ARCHER1050: A Study of Dacomitinib vs. Gefitinib in 1st-Line Treatment Of Advanced NSCLC.

• ClinicalTrials.gov Identifier: NCT01774721
• Recruitment Status: Completed
• First Posted: January 24, 2013
• Results First Posted: October 26, 2018
• Last Update Posted: November 14, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer With EGFR-Activating Mutations
• Interventions: Drug: Dacomitinib (PF-00299804); Drug: Gefitinib
• Enrollment: 452

Participant Flow

Recruitment Details
Pre-assignment Details	The study completed enrollment on 25 Mar 2015 with 452 participants randomized, 227 participants to the dacomitinib arm and 225 participants to the gefitinib arm. After the last data cutoff (DCO) date of 13 May 2019, 11 participants remained in the study to continue dacomitinib treatment. All 11 participants were discontinued from the study by last participant last visit (LPLV) on 27 Jan 2022.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Period Title: Overall Study
Started	227	225
Treated	227	224
Completed	0	0
Not Completed	227	225
Reason Not Completed
Death	133	152
Withdrawal by Subject	20	14
Lost to Follow-up	6	7
Did not meet eligibility criteria	0	3
Other reasons and patients who completed the 48-month follow-up period	58	49
Study terminated by sponsor	5	0
Disease progression	5	0

Baseline Characteristics

Arm/Group Title		Dacomitinib	Gefitinib	Total
Arm/Group Description		Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Total of all reporting groups
Overall Number of Baseline Participants		227	225	452
Baseline Analysis Population Description		ITT Population included all participants who were randomized, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or received a different treatment from that to which they were randomized.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	227 participants	225 participants	452 participants
		61.2 (11.26)	60.9 (10.17)	61.1 (10.72)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	227 participants	225 participants	452 participants
	Female	146 64.3%	125 55.6%	271 60.0%
	Male	81 35.7%	100 44.4%	181 40.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	227 participants	225 participants	452 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	227 100.0%	225 100.0%	452 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	227 participants	225 participants	452 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	170 74.9%	176 78.2%	346 76.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 0.4%	0 0.0%	1 0.2%
	White	56 24.7%	49 21.8%	105 23.2%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Based on Independent Radiologic Central (IRC) Review
Description	PFS: time from randomization to date of progression of disease (PD) as determined by IRC review as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD: >=20% increase in sum of diameters of target lesions (TLs), referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)

Outcome Measure Data

Analysis Population Description

Intent to treat (ITT) Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	225
Median (95% Confidence Interval); Unit of Measure: months
	14.7; (11.1 to 16.6)	9.2; (9.1 to 11.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	1-sided stratified log-rank test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.589
	Confidence Interval	(2-Sided) 95%; 0.469 to 0.739
	Estimation Comments	Based on stratified Cox regression model

2. 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 participant was known to be alive. OS (month)=[death date or last known alive date - randomization date + 1]/30.4375.
Time Frame	From randomization until death or last date known as alive, up to 45 months

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	225
Median (95% Confidence Interval); Unit of Measure: months
	34.1; (29.5 to 39.8)	27.0; (24.4 to 31.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0077
	Comments	[Not Specified]
	Method	1-sided stratified log-rank test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.748
	Confidence Interval	(2-Sided) 95%; 0.591 to 0.947
	Estimation Comments	Based on stratified Cox Regression model

3. Secondary Outcome

Title	OS at 30 Months (OS30m)
Description	OS30m was defined as the probability of a participant being alive at 30 months from date of randomization.
Time Frame	Up to 30 months from date of randomization

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	225
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: probability of survival
	56.4; (49.6 to 62.7)	45.7; (39.0 to 52.2)

4. Secondary Outcome

Title	Progression Free Survival (PFS) Based on Investigator Assessment
Description	PFS: time from randomization to date of PD as determined by investigator assessment as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause, whichever occurred first. PD for target lesions: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm; for non-target lesions: unequivocal progression of pre-existing lesions. Overall tumor burden increased sufficiently to merit discontinuation of therapy. In presence of stable disease (did not achieve partial response, complete response or PD) or partial response (>=30% decrease under baseline of sum of diameters of all target measurable lesions, short diameter used in the sum for target nodes, longest diameter used in sum for all other target lesions) in target disease; for new lesions: appearance of any new unequivocal malignant lesion indicated PD.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	225
Median (95% Confidence Interval); Unit of Measure: months
	16.6; (12.9 to 18.4)	11.0; (9.4 to 12.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	1-sided stratified log-rank test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.622
	Confidence Interval	(2-Sided) 95%; 0.497 to 0.779
	Estimation Comments	Based on stratified Cox regression model

5. Secondary Outcome

Title	Number of Participants With Best Overall Response (BOR) Based on IRC Review
Description	BOR for CR/PR:>=1 objective status (OBS) of CR/PR documented before PD; SD:>=1 OBS of stable documented >=8 weeks (wks) post treatment & before PD, not qualifying as CR/PR; PD:OBS of PD within 12 wks treatment, not qualifying as CR/PR/SD; indeterminate:PD not documented within 12 wks post treatment & no other response category applies. RECIST v1.1, CR:disappearance of all target lesions (TLs), non TLs;any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referring smallest sum diameters on study. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions;unequivocal progression of existing non TLs.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	225
Measure Type: Count of Participants; Unit of Measure: Participants
Complete response	12 5.3%	4 1.8%
Partial response	158 69.6%	157 69.8%
Stable disease	30 13.2%	27 12.0%
Progressive disease	12 5.3%	15 6.7%
Indeterminate	15 6.6%	22 9.8%

6. Secondary Outcome

Title	Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment
Description	BOR for CR/PR:>=1 objective status (OBS) of CR/PR documented before PD; SD:>=1 OBS of stable documented >=8 weeks (wks) post treatment & before PD, not qualifying as CR/PR; PD:OBS of PD within 12 wks treatment, not qualifying as CR/PR/SD; indeterminate:PD not documented within 12 wks post treatment & no other response category applies. RECIST v1.1, CR:disappearance of all target lesions (TLs), non TLs;any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referring smallest sum diameters on study. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions;unequivocal progression of existing non TLs.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	225
Measure Type: Count of Participants; Unit of Measure: Participants
Complete response	2 0.9%	1 0.4%
Partial response	169 74.4%	157 69.8%
Stable disease	38 16.7%	49 21.8%
Progressive disease	9 4.0%	11 4.9%
Indeterminate	9 4.0%	7 3.1%

7. Secondary Outcome

Title	Duration of Response (DoR)
Description	DoR was defined as time from first documentation of objective response(CR or PR, whichever occurred first)to date of PD/death from any cause, whichever occurred first. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs. DoR was recorded based on IRC review and investigator's assessment and summarized for subgroup of participants with objective disease response.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression or death due to any cause, whichever occurred first (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title		Dacomitinib	Gefitinib
Arm/Group Description:		Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed		227	225
Median (95% Confidence Interval); Unit of Measure: months
DoR: IRC review	Number Analyzed	170 participants	161 participants
		14.8; (12.0 to 17.4)	8.3; (7.4 to 9.2)
DoR: Investigator assessment	Number Analyzed	171 participants	158 participants
		15.9; (13.8 to 17.6)	9.2; (8.2 to 11.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	Comparison of dacomitinib vs gefitinib based on IRC review
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	1-sided stratified log-rank test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.403
	Confidence Interval	(2-Sided) 95%; 0.307 to 0.529
	Estimation Comments	Based on stratified Cox regression model

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	Comparison of dacomitinib vs gefitinib based on Investigator assessment
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	1-sided stratified log-rank test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.545
	Confidence Interval	(2-Sided) 95%; 0.418 to 0.711
	Estimation Comments	Based on stratified Cox regression model

8. Secondary Outcome

Title	Objective Response Rate (ORR) Based on IRC Review
Description	Percentage of participants with a BOR of either CR or PR based on IRC review recorded from the start of treatment until disease progression based on RECIST v1.1. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	225
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	74.9; (68.7 to 80.4)	71.6; (65.2 to 77.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1942
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

9. Secondary Outcome

Title	Objective Response Rate (ORR) Based on Investigator Assessment
Description	Percentage of participants with a BOR of either CR or PR based on investigator assessment recorded from the start of treatment until disease progression based on RECIST v1.1. CR: disappearance of all target lesions (TLs), non TLs; any pathological lymph nodes (LN) must reduce in short axis to <10 mm; normalization of tumour marker level, for non TL all LN must be non-pathological in size (<10 mm short axis); PR:>=30% decrease in sum of diameters of TLs, referring baseline sum diameters. PD:>=20% increase in sum of diameters of TLs, referring smallest sum on study, sum must be an absolute increase of >=5 mm, appearance of >=1 new lesions; unequivocal progression of existing non TLs.
Time Frame	Day 28 of Cycle 1, Cycle 2 then every 8 weeks until disease progression (up to 48 months)

Outcome Measure Data

Analysis Population Description

ITT Population included all randomized participants, with study treatment assignment designated according to initial randomization, regardless of whether participants received study treatment or a different treatment from that to which they were randomized.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	225
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	75.3; (69.2 to 80.8)	70.2; (63.8 to 76.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0924
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

10. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.AEs included both serious and non- serious adverse events. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between first dose of study drug and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame	From randomization until death or last date known as alive, up to 91 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Dacomitinib	Gefitinib	Dacomitinib (Ongoing at DCO)
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	DCO was the protocol-defined cutoff at 48 months from first dosing of the last enrolled participant (13 May 2019). At the DCO, 11 participants were ongoing in the dacomitinib arm and continued study treatment until disease progression, intolerable toxicities, withdrawal, death, or study terminated by sponsor, whichever occurred first. The 11 participants were analyzed for adverse events after LPLV on 27 Jan 2022.
Overall Number of Participants Analyzed	227	224	11
Measure Type: Count of Participants; Unit of Measure: Participants
TEAEs	226 99.6%	220 98.2%	11 100.0%
SAEs	69 30.4%	53 23.7%	4 36.4%

11. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI CTCAE Version 4.03: Biochemistry and Haematology
Description	Parameters included anaemia, activated partial thromboplastin time, haemoglobin, international normalized ratio, lymphocyte count, lymphopenia, neutrophils (absolute), platelets, prothrombin time and white blood cells. Biochemistry parameters included alanine aminotransferase (increased), alkaline phosphatase (increased), aspartate aminotransferase (increased), bilirubin (total), creatinine (increased), hypercalcaemia, hyperglycaemia, hyperkalaemia, hypermagnesaemia, hypernatraemia, hypoalbuminaemia, hypocalcaemia, hypoglycaemia, hypokalaemia, hypomagnesaemia, hyponatraemia. Test abnormalities were graded by AEs according to the Common Terminology Criteria for Adverse Events(NCI CTCAE) version 4.03 as Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening; Grade 5=death related to AE. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
Time Frame	From randomization until death or last date known as alive, up to 61 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	224
Measure Type: Count of Participants; Unit of Measure: Participants
Anaemia (Grade 3)	5 2.2%	6 2.7%
Haemoglobin increased(Grade 3)	0 0.0%	1 0.4%
Lymphopenia (Grade 3)	13 5.7%	6 2.7%
Neutrophil count (absolute) (Grade 3)	0 0.0%	2 0.9%
WBC count (Grade 3)	1 0.4%	1 0.4%
Alanine aminotransferase increased (Grade 3)	5 2.2%	26 11.6%
Alanine aminotransferase increased (Grade 4)	0 0.0%	3 1.3%
Aspartate aminotransferase increased (Grade 3)	2 0.9%	15 6.7%
Aspartate aminotransferase increased (Grade 4)	0 0.0%	3 1.3%
Alkaline phosphatase increased (Grade 3)	2 0.9%	5 2.2%
Bilirubin increased (total) (Grade 3)	1 0.4%	1 0.4%
Creatinine increased (Grade 3)	1 0.4%	1 0.4%
Hypercalcemia (Grade 3)	1 0.4%	0 0.0%
Hyperglycemia (Grade 3)	2 0.9%	5 2.2%
Hyperkalemia (Grade 3)	0 0.0%	1 0.4%
Hyperkalemia (Grade 4)	0 0.0%	2 0.9%
Hypermagnesemia (Grade 3)	9 4.0%	7 3.1%
Hypocalcemia (Grade 3)	3 1.3%	4 1.8%
Hypoglycemia (Grade 3)	0 0.0%	2 0.9%
Hypoglycemia (Grade 4)	1 0.4%	0 0.0%
Hypokalemia (Grade 3)	13 5.7%	5 2.2%
Hypokalemia (Grade 4)	2 0.9%	0 0.0%
Hypomagnesemia (Grade 3)	2 0.9%	0 0.0%
Hyponatremia (Grade 3)	5 2.2%	4 1.8%
Hyponatremia (Grade 4)	1 0.4%	1 0.4%

12. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities: Urinalysis
Description	Urinalysis parameter included urine protein, urine blood/haemoglobin, urine glucose and urine sediment. Test abnormalities was defined as deviation from normal range (higher or lower). Normal range of 24-hour urine protein test: less than 150 mg of protein per day, urine glucose: 0 to 0.8 mmol/L (millimole per liter), urine protein: 0 to 20 mg/dL (milligrams per deciliter). Urine blood/haemoglobin abnormality was defined as presence and absence of blood/haemoglobin in urine of participants. Urine sediment abnormality was defined as the presence of any bacteria, casts, crystals, and epithelial cells. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
Time Frame	From randomization until death or last date known as alive, up to 61 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	227	224
Measure Type: Count of Participants; Unit of Measure: Participants
High Urine Protein	1 0.4%	1 0.4%
Low Urine Glucose	1 0.4%	0 0.0%
High Urine Blood/Haemoglobin	4 1.8%	4 1.8%

13. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Vital Signs
Description	Criteria for vital signs abnormalities: postbaseline pulse rate less than (<) 50 beats per minute (bpm) or greater than (>)130 bpm and maximum increase from baseline in pulse rate >=30 bpm and maximum decrease from baseline in pulse rate <=30 bpm. Systolic blood pressure (BP) of maximum increase from baseline (MIB) >=40 millimeters of mercury (mmHg), maximum decrease from baseline (MDB) in systolic blood pressure =<60 mmHg. Diastolic blood pressure of MIB >=20 mmHg and MDB in diastolic blood pressure >-40 and =<-20 mm Hg. And MDB in diastolic BP<=-40 mmHg. Only categories with at least 1 participant with abnormality are reported in this outcome measure.
Time Frame	From randomization until death or last date known as alive, up to 61 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title		Dacomitinib	Gefitinib
Arm/Group Description:		Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed		227	224
Measure Type: Count of Participants; Unit of Measure: Participants
MIB in systolic BP >=40 mmHg	Number Analyzed	224 participants	223 participants
		16 7.1%	22 9.9%
MDB in systolic BP <=-60 mmHg	Number Analyzed	224 participants	223 participants
		0 0.0%	1 0.4%
MIB in diastolic BP >=20 mmHg	Number Analyzed	224 participants	223 participants
		42 18.8%	44 19.7%
MDB in diastolic BP >-40 and <=-20mmHg	Number Analyzed	224 participants	223 participants
		51 22.8%	53 23.8%
MDB in diastolic BP <=-40 mmHg	Number Analyzed	224 participants	223 participants
		0 0.0%	1 0.4%
Maximum post baseline pulse rate >130 bpm	Number Analyzed	226 participants	223 participants
		2 0.9%	2 0.9%
Minimum post baseline pulse rate <50 bpm	Number Analyzed	226 participants	223 participants
		3 1.3%	0 0.0%
MIB in pulse rate >=30 bpm	Number Analyzed	225 participants	223 participants
		16 7.1%	12 5.4%
MDB in pulse rate <=-30 bpm	Number Analyzed	225 participants	223 participants
		17 7.6%	15 6.7%
MIB in body weight >=10%	Number Analyzed	225 participants	223 participants
		28 12.4%	42 18.8%
MDB in body weight <=-10%	Number Analyzed	225 participants	223 participants
		46 20.4%	32 14.3%

14. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormality in Electrocardiogram (ECG)
Description	ECG parameters included corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). ECG criteria for abnormality: absolute value 450 - <480 msec, 480 - <500 msec, >=500msec. The number of participants with potentially clinically significant ECG findings at any visit were reported.
Time Frame	From randomization until death or last date known as alive, up to 61 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received. Here, "N" (number of participants analyzed) signifies participants who were evaluable for this specified outcome measure.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	217	7
Measure Type: Count of Participants; Unit of Measure: Participants
QTcF Criteria: 450-<480	5 2.3%	0 0.0%
QTcB Criteria: 450-<480	22 10.1%	0 0.0%
QTcB Criteria: 480-<500	3 1.4%	0 0.0%

15. Secondary Outcome

Title	Number of Participants With Maximum Relative Decrease From Baseline >20% in Left Ventricular Ejection Fraction (LVEF)
Description	An ejection fraction (EF) was the volumetric fraction of blood ejected from a ventricle of the heart with each heartbeat; it was a measure of the pumping efficiency of the heart. The EF of the left heart, known as the left ventricular ejection fraction, was a measure of the efficiency of pumping into the body's systemic circulation.
Time Frame	From baseline up to 7 days of Cycle 4 (up to 91 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received. Here "N" signifies number of participants who were evaluable for this specified outcome measure.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	191	199
Measure Type: Count of Participants; Unit of Measure: Participants
	5 2.6%	5 2.5%

16. Secondary Outcome

Title	Health Related Quality of Life (HRQOL): Time to Deterioration (TTD) in Pain, Dyspnea, Fatigue or Cough
Description	HRQOL was measured by standardized questionnaires (European Organization for Research and Treatment of Cancer (EORTC)) quality of life questionnaires (OLQ-C30) and its lung cancer module (QLQ-LC13). TTD in pain (chest, arm/shoulder), dyspnea, fatigue or cough was defined as time between baseline and first occurrence of increase in score of 10 points or greater from baseline in any of these 4 symptoms for at least two consecutive cycles. For those who had not shown deterioration, the data was censored at the last date when the participants completed an assessment for pain, dyspnea, fatigue or cough.
Time Frame	Baseline until the end of treatment (up to 48 months)

Outcome Measure Data

Analysis Population Description

Patient reported outcomes (PRO) analysis set included all enrolled participants, who started treatment and completed a baseline PRO assessments and at least one post-baseline PRO assessment after the first dose.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	226	222
Median (95% Confidence Interval); Unit of Measure: months
	3.8; (2.3 to 4.8)	6.6; (3.8 to 9.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dacomitinib, Gefitinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1641
	Comments	[Not Specified]
	Method	Unstratified Log-rank Test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	1.173
	Confidence Interval	(2-Sided) 95%; 0.928 to 1.483
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Overall Mean Scores of Euro Quality of Life-5 Dimension Visual Analog Scale (EQ-5D VAS)
Description	The Euro Quality of Life-5 dimension (EQ-5D) is a brief self-administered, validated reliable generic health status instrument. EQ-5D general health status can also be measured by a visual analog scale (EQ-5D VAS). EQ-5D VAS measures the participant's self-rated health status on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame	From Cycle 1 Day 1 up to 48 months

Outcome Measure Data

Analysis Population Description

PRO analysis set included all enrolled participants, who started treatment and completed a baseline PRO assessments and at least one post-baseline PRO assessment after the first dose. Here "N" signifies number of participants who were evaluable for this specified outcome measure.

Arm/Group Title	Dacomitinib	Gefitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	224	221
Mean (95% Confidence Interval); Unit of Measure: units on a scale
	73.3869; (71.608 to 75.166)	77.6923; (75.895 to 79.490)

18. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Dacomitinib and Its Metabolite PF-05199265
Description	Cmax was defined as maximum observed plasma concentration and can be observed directly from data.
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: nanogram per milliliter (ng/mL)
Dacomitinib	84.19 (21.90)
PF-05199265	12.77 (7.58)

19. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Dacomitinib and Its Metabolite PF-05199265
Description	Tmax was defined as time to first occurrence of Cmax and can be observed directly from data as time of first occurrence.
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose (sample collection time points had window of +/- 10% of nominal time) on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	19
Median (Full Range); Unit of Measure: hour
Dacomitinib	4.03; (2.0 to 24.0)
PF-05199265	6.0; (0.0 to 25.0)

20. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero (0) to End of Dosing Interval (AUCtau) of Dacomitinib and Its Metabolite PF-05199265
Description	AUCtau was defined as area under the plasma concentration-time curve over dosing interval tau and was determined by Linear/Log trapezoidal method.
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: nanogram*hour/milliliter (ng*hr/mL)
Dacomitinib	1712.08 (413.61)
PF-05199265	278.47 (163.53)

21. Secondary Outcome

Title	Averaged Plasma Concentration at Steady State (Cavg) of Dacomitinib and Its Metabolite PF-05199265
Description	Cavg was defined as averaged plasma concentration at steady state, and was calculated as AUCtau/tau.
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: ng/mL
Dacomitinib	71.33 (17.23)
PF-05199265	11.60 (6.81)

22. Secondary Outcome

Title	Minimum Observed Plasma Concentration (Cmin) of Dacomitinib and Its Metabolite PF-05199265
Description	Cmin was defined as minimum observed plasma concentration and can be observed directly from data.
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: ng/mL
Dacomitinib	60.64 (14.85)
PF-05199265	10.49 (6.26)

23. Secondary Outcome

Title	Fluctuation Coefficient Between Trough and Peak Plasma Concentration (DF) of Dacomitinib and Its Metabolite PF-05199265
Description	Fluctuation coefficient between trough and peak plasma concentration was determined as Cmax-Ctrough divided by Cavg, where Cmax was the maximum observed concentration within the dosing interval, Ctrough was the observed concentration prior to dose administration and Cavg was averaged plasma concentration at steady state.
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: Fluctuation coefficient
Dacomitinib	0.2883 (0.1460)
PF-05199265	0.1105 (0.0827)

24. Secondary Outcome

Title	Apparent Clearance (CL) of Dacomitinib
Description	Drug clearance was a quantitative measure of the rate at which a drug substance was removed from the blood (rate at which a drug is metabolized or eliminated by normal biological processes).
Time Frame	Pre-dose and 2, 4, 6, 8, and 24 hours post-dose on Cycle 2 Day 1 (Day 29)

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least 1 measured plasma concentration and were dose-compliant (who received 45 mg dacomitinib daily without interruptions/dose reductions for at least 14 days prior to day of data collection). This outcome measure was planned to be analyzed in Chinese subgroup only.

Arm/Group Title	Dacomitinib
Arm/Group Description:	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed	19
Mean (Standard Deviation); Unit of Measure: Liter/hour
	27.61 (5.97)

25. Secondary Outcome

Title	Pre-dose Plasma Concentrations (Ctrough) of Dacomitinib and Its Metabolite PF-05199265
Description	Trough plasma concentration was defined as the measured concentration at the end of a dosing interval at steady state (taken directly before next administration).
Time Frame	Pre-dose on Day 1 of Cycle 2, 3, 4, 5 and 6

Outcome Measure Data

Analysis Population Description

PK analysis set included all participants who were treated with dacomitinib with at least one measured plasma concentration and were dose-compliant. Dose-compliant participants were those who received 45 mg dacomitinib daily without interruptions or dose reductions for at least 14 days prior to the day of data collection. Here, 'Number Analyzed' = participants evaluable for this outcome measure at specified time points.

Arm/Group Title		Dacomitinib
Arm/Group Description:		Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.
Overall Number of Participants Analyzed		188
Mean (Standard Deviation); Unit of Measure: ng/mL
Cycle 2 Day 1: Dacomitinib	Number Analyzed	176 participants
		70.24 (27.16)
Cycle 3 Day 1: Dacomitinib	Number Analyzed	143 participants
		68.34 (25.80)
Cycle 4 Day 1: Dacomitinib	Number Analyzed	112 participants
		68.16 (25.49)
Cycle 5 Day 1: Dacomitinib	Number Analyzed	85 participants
		64.50 (25.52)
Cycle 6 Day 1: Dacomitinib	Number Analyzed	74 participants
		61.68 (22.58)
Cycle 2 Day 1: PF-05199265	Number Analyzed	176 participants
		13.20 (8.55)
Cycle 3 Day 1: PF-05199265	Number Analyzed	143 participants
		14.42 (9.10)
Cycle 4 Day 1: PF-05199265	Number Analyzed	112 participants
		13.70 (8.33)
Cycle 5 Day 1: PF-05199265	Number Analyzed	85 participants
		12.48 (6.69)
Cycle 6 Day 1: PF-05199265	Number Analyzed	74 participants
		13.05 (6.52)

Adverse Events

Time Frame	From randomization until death or last date known as alive, up to 91 months
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Safety analysis set included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.
Arm/Group Title	Dacomitinib	Gefitinib	Dacomitinib (Ongoing at DCO)
Arm/Group Description	Participants received 45 mg of dacomitinib tablets orally once daily in each treatment cycle of 28 days, up to a maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	Participants received 250 mg of gefitinib tablets orally once daily in each treatment cycle of 28 days, for maximum of 48 months until disease progression, intolerable toxicities, withdrawal, death, or investigator decision dictated by protocol compliance, whichever occurred first.	DCO was the protocol-defined cutoff at 48 months from first dosing of the last enrolled participant (13 May 2019). At the DCO, 11 participants were ongoing in the dacomitinib arm and continued study treatment until disease progression, intolerable toxicities, withdrawal, death, or study terminated by sponsor, whichever occurred first. The 11 participants were analyzed for adverse events after LPLV on 27 Jan 2022.
All-Cause Mortality
	Dacomitinib	Gefitinib	Dacomitinib (Ongoing at DCO)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	133/227 (58.59%)	152/224 (67.86%)	1/11 (9.09%)
Serious Adverse Events
	Dacomitinib	Gefitinib	Dacomitinib (Ongoing at DCO)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	69/227 (30.40%)	53/224 (23.66%)	4/11 (36.36%)
Blood and lymphatic system disorders
Leukocytosis * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Anaemia * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Cardiac disorders
Cardiac tamponade * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Arteriosclerosis coronary artery * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Eye disorders
Keratitis * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Cataract * 1	1/227 (0.44%)	0/224 (0.00%)	1/11 (9.09%)
Gastrointestinal disorders
Diarrhoea * 1	5/227 (2.20%)	0/224 (0.00%)	1/11 (9.09%)
Abdominal pain * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Abdominal distension * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Gastric ulcer haemorrhage * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Ileus * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Mouth haemorrhage * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Rectal haemorrhage * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Stomatitis * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Vomiting * 1	1/227 (0.44%)	1/224 (0.45%)	0/11 (0.00%)
Dyspepsia * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Haematochezia * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Large intestinal obstruction * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Nausea * 1	1/227 (0.44%)	1/224 (0.45%)	0/11 (0.00%)
General disorders
Disease progression * 1	9/227 (3.96%)	12/224 (5.36%)	0/11 (0.00%)
Death * 1	1/227 (0.44%)	1/224 (0.45%)	0/11 (0.00%)
Multiple organ dysfunction syndrome * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Non-cardiac chest pain * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Pyrexia * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
General physical health deterioration * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Hepatobiliary disorders
Liver injury * 1	2/227 (0.88%)	1/224 (0.45%)	0/11 (0.00%)
Drug-induced liver injury * 1	1/227 (0.44%)	1/224 (0.45%)	0/11 (0.00%)
Bile duct stone * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Cholecystitis acute * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Cholangitis * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Infections and infestations
Pneumonia * 1	5/227 (2.20%)	2/224 (0.89%)	0/11 (0.00%)
Respiratory tract infection * 1	2/227 (0.88%)	1/224 (0.45%)	0/11 (0.00%)
Urinary tract infection * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Bronchitis * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Bronchopulmonary aspergillosis * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Diverticulitis * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Escherichia urinary tract infection * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Gastroenteritis * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Infection * 2	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Lung infection * 1	1/227 (0.44%)	1/224 (0.45%)	0/11 (0.00%)
Upper respiratory tract infection * 1	1/227 (0.44%)	0/224 (0.00%)	1/11 (9.09%)
Herpes zoster * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Arthritis bacterial * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Otitis media chronic * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Injury, poisoning and procedural complications
Facial bones fracture * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Hip fracture * 1	1/227 (0.44%)	1/224 (0.45%)	0/11 (0.00%)
Overdose * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Spinal fracture * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Extradural haematoma * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Subdural haematoma * 1	0/227 (0.00%)	2/224 (0.89%)	0/11 (0.00%)
Tibia fracture * 1	1/227 (0.44%)	1/224 (0.45%)	1/11 (9.09%)
Ligament injury * 1	1/227 (0.44%)	0/224 (0.00%)	1/11 (9.09%)
Ligament rupture * 1	1/227 (0.44%)	0/224 (0.00%)	1/11 (9.09%)
Concussion * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Investigations
Alanine aminotransferase increased * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Aspartate aminotransferase increased * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Hepatic enzyme increased * 1	0/227 (0.00%)	2/224 (0.89%)	0/11 (0.00%)
Metabolism and nutrition disorders
Decreased appetite * 1	3/227 (1.32%)	0/224 (0.00%)	0/11 (0.00%)
Dehydration * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Malnutrition * 1	1/227 (0.44%)	1/224 (0.45%)	0/11 (0.00%)
Hyponatraemia * 1	0/227 (0.00%)	2/224 (0.89%)	0/11 (0.00%)
Musculoskeletal and connective tissue disorders
Bone pain * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Muscular weakness * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Musculoskeletal pain * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Back pain * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Polymyalgia rheumatica * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Chronic myeloid leukaemia * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Malignant neoplasm progression * 1	0/227 (0.00%)	2/224 (0.89%)	0/11 (0.00%)
Pancreatic carcinoma * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Metastases to meninges * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Cancer pain * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Nervous system disorders
Cerebral infarction * 1	1/227 (0.44%)	3/224 (1.34%)	0/11 (0.00%)
Cerebral venous thrombosis * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Spinal cord compression * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Cerebrovascular accident * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Cognitive disorder * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Dizziness * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Post herpetic neuralgia * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Nervous system disorder * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Psychiatric disorders
Depression * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Suicide attempt * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Renal and urinary disorders
Acute kidney injury * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Ureterolithiasis * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion * 1	5/227 (2.20%)	2/224 (0.89%)	0/11 (0.00%)
Haemoptysis * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Pneumonitis * 1	2/227 (0.88%)	1/224 (0.45%)	0/11 (0.00%)
Pneumothorax * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Respiratory failure * 1	2/227 (0.88%)	0/224 (0.00%)	0/11 (0.00%)
Dyspnoea * 1	1/227 (0.44%)	4/224 (1.79%)	0/11 (0.00%)
Interstitial lung disease * 1	1/227 (0.44%)	1/224 (0.45%)	0/11 (0.00%)
Pulmonary embolism * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Bronchospasm * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Organising pneumonia * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Drug eruption * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Rash maculo-papular * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
Decubitus ulcer * 1	0/227 (0.00%)	1/224 (0.45%)	0/11 (0.00%)
Vascular disorders
Deep vein thrombosis * 1	1/227 (0.44%)	0/224 (0.00%)	0/11 (0.00%)
1 Term from vocabulary, MedDRA 24.1; 2 Term from vocabulary, 19.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Dacomitinib	Gefitinib	Dacomitinib (Ongoing at DCO)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	224/227 (98.68%)	217/224 (96.88%)	11/11 (100.00%)
Blood and lymphatic system disorders
Anaemia * 1	27/227 (11.89%)	18/224 (8.04%)	5/11 (45.45%)
Leukocytosis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Leukopenia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Cardiac disorders
Sinus tachycardia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Ear and labyrinth disorders
Deafness * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Eye disorders
Dry eye * 1	12/227 (5.29%)	8/224 (3.57%)	3/11 (27.27%)
Cataract * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Corneal erosion * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Eye pruritus * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Keratitis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Periorbital oedema * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Trichiasis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Gastrointestinal disorders
Diarrhoea * 1	199/227 (87.67%)	125/224 (55.80%)	10/11 (90.91%)
Stomatitis * 1	99/227 (43.61%)	41/224 (18.30%)	6/11 (54.55%)
Nausea * 1	45/227 (19.82%)	50/224 (22.32%)	3/11 (27.27%)
Constipation * 1	32/227 (14.10%)	29/224 (12.95%)	2/11 (18.18%)
Mouth ulceration * 1	32/227 (14.10%)	14/224 (6.25%)	3/11 (27.27%)
Vomiting * 1	22/227 (9.69%)	29/224 (12.95%)	0/11 (0.00%)
Aphthous ulcer * 1	13/227 (5.73%)	6/224 (2.68%)	0/11 (0.00%)
Oral pain * 1	13/227 (5.73%)	1/224 (0.45%)	4/11 (36.36%)
Abdominal pain * 1	14/227 (6.17%)	13/224 (5.80%)	0/11 (0.00%)
Dysphagia * 1	10/227 (4.41%)	12/224 (5.36%)	1/11 (9.09%)
Abdominal pain upper * 1	10/227 (4.41%)	14/224 (6.25%)	0/11 (0.00%)
Angular cheilitis * 1	12/227 (5.29%)	2/224 (0.89%)	0/11 (0.00%)
Dry mouth * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Toothache * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Abdominal pain lower * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Chapped lips * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Glossodynia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
General disorders
Asthenia * 1	32/227 (14.10%)	30/224 (13.39%)	1/11 (9.09%)
Chest pain * 1	19/227 (8.37%)	27/224 (12.05%)	3/11 (27.27%)
Fatigue * 1	26/227 (11.45%)	20/224 (8.93%)	1/11 (9.09%)
Mucosal inflammation * 1	21/227 (9.25%)	8/224 (3.57%)	0/11 (0.00%)
Pyrexia * 1	22/227 (9.69%)	18/224 (8.04%)	3/11 (27.27%)
Oedema peripheral * 1	13/227 (5.73%)	7/224 (3.13%)	0/11 (0.00%)
Pain * 1	16/227 (7.05%)	14/224 (6.25%)	3/11 (27.27%)
Mass * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Hepatobiliary disorders
Hepatic function abnormal * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Cholelithiasis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Immune system disorders
Immune system disorder * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Infections and infestations
Paronychia * 1	140/227 (61.67%)	45/224 (20.09%)	9/11 (81.82%)
Conjunctivitis * 1	46/227 (20.26%)	10/224 (4.46%)	3/11 (27.27%)
Upper respiratory tract infection * 1	36/227 (15.86%)	29/224 (12.95%)	5/11 (45.45%)
Nasopharyngitis * 1	26/227 (11.45%)	20/224 (8.93%)	3/11 (27.27%)
Rash pustular * 1	15/227 (6.61%)	3/224 (1.34%)	2/11 (18.18%)
Urinary tract infection * 1	14/227 (6.17%)	8/224 (3.57%)	0/11 (0.00%)
Folliculitis * 1	12/227 (5.29%)	4/224 (1.79%)	1/11 (9.09%)
Bronchitis * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Nasal vestibulitis * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Gingivitis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Otitis externa * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Pharyngotonsillitis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Rhinitis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Skin infection * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Injury, poisoning and procedural complications
Contusion * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Fall * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Skin abrasion * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Investigations
Weight decreased * 1	67/227 (29.52%)	43/224 (19.20%)	5/11 (45.45%)
Alanine aminotransferase increased * 1	53/227 (23.35%)	90/224 (40.18%)	7/11 (63.64%)
Aspartate aminotransferase increased * 1	49/227 (21.59%)	84/224 (37.50%)	5/11 (45.45%)
Blood bilirubin increased * 1	19/227 (8.37%)	20/224 (8.93%)	1/11 (9.09%)
Blood alkaline phosphatase increased * 1	16/227 (7.05%)	8/224 (3.57%)	2/11 (18.18%)
Gamma-glutamyltransferase increased * 1	17/227 (7.49%)	19/224 (8.48%)	3/11 (27.27%)
White blood cell count decreased * 1	6/227 (2.64%)	14/224 (6.25%)	1/11 (9.09%)
Weight increased * 1	11/227 (4.85%)	19/224 (8.48%)	3/11 (27.27%)
Haemoglobin decreased * 1	14/227 (6.17%)	5/224 (2.23%)	0/11 (0.00%)
Blood lactate dehydrogenase increased * 1	8/227 (3.52%)	12/224 (5.36%)	1/11 (9.09%)
Blood creatinine increased * 1	0/227 (0.00%)	0/224 (0.00%)	3/11 (27.27%)
Blood albumin decreased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Blood glucose increased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Blood potassium decreased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Blood uric acid increased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Eosinophil count increased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Glomerular filtration rate decreased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Neutrophil count decreased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Neutrophil count increased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Platelet count decreased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Platelet count increased * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Metabolism and nutrition disorders
Decreased appetite * 1	73/227 (32.16%)	58/224 (25.89%)	2/11 (18.18%)
Hypokalaemia * 1	25/227 (11.01%)	13/224 (5.80%)	2/11 (18.18%)
Hypoalbuminaemia * 1	12/227 (5.29%)	10/224 (4.46%)	1/11 (9.09%)
Hyponatraemia * 1	12/227 (5.29%)	8/224 (3.57%)	0/11 (0.00%)
Hyperuricaemia * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Hyperlipidaemia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Hypernatraemia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Tetany * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Hypocalcaemia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Musculoskeletal and connective tissue disorders
Pain in extremity * 1	34/227 (14.98%)	26/224 (11.61%)	5/11 (45.45%)
Musculoskeletal pain * 1	26/227 (11.45%)	31/224 (13.84%)	2/11 (18.18%)
Back pain * 1	26/227 (11.45%)	37/224 (16.52%)	3/11 (27.27%)
Arthralgia * 1	19/227 (8.37%)	14/224 (6.25%)	2/11 (18.18%)
Myalgia * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Periarthritis * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Intervertebral disc protrusion * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Joint swelling * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Musculoskeletal chest pain * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Nervous system disorders
Dysgeusia * 1	15/227 (6.61%)	11/224 (4.91%)	0/11 (0.00%)
Paraesthesia * 1	15/227 (6.61%)	11/224 (4.91%)	1/11 (9.09%)
Headache * 1	17/227 (7.49%)	21/224 (9.38%)	1/11 (9.09%)
Dizziness * 1	12/227 (5.29%)	17/224 (7.59%)	2/11 (18.18%)
Hypoaesthesia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Sciatica * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Vertebral artery stenosis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Psychiatric disorders
Insomnia * 1	32/227 (14.10%)	33/224 (14.73%)	1/11 (9.09%)
Anxiety * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Depression * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Renal and urinary disorders
Nephrolithiasis * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Reproductive system and breast disorders
Pelvic fluid collection * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Vulvovaginal rash * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	47/227 (20.70%)	46/224 (20.54%)	5/11 (45.45%)
Dyspnoea * 1	31/227 (13.66%)	29/224 (12.95%)	1/11 (9.09%)
Epistaxis * 1	22/227 (9.69%)	5/224 (2.23%)	3/11 (27.27%)
Nasal inflammation * 1	15/227 (6.61%)	3/224 (1.34%)	0/11 (0.00%)
Haemoptysis * 1	10/227 (4.41%)	13/224 (5.80%)	0/11 (0.00%)
Productive cough * 1	10/227 (4.41%)	12/224 (5.36%)	1/11 (9.09%)
Oropharyngeal pain * 1	0/227 (0.00%)	0/224 (0.00%)	3/11 (27.27%)
Nasal mucosal ulcer * 1	0/227 (0.00%)	0/224 (0.00%)	2/11 (18.18%)
Catarrh * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Dysphonia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Laryngeal pain * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Nasal mucosal disorder * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform * 1	112/227 (49.34%)	64/224 (28.57%)	3/11 (27.27%)
Dry skin * 1	64/227 (28.19%)	39/224 (17.41%)	0/11 (0.00%)
Alopecia * 1	53/227 (23.35%)	29/224 (12.95%)	4/11 (36.36%)
Pruritus * 1	47/227 (20.70%)	33/224 (14.73%)	3/11 (27.27%)
Rash * 1	41/227 (18.06%)	26/224 (11.61%)	2/11 (18.18%)
Palmar-plantar erythrodysaesthesia syndrome * 1	33/227 (14.54%)	7/224 (3.13%)	2/11 (18.18%)
Rash maculo-papular * 1	29/227 (12.78%)	27/224 (12.05%)	4/11 (36.36%)
Dermatitis * 1	25/227 (11.01%)	9/224 (4.02%)	1/11 (9.09%)
Skin fissures * 1	21/227 (9.25%)	7/224 (3.13%)	1/11 (9.09%)
Acne * 1	19/227 (8.37%)	13/224 (5.80%)	0/11 (0.00%)
Erythema * 1	14/227 (6.17%)	3/224 (1.34%)	1/11 (9.09%)
Drug eruption * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Eczema * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Hirsutism * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Nail disorder * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Pain of skin * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Papule * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Skin ulcer * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
Vascular disorders
Hypertension * 1	19/227 (8.37%)	21/224 (9.38%)	2/11 (18.18%)
Ischaemia * 1	0/227 (0.00%)	0/224 (0.00%)	1/11 (9.09%)
1 Term from vocabulary, MedDRA 24.1; * Indicates events were collected by non-systematic assessment

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.

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

Results Point of Contact

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

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

Li J, Nickens D, Wilner K, Tan W. Evaluation of the Effect of Proton Pump Inhibitors on the Efficacy of Dacomitinib and Gefitinib in Patients with Advanced Non-Small Cell Lung Cancer and EGFR-Activating Mutations. Oncol Ther. 2021 Dec;9(2):525-539. doi: 10.1007/s40487-021-00156-2. Epub 2021 Jun 13.

Cheng Y, Mok TS, Zhou X, Lu S, Zhou Q, Zhou J, Du Y, Yu P, Liu X, Hu C, Lu Y, Zhang Y, Lee KH, Nakagawa K, Linke R, Wong CH, Tang Y, Zhu F, Wilner KD, Wu YL. Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050). Lung Cancer. 2021 Apr;154:176-185. doi: 10.1016/j.lungcan.2021.02.025. Epub 2021 Feb 23.

Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. doi: 10.1007/s40265-020-01441-6.

Corral J, Mok TS, Nakagawa K, Rosell R, Lee KH, Migliorino MR, Pluzanski A, Linke R, Devgan G, Tan W, Quinn S, Wang T, Wu YL. Effects of dose modifications on the safety and efficacy of dacomitinib for EGFR mutation-positive non-small-cell lung cancer. Future Oncol. 2019 Aug;15(24):2795-2805. doi: 10.2217/fon-2019-0299. Epub 2019 Jul 17.

Nagano T, Tachihara M, Nishimura Y. Dacomitinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) to treat non-small cell lung cancer. Drugs Today (Barc). 2019 Apr;55(4):231-236. doi: 10.1358/dot.2019.55.4.2965337.

Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. doi: 10.1200/JCO.2018.78.7994. Epub 2018 Jun 4. Erratum In: J Clin Oncol. 2020 Nov 1;38(31):3725.

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• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01774721
• Other Study ID Numbers: A7471050; DP312804 ( Other Identifier: Pfizer )
• First Submitted: January 21, 2013
• First Posted: January 24, 2013
• Results First Submitted: March 29, 2018
• Results First Posted: October 26, 2018
• Last Update Posted: November 14, 2023