ARCHER 1009 : A Study Of Dacomitinib (PF-00299804) Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer (ARCHER 1009)

• ClinicalTrials.gov Identifier: NCT01360554
• Recruitment Status: Completed
• First Posted: May 25, 2011
• Results First Posted: May 24, 2017
• Last Update Posted: May 24, 2017
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer
• Interventions: Drug: Dacomitinib (PF-00299804); Drug: Active Comparator (erlotinib); Drug: Placebo erlotinib; Drug: Placebo PF00299804
• Enrollment: 878

Participant Flow

Recruitment Details	The study was conducted at 134 sites with 878 participants randomized in a 1:1 ratio to 1 of 2 treatment arms, of these 872 were treated. Eligible participants who provided written informed consent and met all inclusion and exclusion criteria were assigned a Single Subject Identification number and randomized by the central randomization system.
Pre-assignment Details	There were no significant study milestones following participant enrollment, but prior to group assignment.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Period Title: Overall Study
Started	439 [1]	439 [1]
Treated	436	436
Completed	0	0
Not Completed	439	439
Reason Not Completed
Death	359	371
Lost to Follow-up	4	4
Withdrawal by Subject	23	24
Study terminated by sponsor	49	37
Other, not specified	1	0
Randomized but not treated.	3	3
[1] Three participants were randomized but not treated.

Baseline Characteristics

Arm/Group Title		Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)	Total
Arm/Group Description		Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Total of all reporting groups
Overall Number of Baseline Participants		436	436	872
Baseline Analysis Population Description		The baseline analysis population included all treated participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	436 participants	436 participants	872 participants
		63.3 (9.57)	61.7 (9.71)	62.5 (9.67)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	436 participants	436 participants	872 participants
	Female	150 34.4%	161 36.9%	311 35.7%
	Male	286 65.6%	275 63.1%	561 64.3%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Per Independent Radiologic Review.
Description	PFS was defined as the time from randomization to the date of disease progression as by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	439	439
Median (95% Confidence Interval); Unit of Measure: Months
	2.6; (1.9 to 2.8)	2.5; (1.9 to 2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.195
	Comments	One-sided P-value.
	Method	1-sided stratified log-rank test
	Comments	Stratified by epidermal growth factor receptor (EGFR) status, Kirsten Rat Sarcoma status (KRAS), baseline Eastern Cooperative Oncology Group (ECOG).
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.933
	Confidence Interval	(2-Sided) 95%; 0.797 to 1.093
	Estimation Comments	The HR (Dacomitinib arm versus erlotinib arm) and 95% CI were estimated from stratified Cox regression with EGFR status, KRAS, baseline ECOG as stratification factors.

2. Primary Outcome

Title	Progression-Free Survival (PFS) Per Independent Radiologic Review in KRAS Wild-type (WT) Participants.
Description	PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Independent Radiologic Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Outcome Measure Data

Analysis Population Description

ITT population for KRAS-WT participants: all participants who were confirmed as having KRAS-WT tumors, randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	256	263
Median (95% Confidence Interval); Unit of Measure: Months
	2.6; (1.9 to 2.9)	2.5; (1.9 to 3.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.643
	Comments	One-sided P-value
	Method	1-sided stratified log-rank test
	Comments	Stratified by EGFR status and baseline ECOG.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.037
	Confidence Interval	(2-Sided) 95%; 0.848 to 1.268
	Estimation Comments	The HR (Dacomitinib arm versus erlotinib arm) and 95% CI were estimated from stratified Cox regression with EGFR status and baseline ECOG as stratification factors.

3. Secondary Outcome

Title	PFS Based on Investigator Review.
Description	PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Investigator's Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	439	439
Median (95% Confidence Interval); Unit of Measure: Months
	1.9; (1.9 to 2.6)	1.9; (1.8 to 2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.069
	Comments	Stratified by EGFR status, KRAS status, and baseline ECOG.
	Method	1-sided stratified log-rank test
	Comments	One-sided P-value
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.899
	Confidence Interval	(2-Sided) 95%; 0.780 to 1.035
	Estimation Comments	The HR (Dacomitinib arm versus erlotinib arm) and 95% CI were estimated from stratified Cox regression with EGFR status, KRAS status, and baseline ECOG as stratification factors.

4. Secondary Outcome

Title	PFS Based on Investigator Review in KRAS-WT Participants.
Description	PFS was defined as the time from randomization to the date of disease progression as by RECIST v1.1 per Investigator's Review or death due to any cause, whichever occurred first. Objective progression was defined as a 20% increase in the sum of the diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions, or the appearance of any new unequivocal malignant lesions. Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Outcome Measure Data

Analysis Population Description

ITT population for KRAS-WT participants: all participants who were confirmed as having KRAS-WT tumors, randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	256	263
Median (95% Confidence Interval); Unit of Measure: Months
	1.9; (1.8 to 2.7)	1.9; (1.8 to 2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.728
	Comments	One-sided P-value.
	Method	1-sided stratified log-rank test
	Comments	Stratified by EGFR status and baseline ECOG.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.057
	Confidence Interval	(2-Sided) 95%; 0.881 to 1.267
	Estimation Comments	The HR (Dacomitinib arm versus erlotinib arm) and 95% CI were estimated from stratified Cox regression with EGFR status and baseline ECOG as stratification factors.

5. Secondary Outcome

Title	Overall Survival (OS).
Description	OS was defined as the time from randomization to the date of death for any cause. In the absence of confirmation of death, survival time was censored at the last date the patient was known to be alive (ie, at their last known alive date from long term follow-up).
Time Frame	From date of randomization until the date of death from any cause or last date known to be alive, participants were followed up regardless of the reason for discontinuation from study treatment at intervals of no longer than every 2 months.

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	439	439
Median (95% Confidence Interval); Unit of Measure: Months
	7.9; (6.8 to 9.0)	8.3; (7.4 to 9.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.638
	Comments	One-sided P-value.
	Method	1-sided stratified log-rank test.
	Comments	Stratified by EGFR status, KRAS status, and baseline ECOG.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.026
	Confidence Interval	(2-Sided) 95%; 0.887 to 1.188
	Estimation Comments	The HR (Dacomitinib arm versus erlotinib arm) and 95% CI were estimated from stratified Cox regression with EGFR status, KRAS status, and baseline ECOG as stratification factors.

6. Secondary Outcome

Title	OS in KRAS-WT Participants.
Description	OS was defined as the time from randomization to the date of death for any cause. In the absence of confirmation of death, survival time was censored at the last date the patient was known to be alive (ie, at their last known alive date from long term follow-up). Tumor tissue from participants' original diagnostic biopsies or recently obtained biopsies were analyzed to determine KRAS status.
Time Frame	From date of randomization until the date of death from any cause or last date known to be alive, participants were followed up regardless of the reason for discontinuation from study treatment at intervals of no longer than every 2 months.

Outcome Measure Data

Analysis Population Description

ITT population for KRAS-WT participants: all participants who were confirmed as having KRAS-WT tumors, randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	256	263
Median (95% Confidence Interval); Unit of Measure: Months
	8.1; (6.7 to 9.4)	8.5; (7.5 to 10.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.775
	Comments	One-sided P-value.
	Method	1-sided stratified log-rank test.
	Comments	Stratified by EGFR status and baseline ECOG.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.078
	Confidence Interval	(2-Sided) 95%; 0.886 to 1.312
	Estimation Comments	The HR (Dacomitinib arm versus erlotinib arm) and 95% CI were estimated from stratified Cox regression with EGFR status and baseline ECOG as stratification factors.

7. Secondary Outcome

Title	Best Overall Response (BOR) Per Independent Radiologic Review.
Description	The BOR was the best response per RECIST (version 1.1) criteria as assessed by independent assessment recorded from randomization until disease progression. Per RECIST version 1.1: Complete Response (CR): disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; Partial Response (PR): >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; Progressive Disease (PD): >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
Time Frame	From date of randomization until progression or initiation of new anti-cancer therapy or death. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	439	439
Measure Type: Number; Unit of Measure: Participants
Complete response	6	8
Partial response	46	27
Stable/No response	163	182
Objective progression	151	146
Indeterminate	73	76

8. Secondary Outcome

Title	BOR Per Investigator Review.
Description	The BOR was the best response per RECIST (version 1.1) criteria as assessed by investigator assessment recorded from randomization until disease progression. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
Time Frame	From date of randomization until progression or initiation of new anti-cancer therapy or death. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Outcome Measure Data

Analysis Population Description

The ITT population included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether patients received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	439	439
Measure Type: Number; Unit of Measure: Participants
Complete response	2	3
Partial response	57	42
Stable/No response	136	136
Objective progression	191	206
Indeterminate	53	52

9. Secondary Outcome

Title	Duration of Response (DR) Based on Independent Radiologic Review.
Description	DR was defined as the time from first documentation of response assessed by independent review (CR or PR whichever occurred first) to date of progression or death due to any cause, whichever occurs first. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
Time Frame	From date of randomization until progression or death due to any cause. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Outcome Measure Data

Analysis Population Description

DR was analyzed for a subgroup of participants in the ITT population, who had an objective tumor response.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	52	35
Median (95% Confidence Interval); Unit of Measure: Months
	9.2; (6.9 to 20.2)	10.1; (5.6 to 14.8)

10. Secondary Outcome

Title	DR Based on Investigator Review.
Description	DR was defined as the time from first documentation of response assessed by investigator review (CR or PR whichever occurred first) to date of progression or death due to any cause, whichever occurs first. Per RECIST version 1.1: CR: disappearance of all pre-existing lesions except nodal disease, with all nodal lesions decreased to normal size (short axis<10 mm) and no appearance of new unequivocal malignant lesions; PR: >=30% decrease from baseline sum of diameters of all target lesions with no unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions; PD: >=20% increase in the sum of diameters of target lesions above the smallest sum observed, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
Time Frame	From date of randomization until progression or death due to any cause. Participants were followed up until progressive disease regardless of start of subsequent cancer therapy.

Outcome Measure Data

Analysis Population Description

DR was analyzed for a subgroup of participants in the ITT population, who had an objective tumor response.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	59	45
Median (95% Confidence Interval); Unit of Measure: Months
	10.4; (7.4 to 16.6)	9.2; (6.2 to 11.3)

11. Secondary Outcome

Title	Trough Concentrations (Ctrough) of Dacomitinib.
Description	Mean Ctrough values of dacomitinib observed from Cycle 2 through 5, Day 1 for dose compliant participants.
Time Frame	Baseline up to Cycle 5 Day 1

Outcome Measure Data

Analysis Population Description

Participants treated with dacomitinib with at least one measured plasma concentration.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	317
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Trough Plasma Concentration (ng/mL)
Cycle (C) 2 Day (D) 1 (n=317)	61.0102; (77%)
C3D1 (n=175)	46.5229; (97%)
C4D1 (n=131)	44.2708; (86%)
C5D1 (n=95)	38.0307; (83%)

12. Secondary Outcome

Title	Trough Concentrations (Ctrough) of PF-05199265.
Description	Mean Ctrough values of PF-05199265 observed from Cycle 2 through 5, Day 1 for dose compliant participants.
Time Frame	Baseline up to Cycle 5 Day 1

Outcome Measure Data

Analysis Population Description

Participants treated with dacomitinib with at least one measured plasma concentration.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	323
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Trough Plasma Concentration (ng/mL)
Cycle (C) 2 Day (D) 1 (n=323)	6.3695; (129%)
C3D1 (n=179)	5.8706; (123%)
C4D1 (n=136)	6.4380; (116%)
C5D1 (n=100)	6.5353; (118%)

13. Secondary Outcome

Title	Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough Patient Reported Disease Symptoms.
Description	TTD defined as the time from first dose (baseline) to the first time a patient's score in pain, dyspnea, fatigue or cough from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-LC13) increased by ≥10 points. A ≥10 point increase in score had to be maintained for ≥2 consecutive cycles for the symptom to be considered deteriorated. Participants were censored at the last time when they completed an assessment for pain, dyspnea, fatigue or cough if they had not deteriorated. A 10 point or higher change in the score is perceived by participants as clinically significant.
Time Frame	Data taken from Cycle 1 day 1 to the end of treatment or withdrawal.

Outcome Measure Data

Analysis Population Description

The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	421	424
Median (95% Confidence Interval); Unit of Measure: Months
	1.0; (1.0 to 1.9)	1.0; (0.9 to 1.4)

14. Secondary Outcome

Title	Mean and Difference in Mean in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Description	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Scores ranged from 0-100 where a higher score indicated a better level of quality of life. Overall scores present the mean score for that scale from all time-point data.
Time Frame	Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores.

Outcome Measure Data

Analysis Population Description

The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	421	424
Mean (95% Confidence Interval); Unit of Measure: Units on a scale.
QLQ-C30 Global QoL	56.4068; (54.631 to 58.183)	58.3425; (56.554 to 60.131)
QLQ-C30 Cognitive Functioning	83.8980; (82.275 to 85.521)	83.0913; (81.461 to 84.722)
QLQ-C30 Emotional Functioning	79.1982; (77.390 to 81.007)	78.4682; (76.658 to 80.279)
QLQ-C30 Physical Functioning	75.2138; (73.250 to 77.210)	73.6849; (71.719 to 75.651)
QLQ-C30 Role Functioning	69.3252; (66.771 to 71.879)	68.1033; (65.553 to 70.653)
QLQ-C30 Social Functioning	74.7868; (72.371 to 77.203)	76.2839; (73.864 to 78.703)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Global QoL. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-1.9357
	Confidence Interval	95%; -4.278 to 0.407
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 cognitive functioning. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	0.8067
	Confidence Interval	95%; -1.312 to 2.926
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 emotional functioning. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model
	Estimated Value	0.7300
	Confidence Interval	95%; -1.575 to 3.035
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 physical functioning. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	1.5289
	Confidence Interval	95%; -0.756 to 3.814
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 role functioning. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	1.2219
	Confidence Interval	95%; -1.975 to 4.419
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 social functioning. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-1.4970
	Confidence Interval	95%; -4.575 to 1.581
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

15. Secondary Outcome

Title	Mean and Difference in Mean in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30.
Description	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Scores ranged from 0-100 where a higher score indicated a greater degree of symptoms/problems. Overall scores present the mean score for that scale from all time-point data.
Time Frame	Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores.

Outcome Measure Data

Analysis Population Description

The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	421	424
Mean (95% Confidence Interval); Unit of Measure: Units on a scale.
QLQ-C30 Appetite loss	28.5960; (25.841 to 31.351)	27.3109; (24.532 to 30.090)
QLQ-C30 Constipation	8.2496; (6.392 to 10.108)	14.1726; (12.299 to 16.046)
QLQ-C30 Diarrhea	38.8641; (36.303 to 41.425)	18.6077; (16.017 to 21.198)
QLQ-C30 Dysponea	28.3313; (25.736 to 30.927)	32.8812; (30.282 to 35.480)
QLQ-C30 Fatigue	35.0885; (32.848 to 37.329)	36.7469; (34.494 to 38.999)
QLQ-C30 Financial Difficulties	20.0597; (17.760 to 22.360)	20.0597; (17.760 to 22.360)
QLQ-C30 Insomnia	19.7903; (17.413 to 22.168)	24.6615; (22.276 to 27.046)
QLQ-C30 Nausea and Vomiting	9.1438; (7.759 to 10.528)	9.6362; (8.208 to 11.065)
QLQ-C30 Pain	25.1850; (22.867 to 27.503)	24.8754; (22.551 to 27.200)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Appetite loss. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	1.2851
	Confidence Interval	(2-Sided) 95%; -2.416 to 4.986
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Constipation. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-5.9230
	Confidence Interval	(2-Sided) 95%; -8.432 to -3.414
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Diarrhea. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model
	Estimated Value	20.2564
	Confidence Interval	(2-Sided) 95%; 16.874 to 23.639
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Dysponea. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-4.5499
	Confidence Interval	(2-Sided) 95%; -7.719 to -1.381
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Fatigue. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-1.6584
	Confidence Interval	(2-Sided) 95%; -4.442 to 1.125
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Financial Difficulties. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-0.1469
	Confidence Interval	95%; -3.056 to 2.762
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Insomnia. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-4.8711
	Confidence Interval	(2-Sided) 95%; -7.998 to -1.745
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Nausea and Vomiting. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-0.4924
	Confidence Interval	(2-Sided) 95%; -2.485 to 1.500
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for QLQ-C30 Pain. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	0.3096
	Confidence Interval	(2-Sided) 95%; -2.646 to 3.265
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

16. Secondary Outcome

Title	Mean and Difference in Mean in Lung Cancer Symptom Scores as Assessed by the EORTC QLQ- LC13.
Description	The QLQ-LC13 included questions specific to the disease associated symptoms (dyspnea, cough, haemoptysis, and site specific pain), treatment-related symptoms (sore mouth, dysphagia, neuropathy, and alopecia), and analgesic use of lung cancer patients. Scores range from 0-100 and a higher score indicates greater degree of symptoms/problems. Overall scores present the mean score for that scale from all time-point data.
Time Frame	Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores.

Outcome Measure Data

Analysis Population Description

The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	421	424
Mean (95% Confidence Interval); Unit of Measure: Units on a scale.
QLQ-LC13 Trouble Swallowing	10.1934; (8.360 to 12.027)	7.5553; (5.711 to 9.400)
QLQ-LC13 Coughing	28.3790; (26.037 to 30.721)	32.6294; (30.272 to 34.986)
QLQ-LC13 Haemoptysis	3.4751; (2.118 to 4.832)	4.5515; (2.615 to 6.488)
QLQ-LC13 Sore Mouth	20.4054; (18.115 to 22.696)	11.0509; (8.731 to 13.371)
QLQ-LC13 Shortness of Breath	27.1651; (25.161 to 29.169)	28.3413; (26.346 to 30.337)
QLQ-LC13 Peripheral Neuropathy	19.4905; (17.222 to 21.759)	20.1284; (17.850 to 22.407)
QLQ-LC13 Alopecia	14.8327; (11.848 to 17.818)	16.1963; (13.220 to 19.173)
QLQ-LC13 Pain in Chest	16.4268; (14.335 to 18.518)	17.6430; (15.541 to 19.745)
QLQ-LC13 Pain in Arm or Shoulder	15.9840; (13.864 to 18.104)	17.1315; (14.989 to 19.274)
QLQ-LC13 Pain in other Parts	21.5437; (19.020 to 24.067)	22.6124; (20.060 to 25.165)
QLQ-LC13 Any Med for Pain	61.8437; (58.169 to 65.519)	61.8115; (58.038 to 65.585)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Trouble Swallowing as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	2.6381
	Confidence Interval	95%; 0.172 to 5.104
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Coughing as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-4.2504
	Confidence Interval	95%; -7.178 to -1.322
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Haemoptysis as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model
	Estimated Value	-1.0764
	Confidence Interval	95%; -3.997 to 1.845
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Sore Mouth as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	9.3545
	Confidence Interval	95%; 6.211 to 12.497
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Shortness of Breath as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-1.1762
	Confidence Interval	95%; -3.560 to 1.208
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Peripheral Neuropathy as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-0.6378
	Confidence Interval	95%; -3.684 to 2.408
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Alopecia as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-1.3637
	Confidence Interval	95%; -4.546 to 1.819
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Pain in Chest as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-1.2163
	Confidence Interval	95%; -3.885 to 1.452
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Pain in Arm or Shoulder as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-1.1475
	Confidence Interval	95%; -3.902 to 1.607
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Pain Other Parts as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-1.0687
	Confidence Interval	95%; -4.488 to 2.351
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for Any Med for Pain as Assessed by the EORTC-QLQ-LC13. Estimated change from baseline was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-LC13 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	0.0322
	Confidence Interval	95%; -4.847 to 4.911
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

17. Secondary Outcome

Title	Mean and Difference in Mean of the EuroQoL-5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) Score
Description	The EQ-5D is a validated and reliable self-report preference-based measure developed by the EuroQoL Group to assess health-related quality of life. It consists of the EQ-5D descriptive system and a visual analogue scale-the EQ VAS. The EQ-5D descriptive system measures a participants' health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting "no health problems," "moderate health problems," and "extreme health problems." The EQ VAS records the respondent's self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame	Data taken from Cycle 1 day 1 to the end of treatment or withdrawal, averaged (mean) to provide overall scores.

Outcome Measure Data

Analysis Population Description

The PRO analysis set included all participants who started treatment and completed the baseline and at least 1 post-dosing PRO assessment.

Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description:	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
Overall Number of Participants Analyzed	421	424
Mean (95% Confidence Interval); Unit of Measure: Units on a scale.
	65.1908; (63.519 to 66.863)	65.5794; (63.908 to 67.250)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo), Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Comments	Analysis presented for EQ-5D VAS. Mean difference was from a repeated measures mixed-effects model with an intercept term, treatment, treatment-by-time interaction, and baseline EORTC QLQ-C30 subscale baseline score (intercept and time from first dose are included as random effects). Confidence intervals provided were not adjusted for multiplicity.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Repeated measures mixed-effects model.
	Estimated Value	-0.3886
	Confidence Interval	95%; -2.413 to 1.636
	Estimation Comments	This analysis represents the mean difference between the dacomitinib arm (Arm A) and the erlotinib arm (Arm B).

Adverse Events

Time Frame	AE reporting period is from 1st dose of study drug through 28 days after last dose of study drug. SAE reporting period is from informed consent through 28 days after last dose of study drug. The longest duration of treatment in this study was 48 weeks.
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
Arm/Group Description	Participants randomized to Arm A received dacomitinib 45 mg orally once daily and erlotinib 150 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.	Participants randomized to Arm B received erlotinib 150 mg orally once daily and dacomitinib 45 mg placebo orally once daily. Participants began treatment within 3 days after randomization and continued treatment without breaks until they experienced unacceptable toxicity, tumor progression, or death.
All-Cause Mortality
	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	178/436 (40.83%)	169/436 (38.76%)
Blood and lymphatic system disorders
Anaemia * 1	3/436 (0.69%)	8/436 (1.83%)
Coagulopathy * 1	1/436 (0.23%)	0/436 (0.00%)
Febrile bone marrow aplasia * 1	0/436 (0.00%)	1/436 (0.23%)
Febrile neutropenia * 1	4/436 (0.92%)	2/436 (0.46%)
Splenic infarction * 1	0/436 (0.00%)	1/436 (0.23%)
Thrombocytopenia * 1	0/436 (0.00%)	2/436 (0.46%)
Cardiac disorders
Acute coronary syndrome * 1	0/436 (0.00%)	1/436 (0.23%)
Acute myocardial infarction * 1	1/436 (0.23%)	1/436 (0.23%)
Angina pectoris * 1	0/436 (0.00%)	1/436 (0.23%)
Atrial fibrillation * 1	2/436 (0.46%)	3/436 (0.69%)
Cardiac arrest * 1	1/436 (0.23%)	2/436 (0.46%)
Cardiac failure * 1	1/436 (0.23%)	1/436 (0.23%)
Cardiac tamponade * 1	1/436 (0.23%)	0/436 (0.00%)
Myocardial infarction * 1	2/436 (0.46%)	3/436 (0.69%)
Myocardial ischaemia * 1	1/436 (0.23%)	0/436 (0.00%)
Palpitations * 1	1/436 (0.23%)	1/436 (0.23%)
Pericardial effusion * 1	1/436 (0.23%)	1/436 (0.23%)
Supraventricular tachycardia * 1	1/436 (0.23%)	0/436 (0.00%)
Tachycardia * 1	0/436 (0.00%)	1/436 (0.23%)
Endocrine disorders
Hypothyroidism * 1	0/436 (0.00%)	1/436 (0.23%)
Eye disorders
Cataract * 1	0/436 (0.00%)	1/436 (0.23%)
Retinal artery embolism * 1	0/436 (0.00%)	1/436 (0.23%)
Retinal detachment * 1	0/436 (0.00%)	1/436 (0.23%)
Gastrointestinal disorders
Abdominal pain * 1	2/436 (0.46%)	1/436 (0.23%)
Abdominal pain upper * 1	1/436 (0.23%)	0/436 (0.00%)
Constipation * 1	1/436 (0.23%)	1/436 (0.23%)
Diarrhoea * 1	20/436 (4.59%)	7/436 (1.61%)
Diverticulum intestinal haemorrhagic * 1	1/436 (0.23%)	0/436 (0.00%)
Duodenal ulcer * 1	0/436 (0.00%)	1/436 (0.23%)
Dysphagia * 1	1/436 (0.23%)	2/436 (0.46%)
Gastric haemorrhage * 1	0/436 (0.00%)	1/436 (0.23%)
Gastric ulcer * 1	0/436 (0.00%)	1/436 (0.23%)
Gastric ulcer haemorrhage * 1	0/436 (0.00%)	1/436 (0.23%)
Gastrointestinal haemorrhage * 1	1/436 (0.23%)	0/436 (0.00%)
Haematemesis * 1	0/436 (0.00%)	1/436 (0.23%)
Inguinal hernia * 1	1/436 (0.23%)	0/436 (0.00%)
Intestinal obstruction * 1	0/436 (0.00%)	1/436 (0.23%)
Gastrointestinal disorder * 1	0/436 (0.00%)	1/436 (0.23%)
Melaena * 1	1/436 (0.23%)	1/436 (0.23%)
Nausea * 1	4/436 (0.92%)	4/436 (0.92%)
Oesophageal stenosis * 1	0/436 (0.00%)	1/436 (0.23%)
Pancreatitis * 1	0/436 (0.00%)	1/436 (0.23%)
Pancreatitis acute * 1	1/436 (0.23%)	1/436 (0.23%)
Pneumoperitoneum * 1	1/436 (0.23%)	1/436 (0.23%)
Rectal haemorrhage * 1	0/436 (0.00%)	1/436 (0.23%)
Retroperitoneal haemorrhage * 1	0/436 (0.00%)	1/436 (0.23%)
Stomatitis * 1	2/436 (0.46%)	1/436 (0.23%)
Upper gastrointestinal haemorrhage * 1	1/436 (0.23%)	0/436 (0.00%)
Vomiting * 1	5/436 (1.15%)	3/436 (0.69%)
General disorders
Asthenia * 1	3/436 (0.69%)	2/436 (0.46%)
Axillary pain * 1	0/436 (0.00%)	1/436 (0.23%)
Catheter site pain * 1	1/436 (0.23%)	1/436 (0.23%)
Chest pain * 1	0/436 (0.00%)	2/436 (0.46%)
Condition aggravated * 1	3/436 (0.69%)	2/436 (0.46%)
Death * 1	5/436 (1.15%)	1/436 (0.23%)
Disease progression * 1	53/436 (12.16%)	48/436 (11.01%)
Drug interaction * 1	0/436 (0.00%)	1/436 (0.23%)
Fatigue * 1	1/436 (0.23%)	4/436 (0.92%)
General physical health deterioration * 1	4/436 (0.92%)	10/436 (2.29%)
Mucosal inflammation * 1	1/436 (0.23%)	0/436 (0.00%)
Oedema peripheral * 1	3/436 (0.69%)	0/436 (0.00%)
Pain * 1	0/436 (0.00%)	2/436 (0.46%)
Performance status decreased * 1	1/436 (0.23%)	0/436 (0.00%)
Pyrexia * 1	5/436 (1.15%)	2/436 (0.46%)
Hepatobiliary disorders
Cholangitis acute * 1	1/436 (0.23%)	0/436 (0.00%)
Drug-induced liver injury * 1	0/436 (0.00%)	1/436 (0.23%)
Hepatic failure * 1	1/436 (0.23%)	0/436 (0.00%)
Hepatic function abnormal * 1	0/436 (0.00%)	1/436 (0.23%)
Hyperbilirubinaemia * 1	1/436 (0.23%)	0/436 (0.00%)
Infections and infestations
Abdominal sepsis * 1	0/436 (0.00%)	1/436 (0.23%)
Acne pustular * 1	1/436 (0.23%)	0/436 (0.00%)
Bronchitis * 1	0/436 (0.00%)	3/436 (0.69%)
Bronchopneumonia * 1	1/436 (0.23%)	0/436 (0.00%)
Cellulitis * 1	1/436 (0.23%)	1/436 (0.23%)
Diverticulitis * 1	0/436 (0.00%)	1/436 (0.23%)
Infectious pleural effusion * 1	1/436 (0.23%)	0/436 (0.00%)
Lobar pneumonia * 1	2/436 (0.46%)	0/436 (0.00%)
Lung abscess * 1	0/436 (0.00%)	1/436 (0.23%)
Lung infection * 1	1/436 (0.23%)	3/436 (0.69%)
Nasopharyngitis * 1	0/436 (0.00%)	1/436 (0.23%)
Oral candidiasis * 1	0/436 (0.00%)	1/436 (0.23%)
Pneumonia * 1	12/436 (2.75%)	15/436 (3.44%)
Pneumonia pseudomonal * 1	1/436 (0.23%)	0/436 (0.00%)
Pyelonephritis * 1	1/436 (0.23%)	0/436 (0.00%)
Rash pustular * 1	0/436 (0.00%)	1/436 (0.23%)
Respiratory tract infection * 1	2/436 (0.46%)	3/436 (0.69%)
Rhinitis * 1	0/436 (0.00%)	1/436 (0.23%)
Sepsis * 1	2/436 (0.46%)	3/436 (0.69%)
Septic shock * 1	0/436 (0.00%)	1/436 (0.23%)
Staphylococcal sepsis * 1	1/436 (0.23%)	0/436 (0.00%)
Viral infection * 1	1/436 (0.23%)	0/436 (0.00%)
Urinary tract infection * 1	2/436 (0.46%)	1/436 (0.23%)
Injury, poisoning and procedural complications
Fall * 1	1/436 (0.23%)	1/436 (0.23%)
Femoral neck fracture * 1	3/436 (0.69%)	0/436 (0.00%)
Femur fracture * 1	0/436 (0.00%)	1/436 (0.23%)
Incisional hernia * 1	1/436 (0.23%)	0/436 (0.00%)
Radiation oesophagitis * 1	0/436 (0.00%)	1/436 (0.23%)
Radius fracture * 1	1/436 (0.23%)	0/436 (0.00%)
Rib fracture * 1	1/436 (0.23%)	0/436 (0.00%)
Investigations
Alanine aminotransferase increased * 1	0/436 (0.00%)	1/436 (0.23%)
Aspartate aminotransferase increased * 1	0/436 (0.00%)	1/436 (0.23%)
Aspiration bronchial * 1	1/436 (0.23%)	0/436 (0.00%)
Blood calcium decreased * 1	1/436 (0.23%)	0/436 (0.00%)
Blood creatine phosphokinase increased * 1	1/436 (0.23%)	0/436 (0.00%)
Blood creatinine increased * 1	1/436 (0.23%)	0/436 (0.00%)
C-reactive protein increased * 1	1/436 (0.23%)	0/436 (0.00%)
Haemoglobin decreased * 1	0/436 (0.00%)	2/436 (0.46%)
Hepatic enzyme increased * 1	0/436 (0.00%)	1/436 (0.23%)
International normalised ratio increased * 1	1/436 (0.23%)	0/436 (0.00%)
Platelet count decreased * 1	0/436 (0.00%)	1/436 (0.23%)
Metabolism and nutrition disorders
Cachexia * 1	1/436 (0.23%)	0/436 (0.00%)
Decreased appetite * 1	2/436 (0.46%)	4/436 (0.92%)
Dehydration * 1	13/436 (2.98%)	6/436 (1.38%)
Diabetes mellitus * 1	0/436 (0.00%)	1/436 (0.23%)
Diabetes mellitus inadequate control * 1	1/436 (0.23%)	0/436 (0.00%)
Electrolyte imbalance * 1	0/436 (0.00%)	1/436 (0.23%)
Failure to thrive * 1	2/436 (0.46%)	0/436 (0.00%)
Hypercalcaemia * 1	2/436 (0.46%)	0/436 (0.00%)
Hyperglycaemia * 1	0/436 (0.00%)	1/436 (0.23%)
Malnutrition * 1	0/436 (0.00%)	1/436 (0.23%)
Musculoskeletal and connective tissue disorders
Back pain * 1	1/436 (0.23%)	0/436 (0.00%)
Chondrocalcinosis * 1	0/436 (0.00%)	1/436 (0.23%)
Muscle spasms * 1	1/436 (0.23%)	0/436 (0.00%)
Musculoskeletal pain * 1	1/436 (0.23%)	0/436 (0.00%)
Myalgia * 1	0/436 (0.00%)	1/436 (0.23%)
Pain in extremity * 1	0/436 (0.00%)	2/436 (0.46%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic * 1	1/436 (0.23%)	0/436 (0.00%)
Lung neoplasm malignant * 1	1/436 (0.23%)	2/436 (0.46%)
Lung squamous cell carcinoma metastatic * 1	1/436 (0.23%)	0/436 (0.00%)
Malignant neoplasm progression * 1	0/436 (0.00%)	1/436 (0.23%)
Malignant pleural effusion * 1	0/436 (0.00%)	1/436 (0.23%)
Metastases to central nervous system * 1	0/436 (0.00%)	1/436 (0.23%)
Metastases to liver * 1	1/436 (0.23%)	0/436 (0.00%)
Metastases to meninges * 1	0/436 (0.00%)	1/436 (0.23%)
Metastatic neoplasm * 1	1/436 (0.23%)	0/436 (0.00%)
Neoplasm progression * 1	0/436 (0.00%)	1/436 (0.23%)
Non-small cell lung cancer * 1	2/436 (0.46%)	1/436 (0.23%)
Squamous cell carcinoma of lung * 1	0/436 (0.00%)	1/436 (0.23%)
Tumour associated fever * 1	1/436 (0.23%)	0/436 (0.00%)
Tumour pain * 1	1/436 (0.23%)	0/436 (0.00%)
Nervous system disorders
Cerebral infarction * 1	0/436 (0.00%)	2/436 (0.46%)
Cerebral ischaemia * 1	1/436 (0.23%)	0/436 (0.00%)
Cerebrovascular accident * 1	0/436 (0.00%)	1/436 (0.23%)
Dizziness * 1	1/436 (0.23%)	1/436 (0.23%)
Hemiparesis * 1	1/436 (0.23%)	0/436 (0.00%)
Hypotonia * 1	1/436 (0.23%)	0/436 (0.00%)
Paraplegia * 1	0/436 (0.00%)	1/436 (0.23%)
Seizure * 1	1/436 (0.23%)	0/436 (0.00%)
Syncope * 1	0/436 (0.00%)	1/436 (0.23%)
Transient ischaemic attack * 1	1/436 (0.23%)	1/436 (0.23%)
Psychiatric disorders
Delirium * 1	1/436 (0.23%)	0/436 (0.00%)
Depression * 1	0/436 (0.00%)	1/436 (0.23%)
Mental status changes * 1	2/436 (0.46%)	0/436 (0.00%)
Renal and urinary disorders
Acute kidney injury * 1	4/436 (0.92%)	2/436 (0.46%)
Calculus ureteric * 1	1/436 (0.23%)	0/436 (0.00%)
Haematuria * 1	1/436 (0.23%)	0/436 (0.00%)
Prerenal failure * 1	1/436 (0.23%)	0/436 (0.00%)
Renal failure * 1	4/436 (0.92%)	2/436 (0.46%)
Renal impairment * 1	1/436 (0.23%)	2/436 (0.46%)
Urinary retention * 1	0/436 (0.00%)	1/436 (0.23%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome * 1	1/436 (0.23%)	1/436 (0.23%)
Acute respiratory failure * 1	3/436 (0.69%)	1/436 (0.23%)
Bronchitis chronic * 1	0/436 (0.00%)	1/436 (0.23%)
Chronic obstructive pulmonary disease * 1	1/436 (0.23%)	1/436 (0.23%)
Dyspnoea * 1	8/436 (1.83%)	8/436 (1.83%)
Haemoptysis * 1	5/436 (1.15%)	1/436 (0.23%)
Haemothorax * 1	0/436 (0.00%)	1/436 (0.23%)
Hypoxia * 1	2/436 (0.46%)	1/436 (0.23%)
Interstitial lung disease * 1	2/436 (0.46%)	3/436 (0.69%)
Pleural effusion * 1	2/436 (0.46%)	2/436 (0.46%)
Pneumonia aspiration * 1	2/436 (0.46%)	0/436 (0.00%)
Pneumonitis * 1	0/436 (0.00%)	1/436 (0.23%)
Pneumothorax * 1	3/436 (0.69%)	2/436 (0.46%)
Pulmonary alveolar haemorrhage * 1	0/436 (0.00%)	1/436 (0.23%)
Pulmonary embolism * 1	4/436 (0.92%)	3/436 (0.69%)
Pulmonary fibrosis * 1	1/436 (0.23%)	0/436 (0.00%)
Pulmonary haemorrhage * 1	0/436 (0.00%)	1/436 (0.23%)
Respiratory distress * 1	0/436 (0.00%)	1/436 (0.23%)
Respiratory failure * 1	4/436 (0.92%)	5/436 (1.15%)
Skin and subcutaneous tissue disorders
Dermatitis allergic * 1	1/436 (0.23%)	0/436 (0.00%)
Drug eruption * 1	1/436 (0.23%)	0/436 (0.00%)
Erythema multiforme * 1	1/436 (0.23%)	0/436 (0.00%)
Exfoliative rash * 1	0/436 (0.00%)	1/436 (0.23%)
Rash * 1	1/436 (0.23%)	2/436 (0.46%)
Rash generalised * 1	1/436 (0.23%)	0/436 (0.00%)
Rash maculo-papular * 1	0/436 (0.00%)	1/436 (0.23%)
Surgical and medical procedures
Hospitalisation * 1	0/436 (0.00%)	1/436 (0.23%)
Internal fixation of fracture * 1	1/436 (0.23%)	0/436 (0.00%)
Vascular disorders
Deep vein thrombosis * 1	0/436 (0.00%)	2/436 (0.46%)
Embolism * 1	1/436 (0.23%)	1/436 (0.23%)
Hypovolaemic shock * 1	1/436 (0.23%)	0/436 (0.00%)
Peripheral artery thrombosis * 1	1/436 (0.23%)	0/436 (0.00%)
Phlebitis * 1	1/436 (0.23%)	0/436 (0.00%)
Venous thrombosis * 1	0/436 (0.00%)	1/436 (0.23%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	2%
	Arm A (Blinded Dacomitinib and Blinded Erlotinib Placebo)	Arm B (Blinded Erlotinib and Blinded Dacomitinib Placebo)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	424/436 (97.25%)	417/436 (95.64%)
Blood and lymphatic system disorders
Anaemia * 1	35/436 (8.03%)	43/436 (9.86%)
Cardiac disorders
Tachycardia * 1	5/436 (1.15%)	10/436 (2.29%)
Eye disorders
Dry eye * 1	16/436 (3.67%)	5/436 (1.15%)
Gastrointestinal disorders
Abdominal pain * 1	21/436 (4.82%)	19/436 (4.36%)
Abdominal pain upper * 1	21/436 (4.82%)	20/436 (4.59%)
Cheilitis * 1	13/436 (2.98%)	8/436 (1.83%)
Constipation * 1	43/436 (9.86%)	59/436 (13.53%)
Diarrhoea * 1	322/436 (73.85%)	217/436 (49.77%)
Dry mouth * 1	14/436 (3.21%)	13/436 (2.98%)
Dyspepsia * 1	20/436 (4.59%)	16/436 (3.67%)
Dysphagia * 1	16/436 (3.67%)	16/436 (3.67%)
Gastrooesophageal reflux disease * 1	9/436 (2.06%)	11/436 (2.52%)
Nausea * 1	90/436 (20.64%)	81/436 (18.58%)
Stomatitis * 1	81/436 (18.58%)	52/436 (11.93%)
Vomiting * 1	71/436 (16.28%)	70/436 (16.06%)
General disorders
Asthenia * 1	65/436 (14.91%)	59/436 (13.53%)
Chest pain * 1	21/436 (4.82%)	36/436 (8.26%)
Fatigue * 1	78/436 (17.89%)	92/436 (21.10%)
General physical health deterioration * 1	9/436 (2.06%)	11/436 (2.52%)
Malaise * 1	9/436 (2.06%)	7/436 (1.61%)
Mucosal inflammation * 1	67/436 (15.37%)	28/436 (6.42%)
Oedema peripheral * 1	17/436 (3.90%)	29/436 (6.65%)
Pain * 1	12/436 (2.75%)	21/436 (4.82%)
Pyrexia * 1	41/436 (9.40%)	36/436 (8.26%)
Xerosis * 1	14/436 (3.21%)	7/436 (1.61%)
Infections and infestations
Conjunctivitis * 1	29/436 (6.65%)	14/436 (3.21%)
Cystitis * 1	9/436 (2.06%)	5/436 (1.15%)
Lower respiratory tract infection * 1	5/436 (1.15%)	9/436 (2.06%)
Nasopharyngitis * 1	19/436 (4.36%)	20/436 (4.59%)
Paronychia * 1	94/436 (21.56%)	44/436 (10.09%)
Rash pustular * 1	9/436 (2.06%)	9/436 (2.06%)
Respiratory tract infection * 1	10/436 (2.29%)	5/436 (1.15%)
Upper respiratory tract infection * 1	13/436 (2.98%)	12/436 (2.75%)
Urinary tract infection * 1	18/436 (4.13%)	19/436 (4.36%)
Injury, poisoning and procedural complications
Fall * 1	8/436 (1.83%)	10/436 (2.29%)
Investigations
Alanine aminotransferase increased * 1	8/436 (1.83%)	22/436 (5.05%)
Aspartate aminotransferase increased * 1	10/436 (2.29%)	21/436 (4.82%)
Blood bilirubin increased * 1	0/436 (0.00%)	11/436 (2.52%)
Blood creatinine increased * 1	17/436 (3.90%)	13/436 (2.98%)
Weight decreased * 1	64/436 (14.68%)	38/436 (8.72%)
Metabolism and nutrition disorders
Decreased appetite * 1	138/436 (31.65%)	119/436 (27.29%)
Dehydration * 1	26/436 (5.96%)	14/436 (3.21%)
Hypoalbuminaemia * 1	8/436 (1.83%)	16/436 (3.67%)
Hypokalaemia * 1	28/436 (6.42%)	21/436 (4.82%)
Hypomagnesaemia * 1	22/436 (5.05%)	19/436 (4.36%)
Hyponatraemia * 1	13/436 (2.98%)	13/436 (2.98%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	15/436 (3.44%)	10/436 (2.29%)
Back pain * 1	35/436 (8.03%)	30/436 (6.88%)
Muscle spasms * 1	15/436 (3.44%)	11/436 (2.52%)
Muscular weakness * 1	2/436 (0.46%)	9/436 (2.06%)
Musculoskeletal chest pain * 1	13/436 (2.98%)	8/436 (1.83%)
Musculoskeletal pain * 1	20/436 (4.59%)	19/436 (4.36%)
Myalgia * 1	2/436 (0.46%)	9/436 (2.06%)
Pain in extremity * 1	26/436 (5.96%)	26/436 (5.96%)
Nervous system disorders
Dizziness * 1	17/436 (3.90%)	25/436 (5.73%)
Dysgeusia * 1	34/436 (7.80%)	22/436 (5.05%)
Headache * 1	18/436 (4.13%)	20/436 (4.59%)
Psychiatric disorders
Anxiety * 1	16/436 (3.67%)	19/436 (4.36%)
Depression * 1	7/436 (1.61%)	9/436 (2.06%)
Insomnia * 1	14/436 (3.21%)	25/436 (5.73%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	54/436 (12.39%)	73/436 (16.74%)
Dysphonia * 1	8/436 (1.83%)	9/436 (2.06%)
Dyspnoea * 1	76/436 (17.43%)	81/436 (18.58%)
Dyspnoea exertional * 1	10/436 (2.29%)	9/436 (2.06%)
Epistaxis * 1	37/436 (8.49%)	23/436 (5.28%)
Haemoptysis * 1	23/436 (5.28%)	37/436 (8.49%)
Nasal inflammation * 1	9/436 (2.06%)	0/436 (0.00%)
Oropharyngeal pain * 1	9/436 (2.06%)	8/436 (1.83%)
Pleural effusion * 1	11/436 (2.52%)	5/436 (1.15%)
Productive cough * 1	13/436 (2.98%)	12/436 (2.75%)
Rhinorrhoea * 1	9/436 (2.06%)	7/436 (1.61%)
Skin and subcutaneous tissue disorders
Acne * 1	23/436 (5.28%)	19/436 (4.36%)
Alopecia * 1	14/436 (3.21%)	18/436 (4.13%)
Dermatitis acneiform * 1	81/436 (18.58%)	88/436 (20.18%)
Dry skin * 1	86/436 (19.72%)	84/436 (19.27%)
Erythema * 1	18/436 (4.13%)	21/436 (4.82%)
Palmar-plantar erythrodysaesthesia syndrome * 1	16/436 (3.67%)	7/436 (1.61%)
Pruritus * 1	49/436 (11.24%)	54/436 (12.39%)
Rash * 1	218/436 (50.00%)	203/436 (46.56%)
Rash maculo-papular * 1	18/436 (4.13%)	12/436 (2.75%)
Skin exfoliation * 1	15/436 (3.44%)	10/436 (2.29%)
Skin fissures * 1	24/436 (5.50%)	19/436 (4.36%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

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

Ramalingam SS, O'Byrne K, Boyer M, Mok T, Janne PA, Zhang H, Liang J, Taylor I, Sbar EI, Paz-Ares L. Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trials. Ann Oncol. 2016 Mar;27(3):423-9. doi: 10.1093/annonc/mdv593. Epub 2016 Jan 13. Erratum In: Ann Oncol. 2016 Jul;27(7):1363.

Ramalingam SS, Janne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. doi: 10.1016/S1470-2045(14)70452-8. Epub 2014 Oct 15.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01360554
• Other Study ID Numbers: A7471009; 2010-022656-22 ( EudraCT Number )
• First Submitted: April 12, 2011
• First Posted: May 25, 2011
• Results First Submitted: September 7, 2016
• Results First Posted: May 24, 2017
• Last Update Posted: May 24, 2017