Trial Outcomes & Findings for 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 (NCT NCT00769067)

Last Updated: 2015-10-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

188 participants

Primary outcome timeframe

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

Results posted on

2015-10-07

Participant Flow

Participant milestones

Participant milestones
Measure	Erlotinib Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Overall Study STARTED	94	94
Overall Study Treated	94	93
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	94	94

Reasons for withdrawal

Reasons for withdrawal
Measure	Erlotinib Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Overall Study Death	89	86
Overall Study Lost to Follow-up	3	1
Overall Study Study terminated by sponsor	1	3
Overall Study Other	1	3
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Erlotinib n=94 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=94 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Total n=188 Participants Total of all reporting groups
Age, Continuous	60.1 years STANDARD_DEVIATION 12.0 • n=5 Participants	59.9 years STANDARD_DEVIATION 9.5 • n=7 Participants	60.0 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	39 Participants n=7 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	55 Participants n=7 Participants	111 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Outcome measures
Measure	Erlotinib n=94 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=94 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Progression-Free Survival (PFS)	8.3 weeks Interval 7.9 to 11.7	12.4 weeks Interval 8.1 to 16.1

SECONDARY outcome

Timeframe: Baseline up to Cycle 44 (Week 188)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Erlotinib n=88 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=90 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
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) Constipation: Improved (n= 86, 85)	25 participants	32 participants
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) Constipation: Worsened (n= 86, 85)	16 participants	13 participants
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) Global QoL: Improved (n= 85, 85)	14 participants	11 participants
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) Global QoL: Worsened (n= 85, 85)	36 participants	34 participants
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) Global QoL: Stable (n= 85, 85)	35 participants	40 participants
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) Physical Functioning: Improved (n= 86, 88)	12 participants	14 participants
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) Physical Functioning: Worsened (n= 86, 88)	25 participants	24 participants
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) Physical Functioning: Stable (n= 86, 88)	49 participants	50 participants
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) Role Functioning: Improved (n= 86, 88)	18 participants	22 participants
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) Role Functioning: Worsened (n= 86, 88)	38 participants	31 participants
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) Role Functioning: Stable (n= 86, 88)	30 participants	35 participants
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) Cognitive Functioning: Improved (n= 86, 85)	13 participants	15 participants
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) Cognitive Functioning: Worsened (n= 86, 85)	21 participants	21 participants
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) Cognitive Functioning: Stable (n= 86, 85)	52 participants	49 participants
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) Emotional Functioning: Improved (n= 86, 85)	11 participants	21 participants
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) Emotional Functioning: Worsened (n= 86, 85)	27 participants	26 participants
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) Emotional Functioning: Stable (n= 86, 85)	48 participants	38 participants
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) Social Functioning: Improved (n= 86, 85)	24 participants	30 participants
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) Social Functioning: Worsened (n= 86, 85)	30 participants	19 participants
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) Social Functioning: Stable (n= 86, 85)	32 participants	36 participants
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) Fatigue: Improved (n= 86, 87)	18 participants	21 participants
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) Fatigue: Worsened (n= 86, 87)	38 participants	35 participants
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) Fatigue: Stable (n= 86, 87)	30 participants	31 participants
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) Pain: Improved (n= 86, 87)	19 participants	19 participants
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) Pain: Worsened (n= 86, 87)	30 participants	34 participants
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) Pain: Stable (n= 86, 87)	37 participants	34 participants
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) Nausea and Vomiting: Improved (n= 86, 87)	13 participants	13 participants
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) Nausea and Vomiting: Worsened (n= 86, 87)	27 participants	26 participants
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) Nausea and Vomiting: Stable (n= 86, 87)	46 participants	48 participants
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) Dyspnea: Improved (n= 86, 88)	23 participants	25 participants
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) Dyspnea: Worsened (n= 86, 88)	26 participants	25 participants
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) Dyspnea: Stable (n= 86, 88)	37 participants	38 participants
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) Loss of Appetite: Improved (n= 85, 87)	17 participants	19 participants
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) Loss of Appetite: Worsened (n= 85, 87)	41 participants	43 participants
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) Loss of Appetite: Stable (n= 85, 87)	27 participants	25 participants
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) Insomnia: Improved (n= 86, 87)	23 participants	22 participants
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) Insomnia: Worsened (n= 86, 87)	32 participants	33 participants
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) Insomnia: Stable (n= 86, 87)	31 participants	32 participants
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) Constipation: Stable (n= 86, 85)	45 participants	40 participants
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) Diarrhea: Improved (n= 86, 85)	6 participants	4 participants
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) Diarrhea: Worsened (n= 86, 85)	52 participants	67 participants
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) Diarrhea: Stable (n= 86, 85)	28 participants	14 participants
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) Financial Difficulties: Improved (n= 85, 85)	18 participants	17 participants
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) Financial Difficulties: Worsened (n= 85, 85)	21 participants	17 participants
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) Financial Difficulties: Stable (n= 85, 85)	46 participants	51 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Erlotinib n=88 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=89 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
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) Dyspnoea: Stable (n= 85, 87)	38 participants	43 participants
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) Haemoptysis: Improved (n= 85, 86)	5 participants	8 participants
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) Haemoptysis: Worsened (n= 85, 86)	10 participants	10 participants
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) Alopecia: Improved (n= 84, 87)	20 participants	21 participants
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) Dyspnoea: Improved (n= 85, 87)	18 participants	24 participants
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) Dyspnoea: Worsened (n= 85, 87)	29 participants	20 participants
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) Coughing: Improved (n= 85, 87)	24 participants	37 participants
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) Coughing: Worsened (n= 85, 87)	20 participants	20 participants
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) Coughing: Stable (n= 85, 87)	41 participants	30 participants
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) Haemoptysis: Stable (n= 85, 86)	70 participants	68 participants
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) Sore mouth: Improved (n= 85, 87)	3 participants	5 participants
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) Sore mouth: Worsened (n= 85, 87)	38 participants	58 participants
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) Sore mouth: Stable (n= 85, 87)	44 participants	24 participants
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) Dysphagia: Improved (n= 85, 87)	7 participants	6 participants
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) Dysphagia: Worsened (n= 85, 87)	24 participants	35 participants
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) Dysphagia: Stable (n= 85, 87)	54 participants	46 participants
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) Peripheral: Improved (n= 85, 87)	22 participants	27 participants
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) Peripheral: Worsened (n= 85, 87)	23 participants	20 participants
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) Peripheral: Stable (n= 85, 87)	40 participants	40 participants
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) Alopecia: Worsened (n= 84, 87)	13 participants	21 participants
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) Alopecia: Stable (n= 84, 87)	51 participants	45 participants
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) Pain in chest: Improved (n= 85, 87)	26 participants	30 participants
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) Pain in chest: Worsened (n= 85, 87)	21 participants	13 participants
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) Pain in chest: Stable (n= 85, 87)	38 participants	44 participants
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) Pain in arm or Shoulder: Improved (n= 85, 87)	19 participants	28 participants
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) Pain in arm or Shoulder: Worsened (n= 85, 87)	27 participants	17 participants
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) Pain in arm or Shoulder: Stable (n= 85, 87)	39 participants	42 participants
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) Pain in other parts: Improved (n= 83, 86)	26 participants	23 participants
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) Pain in other parts: Worsened (n= 83, 86)	27 participants	28 participants
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) Pain in other parts: Stable (n= 83, 86)	30 participants	35 participants

SECONDARY outcome

Timeframe: Cycle (C) 1 Day (D) 1 (baseline), C1D10-14, D1 of subsequent cycles up to C44

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Erlotinib n=87 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=91 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Dermatology Life Quality Index (DLQI) C5D1 (n= 25, 38)	3.56 units on a scale Standard Deviation 3.61	5.37 units on a scale Standard Deviation 6.08
Dermatology Life Quality Index (DLQI) C10D1 (n= 11, 17)	3.36 units on a scale Standard Deviation 3.04	5.88 units on a scale Standard Deviation 7.37
Dermatology Life Quality Index (DLQI) C20D1 (n= 2, 10)	3.50 units on a scale Standard Deviation 3.54	6.50 units on a scale Standard Deviation 8.57
Dermatology Life Quality Index (DLQI) C21D1 (n= 2, 9)	3.50 units on a scale Standard Deviation 2.12	7.33 units on a scale Standard Deviation 7.76
Dermatology Life Quality Index (DLQI) C22D1 (n= 1, 7)	1.00 units on a scale Standard Deviation NA No measure of dispersion calculated as there is only 1 participant (n=1)	2.14 units on a scale Standard Deviation 3.67
Dermatology Life Quality Index (DLQI) C23D1 (n= 1, 7)	1.00 units on a scale Standard Deviation NA No measure of dispersion calculated as there is only 1 participant (n=1)	3.71 units on a scale Standard Deviation 3.99
Dermatology Life Quality Index (DLQI) C24D1 (n= 1, 7)	3.00 units on a scale Standard Deviation NA No measure of dispersion calculated as there is only 1 participant (n=1)	2.57 units on a scale Standard Deviation 4.08
Dermatology Life Quality Index (DLQI) C25D1 (n= 1, 6)	8.00 units on a scale Standard Deviation NA No measure of dispersion calculated as there is only 1 participant (n=1)	2.83 units on a scale Standard Deviation 4.45
Dermatology Life Quality Index (DLQI) C26D1 (n= 0, 6)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	2.67 units on a scale Standard Deviation 4.13
Dermatology Life Quality Index (DLQI) C27D1 (n= 0, 6)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	3.33 units on a scale Standard Deviation 3.98
Dermatology Life Quality Index (DLQI) C28D1 (n= 0, 6)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	3.17 units on a scale Standard Deviation 3.82
Dermatology Life Quality Index (DLQI) C29D1 (n= 0, 6)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	5.33 units on a scale Standard Deviation 4.59
Dermatology Life Quality Index (DLQI) C30D1 (n= 0, 5)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	4.20 units on a scale Standard Deviation 5.12
Dermatology Life Quality Index (DLQI) C31D1 (n= 0, 5)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	4.20 units on a scale Standard Deviation 4.97
Dermatology Life Quality Index (DLQI) C32D1 (n= 0, 4)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	2.75 units on a scale Standard Deviation 2.50
Dermatology Life Quality Index (DLQI) C33D1 (n= 0, 4)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	3.00 units on a scale Standard Deviation 2.94
Dermatology Life Quality Index (DLQI) C34D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	4.00 units on a scale Standard Deviation 1.41
Dermatology Life Quality Index (DLQI) C35D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	12.50 units on a scale Standard Deviation 13.44
Dermatology Life Quality Index (DLQI) C36D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	1.50 units on a scale Standard Deviation 2.12
Dermatology Life Quality Index (DLQI) C37D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	1.50 units on a scale Standard Deviation 2.12
Dermatology Life Quality Index (DLQI) C38D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	0.50 units on a scale Standard Deviation 0.71
Dermatology Life Quality Index (DLQI) C39D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	0.00 units on a scale Standard Deviation 0.00
Dermatology Life Quality Index (DLQI) C40D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	0.50 units on a scale Standard Deviation 0.71
Dermatology Life Quality Index (DLQI) C41D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	0.00 units on a scale Standard Deviation 0.00
Dermatology Life Quality Index (DLQI) C42D1 (n= 0, 2)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	0.50 units on a scale Standard Deviation 0.71
Dermatology Life Quality Index (DLQI) C43D1 (n= 0, 1)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	3.00 units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)
Dermatology Life Quality Index (DLQI) C44D1 (n= 0, 0)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)	NA units on a scale Standard Deviation NA No measure of dispersion calculated as there are no participants (n=0)
Dermatology Life Quality Index (DLQI) C1D1 (n= 87, 91)	0.70 units on a scale Standard Deviation 1.97	0.88 units on a scale Standard Deviation 2.38
Dermatology Life Quality Index (DLQI) C1D10-14 (n=68, 81)	4.35 units on a scale Standard Deviation 6.25	3.06 units on a scale Standard Deviation 4.94
Dermatology Life Quality Index (DLQI) C2D1 (n= 80, 82)	5.16 units on a scale Standard Deviation 6.29	3.91 units on a scale Standard Deviation 4.07
Dermatology Life Quality Index (DLQI) C3D1 (n= 63, 63)	4.08 units on a scale Standard Deviation 5.67	5.52 units on a scale Standard Deviation 6.65
Dermatology Life Quality Index (DLQI) C4D1 (n= 39, 43)	3.97 units on a scale Standard Deviation 4.59	5.95 units on a scale Standard Deviation 6.38
Dermatology Life Quality Index (DLQI) C6D1 (n= 16, 27)	4.13 units on a scale Standard Deviation 4.80	5.37 units on a scale Standard Deviation 6.67
Dermatology Life Quality Index (DLQI) C7D1 (n= 13, 27)	4.38 units on a scale Standard Deviation 4.07	4.93 units on a scale Standard Deviation 6.54
Dermatology Life Quality Index (DLQI) C8D1 (n= 11, 24)	4.64 units on a scale Standard Deviation 3.14	5.33 units on a scale Standard Deviation 6.23
Dermatology Life Quality Index (DLQI) C9D1 (n= 11, 19)	3.82 units on a scale Standard Deviation 3.34	4.84 units on a scale Standard Deviation 5.76
Dermatology Life Quality Index (DLQI) C11D1 (n= 10, 15)	5.60 units on a scale Standard Deviation 5.13	6.73 units on a scale Standard Deviation 7.57
Dermatology Life Quality Index (DLQI) C12D1 (n= 7, 14)	6.71 units on a scale Standard Deviation 5.62	5.50 units on a scale Standard Deviation 6.99
Dermatology Life Quality Index (DLQI) C13D1 (n= 7, 13)	5.57 units on a scale Standard Deviation 4.08	5.08 units on a scale Standard Deviation 7.90
Dermatology Life Quality Index (DLQI) C14D1 (n= 6, 12)	6.00 units on a scale Standard Deviation 3.95	6.00 units on a scale Standard Deviation 7.35
Dermatology Life Quality Index (DLQI) C15D1 (n= 6, 12)	4.67 units on a scale Standard Deviation 3.78	5.92 units on a scale Standard Deviation 7.40
Dermatology Life Quality Index (DLQI) C16D1 (n= 5, 11)	5.40 units on a scale Standard Deviation 3.91	5.36 units on a scale Standard Deviation 8.18
Dermatology Life Quality Index (DLQI) C17D1 (n= 4, 11)	5.00 units on a scale Standard Deviation 4.24	5.55 units on a scale Standard Deviation 7.85
Dermatology Life Quality Index (DLQI) C18D1 (n= 4, 10)	3.00 units on a scale Standard Deviation 2.16	7.30 units on a scale Standard Deviation 9.08
Dermatology Life Quality Index (DLQI) C19D1 (n= 4, 9)	4.50 units on a scale Standard Deviation 2.38	7.22 units on a scale Standard Deviation 7.73

SECONDARY outcome

Timeframe: 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

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

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.

Outcome measures

Outcome measures
Measure	Erlotinib n=94 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=94 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Percentage of Participants With Objective Response	5.3 percentage of participants Interval 1.7 to 12.0	17.0 percentage of participants Interval 10.1 to 26.2

SECONDARY outcome

Timeframe: 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

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

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.

Outcome measures

Outcome measures
Measure	Erlotinib n=94 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=94 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Best Overall Response (BOR) Complete Response	0 participants	1 participants
Best Overall Response (BOR) Partial Response	5 participants	15 participants
Best Overall Response (BOR) Stable/No Response	37 participants	32 participants
Best Overall Response (BOR) Objective Progression	49 participants	30 participants
Best Overall Response (BOR) Indeterminate	3 participants	16 participants

SECONDARY outcome

Timeframe: 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

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

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.

Outcome measures

Outcome measures
Measure	Erlotinib n=5 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=16 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Duration of Response (DR)	40.1 weeks Interval 24.7 to 72.0	71.9 weeks Interval 23.6 to 112.1

SECONDARY outcome

Timeframe: Baseline until end of treatment (15 August 2014); followed up every 8 weeks after discontinuation from study treatment.

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

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.

Outcome measures

Outcome measures
Measure	Erlotinib n=94 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=94 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Overall Survival (OS)	32.3 weeks Interval 24.0 to 40.3	41.4 weeks Interval 30.4 to 48.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Erlotinib n=94 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=94 Participants Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation EGFR Status: Wild Type	65 participants	58 participants
Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation EGFR Status: Mutant	11 participants	19 participants
Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation EGFR T790M Mutation	0 participants	2 participants
Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation KRAS Status: Wild Type	64 participants	57 participants
Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation KRAS Status: Mutant	14 participants	17 participants
Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation KRAS Status: Unknown	16 participants	20 participants
Number of Participants With Kirsten Rat Sarcoma (KRAS) and Epidermal Growth Factor Receptor (EGFR) Status and EGFR T790M Mutation EGFR Status: Unknown	18 participants	17 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Cycle (C) 1 Day (D) 1 (baseline), D1 of each subsequent cycle up to end of treatment (up to 121 weeks)

Population: 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.

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.

Outcome measures

OTHER_PRE_SPECIFIED outcome

Timeframe: C1D10-14, C2D1, C3D1, C4D1

Population: 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.

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

Outcome measures

Outcome measures
Measure	Erlotinib n=63 Participants Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Trough Plasma Concentration (Ctrough) of Dacomitinib (PF-00299804) C2D1 (n= 60)	65.50 ng/mL Standard Deviation 33.292	—
Trough Plasma Concentration (Ctrough) of Dacomitinib (PF-00299804) C1D10-14 (n= 63)	71.94 ng/mL Standard Deviation 37.496	—
Trough Plasma Concentration (Ctrough) of Dacomitinib (PF-00299804) C3D1 (n= 44)	59.28 ng/mL Standard Deviation 30.089	—
Trough Plasma Concentration (Ctrough) of Dacomitinib (PF-00299804) C4D1 (n= 31)	57.79 ng/mL Standard Deviation 26.206	—

Adverse Events

Erlotinib

Serious events: 30 serious events

Other events: 93 other events

Deaths: 0 deaths

Dacomitinib

Serious events: 34 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

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

Serious adverse events
Measure	Erlotinib n=94 participants at risk Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=93 participants at risk Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Blood and lymphatic system disorders Anaemia	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Gastrointestinal disorders Abdominal pain	2.1% 2/94 • 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. 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.	0.00% 0/93 • 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. 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.
Gastrointestinal disorders Diarrhoea	2.1% 2/94 • 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. 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.	2.2% 2/93 • 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. 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.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Gastrointestinal disorders Nausea	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Gastrointestinal disorders Vomiting	1.1% 1/94 • 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. 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.	2.2% 2/93 • 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. 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.
General disorders Chest pain	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
General disorders Disease progression	12.8% 12/94 • 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. 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.	9.7% 9/93 • 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. 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.
General disorders Fatigue	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
General disorders Malaise	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
General disorders Non-cardiac chest pain	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Infections and infestations Abscess	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Infections and infestations Herpes zoster	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Infections and infestations Infected dermal cyst	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Infections and infestations Lower respiratory tract infection	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Infections and infestations Lung infection	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Infections and infestations Parotitis	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Infections and infestations Pneumonia	4.3% 4/94 • 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. 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.	6.5% 6/93 • 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. 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.
Infections and infestations Pneumonia bacterial	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Infections and infestations Sepsis	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Infections and infestations Skin infection	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Injury, poisoning and procedural complications Fall	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Injury, poisoning and procedural complications Hip fracture	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Metabolism and nutrition disorders Cachexia	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Metabolism and nutrition disorders Dehydration	1.1% 1/94 • 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. 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.	1.1% 1/93 • 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. 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.
Metabolism and nutrition disorders Hypercalcaemia	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Nervous system disorders Altered state of consciousness	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Nervous system disorders Syncope	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Psychiatric disorders Confusional state	1.1% 1/94 • 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. 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.	2.2% 2/93 • 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. 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.
Psychiatric disorders Mental status changes	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Psychiatric disorders Psychotic disorder	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Renal and urinary disorders Haematuria	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Renal and urinary disorders Renal failure	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
General disorders Cyst	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Renal and urinary disorders Renal failure acute	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.1% 1/94 • 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. 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.	0.00% 0/93 • 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. 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.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/94 • 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. 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.	1.1% 1/93 • 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. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.2% 3/94 • 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. 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.	8.6% 8/93 • 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. 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.

Other adverse events
Measure	Erlotinib n=94 participants at risk Erlotinib 150 milligram (mg) tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.	Dacomitinib n=93 participants at risk Dacomitinib (PF-00299804) 45 mg tablet orally once daily continuously in 28-day cycles until unacceptable toxicity, tumor progression or death.
Blood and lymphatic system disorders Anaemia	5.3% 5/94 • 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. 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.	6.5% 6/93 • 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. 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.
Eye disorders Dry eye	3.2% 3/94 • 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. 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.	6.5% 6/93 • 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. 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.
Gastrointestinal disorders Abdominal pain upper	7.4% 7/94 • 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. 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.	2.2% 2/93 • 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. 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.
Gastrointestinal disorders Cheilitis	1.1% 1/94 • 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. 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.	5.4% 5/93 • 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. 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.
Gastrointestinal disorders Constipation	12.8% 12/94 • 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. 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.	9.7% 9/93 • 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. 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.
Gastrointestinal disorders Diarrhoea	48.9% 46/94 • 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. 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.	72.0% 67/93 • 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. 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.
Gastrointestinal disorders Dry mouth	8.5% 8/94 • 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. 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.	9.7% 9/93 • 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. 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.
Gastrointestinal disorders Dyspepsia	8.5% 8/94 • 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. 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.	3.2% 3/93 • 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. 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.
Gastrointestinal disorders Mouth ulceration	5.3% 5/94 • 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. 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.	3.2% 3/93 • 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. 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.
Gastrointestinal disorders Nausea	22.3% 21/94 • 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. 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.	21.5% 20/93 • 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. 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.
Gastrointestinal disorders Stomatitis	10.6% 10/94 • 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. 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.	29.0% 27/93 • 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. 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.
Gastrointestinal disorders Vomiting	14.9% 14/94 • 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. 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.	11.8% 11/93 • 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. 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.
General disorders Asthenia	11.7% 11/94 • 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. 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.	14.0% 13/93 • 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. 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.
General disorders Chest pain	13.8% 13/94 • 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. 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.	5.4% 5/93 • 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. 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.
General disorders Fatigue	35.1% 33/94 • 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. 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.	25.8% 24/93 • 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. 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.
General disorders Mucosal inflammation	7.4% 7/94 • 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. 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.	24.7% 23/93 • 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. 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.
General disorders Oedema peripheral	4.3% 4/94 • 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. 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.	6.5% 6/93 • 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. 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.
General disorders Pain	6.4% 6/94 • 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. 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.	5.4% 5/93 • 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. 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.
Eye disorders Conjunctivitis	3.2% 3/94 • 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. 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.	9.7% 9/93 • 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. 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.
Infections and infestations Paronychia	8.5% 8/94 • 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. 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.	25.8% 24/93 • 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. 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.
Infections and infestations Upper respiratory tract infection	6.4% 6/94 • 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. 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.	3.2% 3/93 • 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. 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.
Infections and infestations Urinary tract infection	6.4% 6/94 • 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. 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.	5.4% 5/93 • 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. 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.
Investigations Weight decreased	13.8% 13/94 • 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. 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.	19.4% 18/93 • 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. 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.
Metabolism and nutrition disorders Decreased appetite	30.9% 29/94 • 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. 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.	29.0% 27/93 • 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. 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.
Musculoskeletal and connective tissue disorders Back pain	10.6% 10/94 • 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. 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.	11.8% 11/93 • 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. 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.
Musculoskeletal and connective tissue disorders Pain in extremity	2.1% 2/94 • 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. 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.	5.4% 5/93 • 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. 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.
Nervous system disorders Dizziness	9.6% 9/94 • 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. 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.	3.2% 3/93 • 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. 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.
Nervous system disorders Dysgeusia	7.4% 7/94 • 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. 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.	7.5% 7/93 • 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. 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.
Nervous system disorders Headache	8.5% 8/94 • 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. 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.	3.2% 3/93 • 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. 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.
Psychiatric disorders Insomnia	5.3% 5/94 • 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. 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.	2.2% 2/93 • 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. 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.
Respiratory, thoracic and mediastinal disorders Cough	22.3% 21/94 • 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. 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.	18.3% 17/93 • 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. 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.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/94 • 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. 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.	6.5% 6/93 • 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. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.0% 16/94 • 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. 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.	21.5% 20/93 • 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. 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.1% 2/94 • 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. 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.	7.5% 7/93 • 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. 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.
Respiratory, thoracic and mediastinal disorders Haemoptysis	3.2% 3/94 • 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. 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.	9.7% 9/93 • 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. 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.
Skin and subcutaneous tissue disorders Acne	11.7% 11/94 • 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. 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.	12.9% 12/93 • 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. 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.
Skin and subcutaneous tissue disorders Alopecia	3.2% 3/94 • 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. 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.	9.7% 9/93 • 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. 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.
Skin and subcutaneous tissue disorders Dermatitis acneiform	57.4% 54/94 • 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. 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.	64.5% 60/93 • 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. 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.
Skin and subcutaneous tissue disorders Dry skin	16.0% 15/94 • 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. 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.	23.7% 22/93 • 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. 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.
Skin and subcutaneous tissue disorders Erythema multiforme	4.3% 4/94 • 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. 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.	10.8% 10/93 • 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. 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.