A Randomized Trial Of PF-00299804 Taken Orally Versus Erlotinib Taken Orally For Treatment Of Advanced Non-Small Cell Lung Cancer That Has Progressed After One Or Two Prior Chemotherapy Regimen

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00769067
• Collaborator: (none)
• Enrollment: 188
• Locations: 59
• Arms: 2
• Duration (Months): 69
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will compare PF-00299804 given orally on continuous schedule to the approved drug, erlotinib, in patients whose non-small cell lung cancer has progressed after chemotherapy; patients will be randomized to receive one of these drugs, and followed for efficacy and tolerance of each.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Erlotinib; Drug: PF-00299804	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 188 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase 2 Trial Of Pf-00299804 Versus Erlotinib For The Treatment Of Advanced Non-small Cell Lung Cancer After Failure Of At Least One Prior Chemotherapy Regimen
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A	Drug: Erlotinib; Continuous oral dosing at 150 mg daily.
Experimental: B	Drug: PF-00299804; Continuous oral dosing at 45mg daily

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks]

   PFS: Time in weeks from randomization to date of objective disease progression or death due to any cause, whichever occurred first. PFS was calculated as (first event date or last known event-free date [if the event date unavailable] minus the date of randomization plus 1) divided by 7. Objective progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LDs) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

Secondary Outcome Measures

1. Categorical Summary of Overall Scale Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [Baseline up to Cycle 44 (Week 188)]

   EORTC QLQ-C30: included global health status/quality of life (QoL), functional (Fn) scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Scores were averaged, transformed to 0-100 scale; higher score for Global Qol/Fn scales=better level of QoL/functioning or higher score for symptom scales/items=greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline: for Global QoL/Fn scales >=10; for symptom scale/item <=-10), Worsened (if average scales change from baseline: for Global QoL/Fn scales <=-10; for symptom scale/item >=10), and Stable (if average scales change from baseline >-10 but <10 for Global QoL/Fn scales and symptom scale/item) and participants in each category are reported.

2. Categorical Summary of Overall Scale Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) [Baseline up to Cycle 44 (Week 188)]

   QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Scores averaged, transformed to 0-100 scale; higher symptom score = greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline <=-10), Worsened (if average scales change from baseline >=10), and Stable (if average scales change from baseline >-10 but <10) and participants in each category are reported.

3. Dermatology Life Quality Index (DLQI) [Cycle (C) 1 Day (D) 1 (baseline), C1D10-14, D1 of subsequent cycles up to C44]

   DLQI: 10-item questionnaire to measure how much the participant's skin problem has impacted their life over the previous week on following 6 domains: symptoms/feelings (2 questions), daily activities (2 questions), leisure (2 questions), work/school (1 question), personal relationships (2 questions), and treatment (1 question). All questions were answered on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much/prevented work or studying). The DLQI total evaluable score was calculated by summing the score of each question and ranged from 0 to 30, where higher scores indicated more quality of life impairment.

4. Percentage of Participants With Objective Response [Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks]

   Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of the LDs of target lesion, taking as reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.

5. Best Overall Response (BOR) [Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks]

   Number of participants with BOR according to RECIST version 1.0: CR= disappearance of all target and non-target lesions. PR= at least 30% decrease in sum of LDs of target lesion, taking as reference baseline sum LD. Stable/no response= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LDs since treatment started. Objective progression= at least a 20% increase in sum of LDs of target lesions, taking as reference the smallest sum of LDs recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

6. Duration of Response (DR) [Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks]

   Time in weeks from first documentation of objective tumor response to objective tumor progression or symptomatic deterioration or death due to any cause, whichever occurred first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or symptomatic deterioration or death due to any cause or last known progression-free date [if none of the event dates available] minus the date of the first CR or PR [which ever occurred first] that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.

7. Overall Survival (OS) [Baseline until end of treatment (15 August 2014); followed up every 8 weeks after discontinuation from study treatment.]

   Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7.

Other Outcome Measures

1. Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation [Baseline]

   Tumor tissue were analyzed at a sponsor-designated laboratory to investigate KRAS and EGFR status (wild type or mutated). Participants who did not provide samples for central laboratory analysis confirmation were classified as "unknown". Additionally blood specimens were analyzed at a sponsor-designated laboratory for T790M mutation in EGFR.

2. Soluble Protein Biomarkers Level [Cycle (C) 1 Day (D) 1 (baseline), D1 of each subsequent cycle up to end of treatment (up to 121 weeks)]

   Blood specimens were analyzed at a sponsor-designated laboratory for analysis of shed proteins/receptors related to Human Epidermal Growth Factor Receptor (HER) signaling (EGFR, HER-2, Epithelial-cadherin [E-cadherin]). The data collection after C12D1 was not performed, as there were too few participants across both treatment arms after C12D1.

3. Trough Plasma Concentration (Ctrough) of Dacomitinib (PF-00299804) [C1D10-14, C2D1, C3D1, C4D1]

   Only participants from "Dacomitinib" treatment arm were planned to be analyzed for this outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• advanced measurable Non-Small Cell Lung Cancer (NSCLC);

• progressed after 1-2 prior chemotherapy;

• Eastern Cooperative Oncology Group (ECOG) 0-2;

• tissue available for future KRAS/ EGFR testing

Exclusion Criteria:

• prior Epidermal Growth Factor Receptor (EGFR) targeted therapy;

• active or untreated Central Nervous System (CNS) metastases;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwest Alabama Cancer Center	Muscle Shoals	Alabama	United States	35661
2	Agajanian Institute of Oncology and Hematology	Montebello	California	United States	90640
3	Bridgeport Hospital	Bridgeport	Connecticut	United States	06610
4	Wittingham Cancer Center @ Norwalk Hospital	Norwalk	Connecticut	United States	06856
5	Medical Oncology & Hematology, P.C.	Waterbury	Connecticut	United States	06708
6	Winship Cancer Institute at Grady Health Systems	Atlanta	Georgia	United States	30303
7	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322-1013
8	Winship Cancer Institute at Emory University	Atlanta	Georgia	United States	30322
9	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
10	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
11	Augusta Oncology Associates, P.C.	Augusta	Georgia	United States	30901
12	Augusta Oncology Associates, PC	Augusta	Georgia	United States	30909
13	John B. Amos Cancer Center	Columbus	Georgia	United States	31904
14	Georgia Cancer Specialists	Decatur	Georgia	United States	30033
15	The Longstreet Cancer Center	Gainesville	Georgia	United States	30501
16	Central Georgia Cancer Care, P.C.	Macon	Georgia	United States	31201
17	Northwest Georgia Oncology Center	Marietta	Georgia	United States	30106
18	Central Georgia Cancer Care, P.C.	Warner Robins	Georgia	United States	31088-2259
19	Kootenai Cancer Center at Post Falls	Post Falls	Idaho	United States	83854
20	Kootenai Cancer Center	Post Falls	Idaho	United States	83854
21	Midwestern Regional Medical Center	Zion	Illinois	United States	60099
22	Center for Blood and Cancer Disorders	Bethesda	Maryland	United States	20817
23	Associates in Oncology/Hematology, PC	Rockville	Maryland	United States	20850
24	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
25	The West Clinic	Memphis	Tennessee	United States	38120
26	Oncology/Hematology Associates	Clarksburg	West Virginia	United States	26301
27	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
28	St. Vincent's Hospital	Fitzroy	Victoria	Australia	3065
29	The Andrew Love Cancer Centre,	Geelong	Victoria	Australia	3220
30	Border Medical Oncology	Wodonga	Victoria	Australia	3690
31	Irmandade da Santa Casa de Misericordia de Porto Alegre (ISCMPA) - Hospital Santa Rita	Porto Alegre	RS	Brazil	90050-170
32	Hospital Sao Lucas da PUCRS	Porto Alegre	RS	Brazil	90610-000
33	FUNDACAO PIO XII Hospital de Cancer de Barretos	Barretos	SP	Brazil	14784-400
34	Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira - ICESP	Sao Paulo	SP	Brazil	01246-000
35	BC Cancer Agency - Vancouver Centre	Vancouver	British Columbia	Canada	V5Z 4E6
36	Royal Victoria Hospital	Barrie	Ontario	Canada	L4M 6M2
37	RSM Durham Regional Cancer Centre - Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
38	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
39	Department of Clinical Oncology	Shatin	New Territories	Hong Kong
40	Department of Clinical Oncology, Tuen Mun Hospital	Tuen Mun	New Territories	Hong Kong
41	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
42	Severance Hospital, Yonsei University College of Medicine, Yonsei Cancer Center	Seoul		Korea, Republic of	120-752
43	SamsungMedicalCenter,SungkyunkwanUnivSchoolofMedicine,Div. of Hematology-Oncology, Dep. of Medicine	Seoul		Korea, Republic of	135-710
44	Medex spolka cywilna	Chrzanow		Poland	32-500
45	¿KardioDent¿	Krakow		Poland	30-045
46	"Vesalius" Sp. z o.o.	Krakow		Poland	31-108
47	Zaklad Rentgena i USG Wyrobek spolka jawna	Krakow		Poland	31-215
48	Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie	Warsaw		Poland	02-781
49	Niepubliczny Zaklad Opieki Zdrowotnej AVI Centrum Medyczne	Warszawa		Poland	00-728
50	Ponce School of Medicine / CAIMED Center	Ponce		Puerto Rico	00716
51	National Cancer Centre	Singapore		Singapore	169610
52	Hospital Universitari Germans Trias I Pujol	Badalona	Barcelona	Spain	08916
53	Hospital Son Llatzer	Palma de Mallorca	Islas Baleares	Spain	07198
54	Hospital de Cruces	Barakaldo	Vizcaya	Spain	48903
55	Hospital Teresa Herrera	La Coruña		Spain	15006
56	National Taiwan University Hospital	Taipei		Taiwan	100
57	Taipei Veterans General Hospital, Chest Department	Taipei		Taiwan	112
58	Christie Hospital NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
59	Churchill Hospital	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00769067
• Other Study ID Numbers: A7471028; 2008-005235-14
• First Posted: Oct 8, 2008
• Last Update Posted: Oct 7, 2015
• Last Verified: Sep 1, 2015

• Keywords provided by Pfizer: Lung cancer; advanced; second or third line
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Period Title: Overall Study
STARTED	94	94
Treated	94	93
COMPLETED	0	0
NOT COMPLETED	94	94

Baseline Characteristics

Arm/Group Title	Erlotinib	Dacomitinib	Total
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Total of all reporting groups
Overall Participants	94	94	188
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.1 (12.0)	59.9 (9.5)	60.0 (10.8)
Sex: Female, Male (Count of Participants)
Female	38 40.4%	39 41.5%	77 41%
Male	56 59.6%	55 58.5%	111 59%

Outcome Measures

1. Secondary Outcome

Title	Categorical Summary of Overall Scale Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Description	EORTC QLQ-C30: included global health status/quality of life (QoL), functional (Fn) scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Scores were averaged, transformed to 0-100 scale; higher score for Global Qol/Fn scales=better level of QoL/functioning or higher score for symptom scales/items=greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline: for Global QoL/Fn scales >=10; for symptom scale/item <=-10), Worsened (if average scales change from baseline: for Global QoL/Fn scales <=-10; for symptom scale/item >=10), and Stable (if average scales change from baseline >-10 but <10 for Global QoL/Fn scales and symptom scale/item) and participants in each category are reported.
Time Frame	Baseline up to Cycle 44 (Week 188)

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants with study drug assignment designated according to initial randomization, regardless of treatment received. "N" (number of participants analyzed): participants who completed at least 1 item at baseline. "n": participants evaluable for specified category for each arm, respectively.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	88	90
Global QoL: Improved (n= 85, 85)	14 14.9%	11 11.7%
Global QoL: Worsened (n= 85, 85)	36 38.3%	34 36.2%
Global QoL: Stable (n= 85, 85)	35 37.2%	40 42.6%
Physical Functioning: Improved (n= 86, 88)	12 12.8%	14 14.9%
Physical Functioning: Worsened (n= 86, 88)	25 26.6%	24 25.5%
Physical Functioning: Stable (n= 86, 88)	49 52.1%	50 53.2%
Role Functioning: Improved (n= 86, 88)	18 19.1%	22 23.4%
Role Functioning: Worsened (n= 86, 88)	38 40.4%	31 33%
Role Functioning: Stable (n= 86, 88)	30 31.9%	35 37.2%
Cognitive Functioning: Improved (n= 86, 85)	13 13.8%	15 16%
Cognitive Functioning: Worsened (n= 86, 85)	21 22.3%	21 22.3%
Cognitive Functioning: Stable (n= 86, 85)	52 55.3%	49 52.1%
Emotional Functioning: Improved (n= 86, 85)	11 11.7%	21 22.3%
Emotional Functioning: Worsened (n= 86, 85)	27 28.7%	26 27.7%
Emotional Functioning: Stable (n= 86, 85)	48 51.1%	38 40.4%
Social Functioning: Improved (n= 86, 85)	24 25.5%	30 31.9%
Social Functioning: Worsened (n= 86, 85)	30 31.9%	19 20.2%
Social Functioning: Stable (n= 86, 85)	32 34%	36 38.3%
Fatigue: Improved (n= 86, 87)	18 19.1%	21 22.3%
Fatigue: Worsened (n= 86, 87)	38 40.4%	35 37.2%
Fatigue: Stable (n= 86, 87)	30 31.9%	31 33%
Pain: Improved (n= 86, 87)	19 20.2%	19 20.2%
Pain: Worsened (n= 86, 87)	30 31.9%	34 36.2%
Pain: Stable (n= 86, 87)	37 39.4%	34 36.2%
Nausea and Vomiting: Improved (n= 86, 87)	13 13.8%	13 13.8%
Nausea and Vomiting: Worsened (n= 86, 87)	27 28.7%	26 27.7%
Nausea and Vomiting: Stable (n= 86, 87)	46 48.9%	48 51.1%
Dyspnea: Improved (n= 86, 88)	23 24.5%	25 26.6%
Dyspnea: Worsened (n= 86, 88)	26 27.7%	25 26.6%
Dyspnea: Stable (n= 86, 88)	37 39.4%	38 40.4%
Loss of Appetite: Improved (n= 85, 87)	17 18.1%	19 20.2%
Loss of Appetite: Worsened (n= 85, 87)	41 43.6%	43 45.7%
Loss of Appetite: Stable (n= 85, 87)	27 28.7%	25 26.6%
Insomnia: Improved (n= 86, 87)	23 24.5%	22 23.4%
Insomnia: Worsened (n= 86, 87)	32 34%	33 35.1%
Insomnia: Stable (n= 86, 87)	31 33%	32 34%
Constipation: Improved (n= 86, 85)	25 26.6%	32 34%
Constipation: Worsened (n= 86, 85)	16 17%	13 13.8%
Constipation: Stable (n= 86, 85)	45 47.9%	40 42.6%
Diarrhea: Improved (n= 86, 85)	6 6.4%	4 4.3%
Diarrhea: Worsened (n= 86, 85)	52 55.3%	67 71.3%
Diarrhea: Stable (n= 86, 85)	28 29.8%	14 14.9%
Financial Difficulties: Improved (n= 85, 85)	18 19.1%	17 18.1%
Financial Difficulties: Worsened (n= 85, 85)	21 22.3%	17 18.1%
Financial Difficulties: Stable (n= 85, 85)	46 48.9%	51 54.3%

2. Secondary Outcome

Title	Categorical Summary of Overall Scale Change in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module (EORTC QLQ-LC13)
Description	QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Scores averaged, transformed to 0-100 scale; higher symptom score = greater degree of symptoms. Overall scale change is categorized as Improved (if average scales change from baseline <=-10), Worsened (if average scales change from baseline >=10), and Stable (if average scales change from baseline >-10 but <10) and participants in each category are reported.
Time Frame	Baseline up to Cycle 44 (Week 188)

Outcome Measure Data

Analysis Population Description

ITT population: all randomized participants with study drug assignment designated according to initial randomization, regardless of treatment received. "N" (number of participants analyzed): participants who completed at least 1 item at baseline. "n": participants evaluable for specified category for each arm, respectively.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	88	89
Dyspnoea: Improved (n= 85, 87)	18 19.1%	24 25.5%
Dyspnoea: Worsened (n= 85, 87)	29 30.9%	20 21.3%
Dyspnoea: Stable (n= 85, 87)	38 40.4%	43 45.7%
Coughing: Improved (n= 85, 87)	24 25.5%	37 39.4%
Coughing: Worsened (n= 85, 87)	20 21.3%	20 21.3%
Coughing: Stable (n= 85, 87)	41 43.6%	30 31.9%
Haemoptysis: Improved (n= 85, 86)	5 5.3%	8 8.5%
Haemoptysis: Worsened (n= 85, 86)	10 10.6%	10 10.6%
Haemoptysis: Stable (n= 85, 86)	70 74.5%	68 72.3%
Sore mouth: Improved (n= 85, 87)	3 3.2%	5 5.3%
Sore mouth: Worsened (n= 85, 87)	38 40.4%	58 61.7%
Sore mouth: Stable (n= 85, 87)	44 46.8%	24 25.5%
Dysphagia: Improved (n= 85, 87)	7 7.4%	6 6.4%
Dysphagia: Worsened (n= 85, 87)	24 25.5%	35 37.2%
Dysphagia: Stable (n= 85, 87)	54 57.4%	46 48.9%
Peripheral: Improved (n= 85, 87)	22 23.4%	27 28.7%
Peripheral: Worsened (n= 85, 87)	23 24.5%	20 21.3%
Peripheral: Stable (n= 85, 87)	40 42.6%	40 42.6%
Alopecia: Improved (n= 84, 87)	20 21.3%	21 22.3%
Alopecia: Worsened (n= 84, 87)	13 13.8%	21 22.3%
Alopecia: Stable (n= 84, 87)	51 54.3%	45 47.9%
Pain in chest: Improved (n= 85, 87)	26 27.7%	30 31.9%
Pain in chest: Worsened (n= 85, 87)	21 22.3%	13 13.8%
Pain in chest: Stable (n= 85, 87)	38 40.4%	44 46.8%
Pain in arm or Shoulder: Improved (n= 85, 87)	19 20.2%	28 29.8%
Pain in arm or Shoulder: Worsened (n= 85, 87)	27 28.7%	17 18.1%
Pain in arm or Shoulder: Stable (n= 85, 87)	39 41.5%	42 44.7%
Pain in other parts: Improved (n= 83, 86)	26 27.7%	23 24.5%
Pain in other parts: Worsened (n= 83, 86)	27 28.7%	28 29.8%
Pain in other parts: Stable (n= 83, 86)	30 31.9%	35 37.2%

3. Secondary Outcome

Title	Dermatology Life Quality Index (DLQI)
Description	DLQI: 10-item questionnaire to measure how much the participant's skin problem has impacted their life over the previous week on following 6 domains: symptoms/feelings (2 questions), daily activities (2 questions), leisure (2 questions), work/school (1 question), personal relationships (2 questions), and treatment (1 question). All questions were answered on a 4-point Likert scale ranging from 0 (not at all/not relevant) to 3 (very much/prevented work or studying). The DLQI total evaluable score was calculated by summing the score of each question and ranged from 0 to 30, where higher scores indicated more quality of life impairment.
Time Frame	Cycle (C) 1 Day (D) 1 (baseline), C1D10-14, D1 of subsequent cycles up to C44

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants with study drug assignment designated according to initial randomization, regardless of treatment received. Here "N" (number of participants analyzed) signifies participants evaluable for this measure; "n" signifies participants evaluable for specified category for each arm, respectively.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	87	91
C1D1 (n= 87, 91)	0.70 (1.97)	0.88 (2.38)
C1D10-14 (n=68, 81)	4.35 (6.25)	3.06 (4.94)
C2D1 (n= 80, 82)	5.16 (6.29)	3.91 (4.07)
C3D1 (n= 63, 63)	4.08 (5.67)	5.52 (6.65)
C4D1 (n= 39, 43)	3.97 (4.59)	5.95 (6.38)
C5D1 (n= 25, 38)	3.56 (3.61)	5.37 (6.08)
C6D1 (n= 16, 27)	4.13 (4.80)	5.37 (6.67)
C7D1 (n= 13, 27)	4.38 (4.07)	4.93 (6.54)
C8D1 (n= 11, 24)	4.64 (3.14)	5.33 (6.23)
C9D1 (n= 11, 19)	3.82 (3.34)	4.84 (5.76)
C10D1 (n= 11, 17)	3.36 (3.04)	5.88 (7.37)
C11D1 (n= 10, 15)	5.60 (5.13)	6.73 (7.57)
C12D1 (n= 7, 14)	6.71 (5.62)	5.50 (6.99)
C13D1 (n= 7, 13)	5.57 (4.08)	5.08 (7.90)
C14D1 (n= 6, 12)	6.00 (3.95)	6.00 (7.35)
C15D1 (n= 6, 12)	4.67 (3.78)	5.92 (7.40)
C16D1 (n= 5, 11)	5.40 (3.91)	5.36 (8.18)
C17D1 (n= 4, 11)	5.00 (4.24)	5.55 (7.85)
C18D1 (n= 4, 10)	3.00 (2.16)	7.30 (9.08)
C19D1 (n= 4, 9)	4.50 (2.38)	7.22 (7.73)
C20D1 (n= 2, 10)	3.50 (3.54)	6.50 (8.57)
C21D1 (n= 2, 9)	3.50 (2.12)	7.33 (7.76)
C22D1 (n= 1, 7)	1.00 (NA)	2.14 (3.67)
C23D1 (n= 1, 7)	1.00 (NA)	3.71 (3.99)
C24D1 (n= 1, 7)	3.00 (NA)	2.57 (4.08)
C25D1 (n= 1, 6)	8.00 (NA)	2.83 (4.45)
C26D1 (n= 0, 6)	NA (NA)	2.67 (4.13)
C27D1 (n= 0, 6)	NA (NA)	3.33 (3.98)
C28D1 (n= 0, 6)	NA (NA)	3.17 (3.82)
C29D1 (n= 0, 6)	NA (NA)	5.33 (4.59)
C30D1 (n= 0, 5)	NA (NA)	4.20 (5.12)
C31D1 (n= 0, 5)	NA (NA)	4.20 (4.97)
C32D1 (n= 0, 4)	NA (NA)	2.75 (2.50)
C33D1 (n= 0, 4)	NA (NA)	3.00 (2.94)
C34D1 (n= 0, 2)	NA (NA)	4.00 (1.41)
C35D1 (n= 0, 2)	NA (NA)	12.50 (13.44)
C36D1 (n= 0, 2)	NA (NA)	1.50 (2.12)
C37D1 (n= 0, 2)	NA (NA)	1.50 (2.12)
C38D1 (n= 0, 2)	NA (NA)	0.50 (0.71)
C39D1 (n= 0, 2)	NA (NA)	0.00 (0.00)
C40D1 (n= 0, 2)	NA (NA)	0.50 (0.71)
C41D1 (n= 0, 2)	NA (NA)	0.00 (0.00)
C42D1 (n= 0, 2)	NA (NA)	0.50 (0.71)
C43D1 (n= 0, 1)	NA (NA)	3.00 (NA)
C44D1 (n= 0, 0)	NA (NA)	NA (NA)

4. Other Pre-specified Outcome

Title	Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation
Description	Tumor tissue were analyzed at a sponsor-designated laboratory to investigate KRAS and EGFR status (wild type or mutated). Participants who did not provide samples for central laboratory analysis confirmation were classified as "unknown". Additionally blood specimens were analyzed at a sponsor-designated laboratory for T790M mutation in EGFR.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants with study drug assignment designated according to initial randomization, regardless of treatment received. The participants under the category EGFR T790M Mutation are already included in the EGFR Mutant category.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	94	94
EGFR Status: Wild Type	65 69.1%	58 61.7%
EGFR Status: Mutant	11 11.7%	19 20.2%
EGFR T790M Mutation	0 0%	2 2.1%
EGFR Status: Unknown	18 19.1%	17 18.1%
KRAS Status: Wild Type	64 68.1%	57 60.6%
KRAS Status: Mutant	14 14.9%	17 18.1%
KRAS Status: Unknown	16 17%	20 21.3%

5. Other Pre-specified Outcome

Title	Soluble Protein Biomarkers Level
Description	Blood specimens were analyzed at a sponsor-designated laboratory for analysis of shed proteins/receptors related to Human Epidermal Growth Factor Receptor (HER) signaling (EGFR, HER-2, Epithelial-cadherin [E-cadherin]). The data collection after C12D1 was not performed, as there were too few participants across both treatment arms after C12D1.
Time Frame	Cycle (C) 1 Day (D) 1 (baseline), D1 of each subsequent cycle up to end of treatment (up to 121 weeks)

Outcome Measure Data

Analysis Population Description

Biomarker analysis population: participants who received >=1 dose and had baseline samples submitted as per Institutional Review Board/Independent Ethics Committee approval and participant consent. "N"(number of participants analyzed): participants evaluable for this measure; "n": participants evaluable at each time-point for each arm respectively.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	76	73
EGFR, C1D1 (n= 65, 66)	49.88 (7.513)	49.44 (9.286)
EGFR, C2D1 (n= 76, 73)	48.87 (6.985)	41.29 (8.132)
EGFR, C3D1 (n= 43, 53)	51.28 (6.925)	42.39 (8.072)
EGFR, C4D1 (n= 26, 39)	49.49 (8.41)	41.9 (8.793)
EGFR, C5D1 (n= 16, 29)	48.58 (5.801)	41.97 (7.974)
EGFR, C6D1 (n= 15, 27)	50.32 (7.073)	42.82 (8.014)
EGFR, C7D1 (n= 13, 26)	52.16 (7.449)	43.16 (9.13)
EGFR, C8D1 (n= 10, 21)	54.74 (10.73)	44.78 (9.673)
EGFR, C9D1 (n= 8, 17)	55.38 (12.888)	47.89 (10.854)
EGFR, C10D1 (n= 10, 17)	54.57 (9.244)	48.12 (13.105)
EGFR, C11D1 (n= 7, 14)	59.63 (14.624)	50.9 (13.667)
EGFR, C12D1 (n= 6, 13)	57.65 (11.503)	52.39 (12.976)
HER2, C1D1 (n= 65,66)	10.89 (15.44)	8.39 (2.05)
HER2, C2D1 (n= 76,73)	9.17 (4.946)	6.42 (2.12)
HER2, C3D1 (n= 43,53)	9.26 (6.383)	6.17 (1.703)
HER2, C4D1 (n= 26,39)	9.51 (6.958)	6.29 (1.716)
HER2, C5D1 (n= 16,29)	7.7 (1.79)	5.96 (1.342)
HER2, C6D1 (n= 15,27)	7.45 (2.414)	6.34 (1.428)
HER2, C7D1 (n= 13,26)	8.07 (2.262)	6.47 (1.773)
HER2, C8D1 (n= 10,21)	7.28 (1.279)	7.15 (3.168)
HER2, C9D1 (n= 8,17)	7.32 (1.204)	6.87 (2.205)
HER2, C10D1 (n= 10,17)	7.49 (1.618)	7.25 (2.883)
HER2, C11D1 (n= 7,14)	7.76 (1.735)	6.56 (1.333)
HER2, C12D1 (n= 6,13)	7.15 (1.57)	6.57 (1.587)
E-cadherin, C1D1 (n= 65,66)	51.71 (14.63)	56.13 (22.694)
E-cadherin, C2D1 (n= 76,73)	41.46 (14.982)	45.4 (18.149)
E-cadherin, C3D1 (n= 43,53)	42.58 (13.284)	42.28 (17.81)
E-cadherin, C4D1 (n= 26,39)	40.51 (12.384)	40.15 (16.105)
E-cadherin, C5D1 (n= 16,29)	37.58 (9.951)	38.15 (10.913)
E-cadherin, C6D1 (n= 15,27)	36.78 (7.695)	39.16 (10.301)
E-cadherin, C7D1 (n= 13,26)	38.33 (9.675)	39.47 (11.977)
E-cadherin, C8D1 (n= 10,21)	43.6 (11.661)	40.94 (13.698)
E-cadherin, C9D1 (n= 8,17)	40.26 (8.146)	38.97 (12.517)
E-cadherin, C10D1 (n= 10,17)	40.29 (15.742)	45.85 (12.244)
E-cadherin, C11D1 (n= 7,14)	35.9 (9.239)	39.44 (8.968)
E-cadherin, C12D1 (n= 6,13)	35.48 (8.637)	40.3 (12.433)

6. Other Pre-specified Outcome

Title	Trough Plasma Concentration (Ctrough) of Dacomitinib (PF-00299804)
Description	Only participants from "Dacomitinib" treatment arm were planned to be analyzed for this outcome.
Time Frame	C1D10-14, C2D1, C3D1, C4D1

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis population: all participants who received >=1 dose of study medication, with treatment assignments designated according to actual study treatment received, and from whom at least 1 PK sample was obtained. Here "n" signifies participants who were evaluable at specified time-point.

Arm/Group Title	Dacomitinib
Arm/Group Description	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	63
C1D10-14 (n= 63)	71.94 (37.496)
C2D1 (n= 60)	65.50 (33.292)
C3D1 (n= 44)	59.28 (30.089)
C4D1 (n= 31)	57.79 (26.206)

7. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS: Time in weeks from randomization to date of objective disease progression or death due to any cause, whichever occurred first. PFS was calculated as (first event date or last known event-free date [if the event date unavailable] minus the date of randomization plus 1) divided by 7. Objective progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST), as at least 20 percent (%) increase in the sum of longest dimensions (LDs) of target lesions, taking as reference the smallest sum of LD recorded since the treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time Frame	Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized participants with study drug assignment designated according to initial randomization, regardless of treatment received.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	94	94
Median (95% Confidence Interval) [weeks]	8.3	12.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erlotinib, Dacomitinib
	Comments	Total 128 events (progression/death) provided 80% power to detect a hazard ratio (HR) of 1.45 (Erlotinib versus Dacomitinib arm) with 1-sided alpha=0.10.This represented a 45% improvement in true median PFS. HR and 95% confidence interval estimated from stratified Cox Regression;2-sided p-value was based on stratified log-rank test with epidermal growth factor receptor (EGFR) status, Kirsten Rat Sarcoma status (KRAS), baseline Eastern Cooperative Oncology Group (ECOG) as stratification factors
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments	2-Sided.
	Method	Log Rank
	Comments	Adjusted for the stratification factors: EGFR status, KRAS status and baseline ECOG performance status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.657
	Confidence Interval	(2-Sided) 95%; 0.472 to 0.914
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated HR was for the Dacomitinib arm versus the Erlotinib arm.

8. Secondary Outcome

Title	Percentage of Participants With Objective Response
Description	Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.0. CR: disappearance of all target and non-target lesions. PR: at least 30 % decrease in sum of the LDs of target lesion, taking as reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.
Time Frame	Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants with study drug assignment designated according to initial randomization, regardless of treatment received.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	94	94
Number (95% Confidence Interval) [percentage of participants]	5.3 5.6%	17.0 18.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erlotinib, Dacomitinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	2-Sided.
	Method	Chi-squared
	Comments	Unadjusted.

9. Secondary Outcome

Title	Best Overall Response (BOR)
Description	Number of participants with BOR according to RECIST version 1.0: CR= disappearance of all target and non-target lesions. PR= at least 30% decrease in sum of LDs of target lesion, taking as reference baseline sum LD. Stable/no response= neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LDs since treatment started. Objective progression= at least a 20% increase in sum of LDs of target lesions, taking as reference the smallest sum of LDs recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.
Time Frame	Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants with study drug assignment designated according to initial randomization, regardless of treatment received.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	94	94
Complete Response	0 0%	1 1.1%
Partial Response	5 5.3%	15 16%
Stable/No Response	37 39.4%	32 34%
Objective Progression	49 52.1%	30 31.9%
Indeterminate	3 3.2%	16 17%

10. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in weeks from first documentation of objective tumor response to objective tumor progression or symptomatic deterioration or death due to any cause, whichever occurred first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or symptomatic deterioration or death due to any cause or last known progression-free date [if none of the event dates available] minus the date of the first CR or PR [which ever occurred first] that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame	Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks

Outcome Measure Data

Analysis Population Description

Analysis population included sub-set of participants from ITT population who had a confirmed objective tumor response (CR or PR).

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	5	16
Median (95% Confidence Interval) [weeks]	40.1	71.9

11. Secondary Outcome

Title	Overall Survival (OS)
Description	Time in weeks from randomization to date of death due to any cause. OS was calculated as (the death date or last known alive date (if death date unavailable) minus the date of randomization plus 1) divided by 7.
Time Frame	Baseline until end of treatment (15 August 2014); followed up every 8 weeks after discontinuation from study treatment.

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants with study drug assignment designated according to initial randomization, regardless of treatment received.

Arm/Group Title	Erlotinib	Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Measure Participants	94	94
Median (95% Confidence Interval) [weeks]	32.3	41.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erlotinib, Dacomitinib
	Comments	HR and its 95% confidence interval were estimated from stratified Cox Regression and 2-sided p-value was based on the stratified log-rank test with EGFR status, KRAS status and baseline ECOG as stratification factors.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.252
	Comments	2-Sided.
	Method	Log Rank
	Comments	Adjusted by stratification factors: EGFR status, KRAS status and baseline ECOG performance status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.822
	Confidence Interval	(2-Sided) 95%; 0.587 to 1.151
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated HR was for the Dacomitinib arm versus the Erlotinib arm.

Adverse Events

Time Frame	Adverse events (AEs) were recorded from the time that the participant provided informed consent through and including 28 calendar days after the last administration of the investigational product.
Adverse Event Reporting Description	The same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Erlotinib		Dacomitinib
Arm/Group Description	Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.		Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
All Cause Mortality
	Erlotinib		Dacomitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Erlotinib		Dacomitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/94 (31.9%)		34/93 (36.6%)
Blood and lymphatic system disorders
Anaemia	1/94 (1.1%)		0/93 (0%)
Gastrointestinal disorders
Abdominal pain	2/94 (2.1%)		0/93 (0%)
Diarrhoea	2/94 (2.1%)		2/93 (2.2%)
Gastrointestinal haemorrhage	0/94 (0%)		1/93 (1.1%)
Nausea	0/94 (0%)		1/93 (1.1%)
Vomiting	1/94 (1.1%)		2/93 (2.2%)
General disorders
Chest pain	1/94 (1.1%)		0/93 (0%)
Disease progression	12/94 (12.8%)		9/93 (9.7%)
Fatigue	0/94 (0%)		1/93 (1.1%)
Malaise	1/94 (1.1%)		0/93 (0%)
Non-cardiac chest pain	0/94 (0%)		1/93 (1.1%)
Cyst	0/94 (0%)		1/93 (1.1%)
Infections and infestations
Abscess	0/94 (0%)		1/93 (1.1%)
Herpes zoster	0/94 (0%)		1/93 (1.1%)
Infected dermal cyst	1/94 (1.1%)		0/93 (0%)
Lower respiratory tract infection	0/94 (0%)		1/93 (1.1%)
Lung infection	0/94 (0%)		1/93 (1.1%)
Parotitis	1/94 (1.1%)		0/93 (0%)
Pneumonia	4/94 (4.3%)		6/93 (6.5%)
Pneumonia bacterial	0/94 (0%)		1/93 (1.1%)
Sepsis	0/94 (0%)		1/93 (1.1%)
Skin infection	0/94 (0%)		1/93 (1.1%)
Injury, poisoning and procedural complications
Fall	0/94 (0%)		1/93 (1.1%)
Hip fracture	1/94 (1.1%)		0/93 (0%)
Metabolism and nutrition disorders
Cachexia	1/94 (1.1%)		0/93 (0%)
Dehydration	1/94 (1.1%)		1/93 (1.1%)
Hypercalcaemia	1/94 (1.1%)		0/93 (0%)
Hypovolaemia	0/94 (0%)		1/93 (1.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion	0/94 (0%)		1/93 (1.1%)
Nervous system disorders
Altered state of consciousness	0/94 (0%)		1/93 (1.1%)
Syncope	1/94 (1.1%)		0/93 (0%)
Psychiatric disorders
Confusional state	1/94 (1.1%)		2/93 (2.2%)
Mental status changes	1/94 (1.1%)		0/93 (0%)
Psychotic disorder	0/94 (0%)		1/93 (1.1%)
Renal and urinary disorders
Haematuria	1/94 (1.1%)		0/93 (0%)
Renal failure	0/94 (0%)		1/93 (1.1%)
Renal failure acute	0/94 (0%)		1/93 (1.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/94 (1.1%)		0/93 (0%)
Cough	0/94 (0%)		1/93 (1.1%)
Dyspnoea	3/94 (3.2%)		8/93 (8.6%)
Haemoptysis	1/94 (1.1%)		1/93 (1.1%)
Pneumonitis	0/94 (0%)		1/93 (1.1%)
Pulmonary embolism	3/94 (3.2%)		1/93 (1.1%)
Pulmonary haemorrhage	0/94 (0%)		1/93 (1.1%)
Respiratory failure	1/94 (1.1%)		1/93 (1.1%)
Wheezing	1/94 (1.1%)		0/93 (0%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	0/94 (0%)		1/93 (1.1%)
Vascular disorders
Deep vein thrombosis	1/94 (1.1%)		0/93 (0%)
Hypotension	0/94 (0%)		1/93 (1.1%)
Other (Not Including Serious) Adverse Events
	Erlotinib		Dacomitinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/94 (98.9%)		93/93 (100%)
Blood and lymphatic system disorders
Anaemia	5/94 (5.3%)		6/93 (6.5%)
Eye disorders
Dry eye	3/94 (3.2%)		6/93 (6.5%)
Conjunctivitis	3/94 (3.2%)		9/93 (9.7%)
Gastrointestinal disorders
Abdominal pain upper	7/94 (7.4%)		2/93 (2.2%)
Cheilitis	1/94 (1.1%)		5/93 (5.4%)
Constipation	12/94 (12.8%)		9/93 (9.7%)
Diarrhoea	46/94 (48.9%)		67/93 (72%)
Dry mouth	8/94 (8.5%)		9/93 (9.7%)
Dyspepsia	8/94 (8.5%)		3/93 (3.2%)
Mouth ulceration	5/94 (5.3%)		3/93 (3.2%)
Nausea	21/94 (22.3%)		20/93 (21.5%)
Stomatitis	10/94 (10.6%)		27/93 (29%)
Vomiting	14/94 (14.9%)		11/93 (11.8%)
General disorders
Asthenia	11/94 (11.7%)		13/93 (14%)
Chest pain	13/94 (13.8%)		5/93 (5.4%)
Fatigue	33/94 (35.1%)		24/93 (25.8%)
Mucosal inflammation	7/94 (7.4%)		23/93 (24.7%)
Oedema peripheral	4/94 (4.3%)		6/93 (6.5%)
Pain	6/94 (6.4%)		5/93 (5.4%)
Infections and infestations
Paronychia	8/94 (8.5%)		24/93 (25.8%)
Upper respiratory tract infection	6/94 (6.4%)		3/93 (3.2%)
Urinary tract infection	6/94 (6.4%)		5/93 (5.4%)
Investigations
Weight decreased	13/94 (13.8%)		18/93 (19.4%)
Metabolism and nutrition disorders
Decreased appetite	29/94 (30.9%)		27/93 (29%)
Musculoskeletal and connective tissue disorders
Back pain	10/94 (10.6%)		11/93 (11.8%)
Pain in extremity	2/94 (2.1%)		5/93 (5.4%)
Nervous system disorders
Dizziness	9/94 (9.6%)		3/93 (3.2%)
Dysgeusia	7/94 (7.4%)		7/93 (7.5%)
Headache	8/94 (8.5%)		3/93 (3.2%)
Psychiatric disorders
Insomnia	5/94 (5.3%)		2/93 (2.2%)
Respiratory, thoracic and mediastinal disorders
Cough	21/94 (22.3%)		17/93 (18.3%)
Dysphonia	0/94 (0%)		6/93 (6.5%)
Dyspnoea	16/94 (17%)		20/93 (21.5%)
Epistaxis	2/94 (2.1%)		7/93 (7.5%)
Haemoptysis	3/94 (3.2%)		9/93 (9.7%)
Skin and subcutaneous tissue disorders
Acne	11/94 (11.7%)		12/93 (12.9%)
Alopecia	3/94 (3.2%)		9/93 (9.7%)
Dermatitis acneiform	54/94 (57.4%)		60/93 (64.5%)
Dry skin	15/94 (16%)		22/93 (23.7%)
Erythema multiforme	4/94 (4.3%)		10/93 (10.8%)
Exfoliative rash	14/94 (14.9%)		16/93 (17.2%)
Nail disorder	1/94 (1.1%)		7/93 (7.5%)
Palmar-plantar erythrodysaesthesia syndrome	5/94 (5.3%)		11/93 (11.8%)
Pruritus	15/94 (16%)		14/93 (15.1%)
Skin fissures	2/94 (2.1%)		9/93 (9.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.