1/226 (0.44%)
Abdominal pain lower * 1	1/222 (0.45%)	0/226 (0.00%)
Constipation * 1	0/222 (0.00%)	1/226 (0.44%)
Lower gastrointestinal haemorrhage * 1	0/222 (0.00%)	1/226 (0.44%)
Melaena * 1	0/222 (0.00%)	1/226 (0.44%)
Oesophageal compression * 1	1/222 (0.45%)	0/226 (0.00%)
Rectal haemorrhage * 1	1/222 (0.45%)	0/226 (0.00%)
General disorders
Pyrexia * 1	2/222 (0.90%)	3/226 (1.33%)
Asthenia * 1	1/222 (0.45%)	1/226 (0.44%)
Chest pain * 1	0/222 (0.00%)	1/226 (0.44%)
Fatigue * 1	1/222 (0.45%)	0/226 (0.00%)
Pain * 1	1/222 (0.45%)	0/226 (0.00%)
Thrombosis in device * 1	0/222 (0.00%)	1/226 (0.44%)
Hepatobiliary disorders
Cholecystitis * 1	1/222 (0.45%)	0/226 (0.00%)
Liver injury * 1	1/222 (0.45%)	0/226 (0.00%)
Infections and infestations
Pneumonia * 1	9/222 (4.05%)	7/226 (3.10%)
Cellulitis * 1	1/222 (0.45%)	2/226 (0.88%)
Lower respiratory tract infection * 1	1/222 (0.45%)	2/226 (0.88%)
Pneumonia bacterial * 1	2/222 (0.90%)	1/226 (0.44%)
Sepsis * 1	1/222 (0.45%)	2/226 (0.88%)
Appendicitis * 1	0/222 (0.00%)	1/226 (0.44%)
Bronchitis * 1	2/222 (0.90%)	0/226 (0.00%)
Gastroenteritis * 1	2/222 (0.90%)	0/226 (0.00%)
Pneumonia viral * 1	1/222 (0.45%)	1/226 (0.44%)
Device related infection * 1	0/222 (0.00%)	1/226 (0.44%)
Gastroenteritis bacterial * 1	0/222 (0.00%)	1/226 (0.44%)
Infection * 1	1/222 (0.45%)	0/226 (0.00%)
Lung abscess * 1	1/222 (0.45%)	0/226 (0.00%)
Lung infection * 1	0/222 (0.00%)	1/226 (0.44%)
Ophthalmic herpes zoster * 1	1/222 (0.45%)	0/226 (0.00%)
Pulmonary sepsis * 1	1/222 (0.45%)	0/226 (0.00%)
Urinary tract infection * 1	1/222 (0.45%)	0/226 (0.00%)
Injury, poisoning and procedural complications
Multiple injuries * 1	0/222 (0.00%)	1/226 (0.44%)
Investigations
Blood creatinine increased * 1	0/222 (0.00%)	2/226 (0.88%)
White blood cell count decreased * 1	1/222 (0.45%)	0/226 (0.00%)
Metabolism and nutrition disorders
Cachexia * 1	0/222 (0.00%)	1/226 (0.44%)
Dehydration * 1	0/222 (0.00%)	1/226 (0.44%)
Hypokalaemia * 1	0/222 (0.00%)	1/226 (0.44%)
Musculoskeletal and connective tissue disorders
Muscular weakness * 1	1/222 (0.45%)	1/226 (0.44%)
Bone pain * 1	1/222 (0.45%)	0/226 (0.00%)
Musculoskeletal chest pain * 1	0/222 (0.00%)	1/226 (0.44%)
Osteoarthritis * 1	0/222 (0.00%)	1/226 (0.44%)
Pathological fracture * 1	1/222 (0.45%)	0/226 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hodgkin's disease * 1	0/222 (0.00%)	1/226 (0.44%)
Lymphangiosis carcinomatosa * 1	1/222 (0.45%)	0/226 (0.00%)
Non-small cell lung cancer metastatic * 1	0/222 (0.00%)	1/226 (0.44%)
Nervous system disorders
Altered state of consciousness * 1	0/222 (0.00%)	1/226 (0.44%)
Ataxia * 1	1/222 (0.45%)	0/226 (0.00%)
Cerebrovascular accident * 1	0/222 (0.00%)	1/226 (0.44%)
Paraparesis * 1	0/222 (0.00%)	1/226 (0.44%)
Pyramidal tract syndrome * 1	0/222 (0.00%)	1/226 (0.44%)
Vocal cord paralysis * 1	1/222 (0.45%)	0/226 (0.00%)
Psychiatric disorders
Agitation * 1	1/222 (0.45%)	0/226 (0.00%)
Confusional state * 1	0/222 (0.00%)	1/226 (0.44%)
Transient psychosis * 1	0/222 (0.00%)	1/226 (0.44%)
Renal and urinary disorders
Renal failure * 1	1/222 (0.45%)	0/226 (0.00%)
Renal ischaemia * 1	0/222 (0.00%)	1/226 (0.44%)
Tubulointerstitial nephritis * 1	0/222 (0.00%)	1/226 (0.44%)
Urinary incontinence * 1	0/222 (0.00%)	1/226 (0.44%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	6/222 (2.70%)	4/226 (1.77%)
Pleural effusion * 1	1/222 (0.45%)	3/226 (1.33%)
Haemoptysis * 1	0/222 (0.00%)	3/226 (1.33%)
Pneumonia aspiration * 1	2/222 (0.90%)	0/226 (0.00%)
Pulmonary embolism * 1	0/222 (0.00%)	2/226 (0.88%)
Acute respiratory distress syndrome * 1	0/222 (0.00%)	1/226 (0.44%)
Acute respiratory failure * 1	1/222 (0.45%)	0/226 (0.00%)
Dyspnoea exertional * 1	0/222 (0.00%)	1/226 (0.44%)
Orthopnoea * 1	0/222 (0.00%)	1/226 (0.44%)
Respiratory failure * 1	1/222 (0.45%)	0/226 (0.00%)
Skin and subcutaneous tissue disorders
Rash * 1	0/222 (0.00%)	1/226 (0.44%)
Vascular disorders
Superior vena cava occlusion * 1	0/222 (0.00%)	1/226 (0.44%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (17.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Erlotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	217/222 (97.75%)	223/226 (98.67%)
Blood and lymphatic system disorders
Neutropenia * 1	110/222 (49.55%)	114/226 (50.44%)
Leukopenia * 1	51/222 (22.97%)	42/226 (18.58%)
Anaemia * 1	96/222 (43.24%)	87/226 (38.50%)
Thrombocytopenia * 1	46/222 (20.72%)	45/226 (19.91%)
Gastrointestinal disorders
Nausea * 1	92/222 (41.44%)	90/226 (39.82%)
Vomiting * 1	68/222 (30.63%)	69/226 (30.53%)
Diarrhoea * 1	34/222 (15.32%)	69/226 (30.53%)
Constipation * 1	46/222 (20.72%)	47/226 (20.80%)
Stomatitis * 1	8/222 (3.60%)	27/226 (11.95%)
Mouth ulceration * 1	2/222 (0.90%)	15/226 (6.64%)
Dyspepsia * 1	14/222 (6.31%)	4/226 (1.77%)
Abdominal distension * 1	5/222 (2.25%)	13/226 (5.75%)
General disorders
Fatigue * 1	60/222 (27.03%)	55/226 (24.34%)
Pyrexia * 1	25/222 (11.26%)	37/226 (16.37%)
Asthenia * 1	16/222 (7.21%)	16/226 (7.08%)
Mucosal inflammation * 1	13/222 (5.86%)	24/226 (10.62%)
Chest pain * 1	21/222 (9.46%)	24/226 (10.62%)
Malaise * 1	10/222 (4.50%)	12/226 (5.31%)
Infections and infestations
Upper respiratory tract infection * 1	9/222 (4.05%)	16/226 (7.08%)
Nasopharyngitis * 1	12/222 (5.41%)	10/226 (4.42%)
Paronychia * 1	0/222 (0.00%)	15/226 (6.64%)
Investigations
Alanine aminotransferase increased * 1	19/222 (8.56%)	16/226 (7.08%)
White blood cell count decreased * 1	13/222 (5.86%)	10/226 (4.42%)
Aspartate aminotransferase increased * 1	12/222 (5.41%)	11/226 (4.87%)
Weight decreased * 1	7/222 (3.15%)	13/226 (5.75%)
Metabolism and nutrition disorders
Decreased appetite * 1	92/222 (41.44%)	79/226 (34.96%)
Hypokalaemia * 1	12/222 (5.41%)	17/226 (7.52%)
Musculoskeletal and connective tissue disorders
Back pain * 1	22/222 (9.91%)	22/226 (9.73%)
Musculoskeletal pain * 1	11/222 (4.95%)	20/226 (8.85%)
Myalgia * 1	12/222 (5.41%)	8/226 (3.54%)
Nervous system disorders
Dizziness * 1	20/222 (9.01%)	23/226 (10.18%)
Headache * 1	18/222 (8.11%)	14/226 (6.19%)
Psychiatric disorders
Insomnia * 1	37/222 (16.67%)	46/226 (20.35%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	35/222 (15.77%)	37/226 (16.37%)
Dyspnoea * 1	26/222 (11.71%)	25/226 (11.06%)
Haemoptysis * 1	19/222 (8.56%)	18/226 (7.96%)
Hiccups * 1	14/222 (6.31%)	8/226 (3.54%)
Oropharyngeal pain * 1	7/222 (3.15%)	13/226 (5.75%)
Rhinorrhoea * 1	6/222 (2.70%)	13/226 (5.75%)
Productive cough * 1	5/222 (2.25%)	12/226 (5.31%)
Skin and subcutaneous tissue disorders
Rash * 1	72/222 (32.43%)	142/226 (62.83%)
Alopecia * 1	51/222 (22.97%)	41/226 (18.14%)
Pruritus * 1	21/222 (9.46%)	27/226 (11.95%)
Dermatitis acneiform * 1	12/222 (5.41%)	33/226 (14.60%)
Dry skin * 1	9/222 (4.05%)	34/226 (15.04%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (17.1)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-LaRoche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. doi: 10.1016/S1470-2045(13)70254-7. Epub 2013 Jun 17.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00883779
• Other Study ID Numbers: MO22201
• First Submitted: April 15, 2009
• First Posted: April 20, 2009
• Results First Submitted: November 10, 2015
• Results First Posted: December 14, 2015
• Last Update Posted: December 14, 2015