Trial Outcomes & Findings for Dacomitinib (PF-00299804) As A Single Oral Agent In Selected Patients With Adenocarcinoma Of The Lung (NCT NCT00818441)

Last Updated: 2019-01-08

Results Overview

PFS at Month 4 was defined as percentage of participants who were alive and event free (event defined as progressive disease \[PD\] or death due to any cause, whichever occurs first) at 4 months after the first dose of study treatment. Documentation of progression was based on Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria. PD = greater than or equal to (\>=) 20 percent (%) increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the start of treatment, or the appearance of 1 or more new lesions, or unequivocal progression in non-target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

119 participants

Primary outcome timeframe

Baseline up to Month 4

Results posted on

2019-01-08

Participant Flow

Participant milestones

Participant milestones
Measure	Dacomitinib: Cohort A Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Overall Study STARTED	89	30
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	89	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Dacomitinib: Cohort A Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Overall Study Death	69	26
Overall Study Other	5	0
Overall Study Lost to Follow-up	2	1
Overall Study Withdrawal by Subject	2	0
Overall Study Adverse Event	0	1
Overall Study Study terminated by sponsor	11	2

Baseline Characteristics

Dacomitinib (PF-00299804) As A Single Oral Agent In Selected Patients With Adenocarcinoma Of The Lung

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dacomitinib: Cohort A n=89 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=30 Participants Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.	Total n=119 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 11.18 • n=99 Participants	57.3 years STANDARD_DEVIATION 10.88 • n=107 Participants	61.3 years STANDARD_DEVIATION 11.30 • n=206 Participants
Sex: Female, Male Female	60 Participants n=99 Participants	15 Participants n=107 Participants	75 Participants n=206 Participants
Sex: Female, Male Male	29 Participants n=99 Participants	15 Participants n=107 Participants	44 Participants n=206 Participants

PRIMARY outcome

Timeframe: Baseline up to Month 4

Population: As-enrolled population included all participants who were enrolled in the study.

Outcome measures

Outcome measures
Measure	Dacomitinib: Cohort A n=89 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Progression-Free Survival (PFS) at Month 4: Cohort A	76.9 percentage of participants Interval 66.4 to 84.4	—

SECONDARY outcome

Timeframe: Baseline up to Month 4

PFS at Month 4 was defined as percentage of patients who were alive and event free (event defined as PD or death due to any cause, whichever occurs first) at 4 months after the first dose of study treatment. Documentation of progression was based on RECIST v1.0 criteria. PD: \>=20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the start of treatment, or the appearance of 1 or more new lesions, or unequivocal progression in non-target lesions.

Outcome measures

Outcome measures
Measure	Dacomitinib: Cohort A n=30 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Progression-Free Survival (PFS) at Month 4: Cohort B	24.9 percent chance of being event-free Interval 11.0 to 41.7	—

SECONDARY outcome

Timeframe: Baseline until progression or initiation of new anti-cancer therapy or death, assessed at baseline, at the end of Cycle 1, Cycle 2, and then every other cycle.

Population: As-enrolled population included all participants who were enrolled in the study.

PFS was defined as the time in months from the first dosing date to the date of first documentation of progression or death due to any cause, whichever occurs first. PFS was calculated as (first event date \[if not reached, censored date as the last known event-free date\] minus first dosing date plus 1) divided by 30.44. PD: \>= 20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the start of treatment, or the appearance of 1 or more new lesions. Documentation of progression was determined from objective disease assessment based on RECIST v1.0 criteria.

Outcome measures

Outcome measures
Measure	Dacomitinib: Cohort A n=89 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=30 Participants Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Progression-Free Survival (PFS)	11.5 months Interval 9.0 to 12.9	2.6 months Interval 1.8 to 3.7

SECONDARY outcome

Timeframe: Baseline until progression or initiation of new anti-cancer therapy or death, assessed at baseline, at the end of Cycle 1, Cycle 2, and then every other cycle.

Population: Response-evaluable population included all enrolled participants who received at least 1 dose of study medication, had an adequate baseline tumor assessment, and had at least 1 on-study tumor assessment after the first dosing.

BOR: best response recorded from treatment start until disease progression/recurrence based on RECIST v1.0. Complete Response (CR): disappearance of all lesions. Partial Response (PR): \>=30% decrease in sum of longest diameters of target lesions taking as reference baseline sum of longest diameters, associated to non-progressive disease response for non target lesions. PD: \>=20% increase in sum of longest diameters of target lesions taking as reference smallest sum of longest diameters since treatment start, or appearance of \>=1 new lesion, or unequivocal progression in non-target lesions. Stable disease (SD): neither shrinkage for CR/PR nor increase for PD taking as reference smallest sum of longest diameters since treatment start. CR and PR had to be confirmed on a follow up imaging assessment \>=4 weeks after the initial objective documentation of the response. SD must have met the SD criteria at least once after start of treatment in a minimum interval of 6 weeks.

Outcome measures

Outcome measures
Measure	Dacomitinib: Cohort A n=89 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=30 Participants Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Best Overall Response (BOR) Complete Response	1 participants	0 participants
Best Overall Response (BOR) Partial Response	47 participants	3 participants
Best Overall Response (BOR) Stable Disease	27 participants	11 participants
Best Overall Response (BOR) Progressive Disease	13 participants	13 participants
Best Overall Response (BOR) Indeterminate	1 participants	3 participants

SECONDARY outcome

Timeframe: Baseline until progression or initiation of new anti-cancer therapy or death, assessed at baseline, at the end of Cycle 1, Cycle 2, and then every other cycle.

Population: DR was calculated for a subgroup of participants from the response-evaluable population, who had confirmed objective tumor response (CR or PR).

Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause, whichever occurs first. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause \[if not reached, censored date\] minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.44. DR was calculated for a subgroup of participants with a confirmed objective tumor response.

Outcome measures

Outcome measures
Measure	Dacomitinib: Cohort A n=48 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=3 Participants Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Duration of Response (DR)	12.9 months Interval 9.6 to 18.4	12.4 months Interval 11.0 to 13.9

SECONDARY outcome

Timeframe: Randomization until death or last date known to be alive.

Population: As-enrolled population included all participants who were enrolled in the study.

Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date or last alive date minus the date of first dose of study medication plus 1) divided by 30.44. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).

Outcome measures

Outcome measures
Measure	Dacomitinib: Cohort A n=89 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=30 Participants Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Overall Survival (OS)	29.5 months Interval 22.8 to 35.6	9.3 months Interval 6.6 to 20.8

SECONDARY outcome

Timeframe: Baseline (Cycle [C]1 Day 1), up to C75

Population: Patient reported Outcome (PRO) analysis set:participants who received at least (\>=) 1 dose of study medication (as-treated population), had baseline PRO assessments, \>=1 on-study assessment submitted. 'N' (number of participants analyzed)=participants evaluable for this measure.n=participants evaluable at specified time points for given parameter.

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status (GHS), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). For GHS, functional scales, symptom scales and single items, scores were averaged, transformed to 0-100 scale; higher score=better level of functioning/health or greater degree of symptoms. Improvement was defined as a mean increase from baseline of ≥10 for GHS and functional scales or a mean decrease from baseline of ≤10 for symptom scales. Worsened was defined as a mean decrease from baseline of ≤10 for GHS and functional scales or a mean increase from baseline of ≥10 for symptom scales. Stable was a mean change from baseline of \<10.

Outcome measures

Outcome measures
Measure	Dacomitinib: Cohort A n=84 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=29 Participants Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score GHS: Improved	22 number of participants	3 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score GHS: Worsened	21 number of participants	11 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score GHS: Stable	39 number of participants	15 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Physical Functioning: Improved	19 number of participants	4 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Physical Functioning: Worsened	22 number of participants	7 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Physical Functioning: Stable	42 number of participants	18 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Role Functioning: Inproved	24 number of participants	7 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Role Functioning: Worsened	30 number of participants	10 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Role Functioning: Stable	29 number of participants	12 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Cognitive Functioning: Improved	15 number of participants	6 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Cognitive Functioning: Worsened	24 number of participants	9 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Cognitive Functioning: Stable	44 number of participants	14 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Emotional Functioning: Improved	22 number of participants	4 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Emotional Functioning: Worsened	23 number of participants	7 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Emotional Functioning: Stable	38 number of participants	18 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Social Functioning: Improved	20 number of participants	8 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Social Functioning: Worsened	25 number of participants	9 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Social Functioning: Stable	37 number of participants	12 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Fatigue: Improved	30 number of participants	7 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Fatigue: Worsened	28 number of participants	11 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Fatigue: Stable	25 number of participants	11 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Pain: Improved	32 number of participants	8 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Pain: Worsened	24 number of participants	11 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Pain: Stable	27 number of participants	10 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Nausea and Vomiting: Improved	16 number of participants	3 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Nausea and Vomiting: Worsened	14 number of participants	11 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Nausea and Vomiting: Stable	53 number of participants	15 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Dyspnea: Improved	28 number of participants	2 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Dyspnea: Worsened	16 number of participants	5 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Dyspnea: Stable	39 number of participants	22 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Appetite Loss: Improved	22 number of participants	3 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Appetite Loss: Worsened	25 number of participants	13 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Appetite Loss: Stable	36 number of participants	13 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Insomnia: Improved	31 number of participants	10 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Insomnia: Worsened	19 number of participants	5 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Insomnia: Stable	33 number of participants	14 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Constipation: Improved	23 number of participants	8 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Constipation: Worsened	9 number of participants	4 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Constipation: Stable	50 number of participants	17 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Diarrhea: Improved	6 number of participants	0 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Diarrhea: Worsened	58 number of participants	22 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Diarrhea: Stable	19 number of participants	7 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Financial Difficulties: Improved	14 number of participants	4 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Financial Difficulties: Worsened	18 number of participants	3 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score Financial Difficulties: Stable	51 number of participants	22 number of participants

SECONDARY outcome

Timeframe: Baseline (C1D1) up to C75

Population: PRO analysis set: participants who received \>=1 dose of study medication (as-treated population), had baseline PRO assessments, \>=1 on-study assessment submitted. n=participants evaluable at specified time points for given parameter.

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 experienced during past 1 week. 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 ). Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results are reported for coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, and other pain. Improvement was defined as a mean decrease from baseline of ≤10. Worsened was defined as a mean increase from baseline of ≥10. Stable was a mean change from baseline of \<10.

Outcome measures

Outcome measures
Measure	Dacomitinib: Cohort A n=84 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=29 Participants Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Dyspnoea: Improved	21 number of participants	5 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Dyspnoea: Worsened	16 number of participants	8 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Dyspnoea: Stable	47 number of participants	16 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Coughing: Improved	36 number of participants	12 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Coughing: Worsened	11 number of participants	4 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Coughing: Stable	37 number of participants	13 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Haemoptysis: Improved	4 number of participants	1 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Haemoptysis: Worsened	2 number of participants	2 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Haemoptysis: Stable	78 number of participants	26 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Sore Mouth: Improved	5 number of participants	2 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Sore Mouth: Worsened	45 number of participants	18 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Sore Mouth: Stable	34 number of participants	9 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Dysphagia: Imporved	8 number of participants	2 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Dysphagia: Worsened	13 number of participants	7 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Dysphagia: Stable	63 number of participants	19 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Peripheral Neuropathy: Improved	11 number of participants	6 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Peripheral Neuropathy: Worsened	28 number of participants	8 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Peripheral Neuropathy: Stable	45 number of participants	15 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Alopecia: Improved	6 number of participants	10 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Alopecia: Worsened	35 number of participants	2 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Alopecia: Stable	42 number of participants	16 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Chest: Improved	26 number of participants	7 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Chest: Worsened	11 number of participants	5 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Chest: Stable	47 number of participants	16 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Arm or Shoulder: Improved	23 number of participants	5 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Arm or Shoulder: Worsened	14 number of participants	5 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Arm or Shoulder: Stable	47 number of participants	18 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Other Parts: Improved	28 number of participants	7 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Other Parts: Worsened	20 number of participants	9 number of participants
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13) Score Pain in Other Parts: Stable	33 number of participants	12 number of participants

SECONDARY outcome

Timeframe: Predose on C1D14, C2D1, C3D1, C4D1

Population: Pharmacokinetic (PK) analysis set: all participants who received at least 1 dose of study medication at selected PK sites from whom at least 1 PK sample were obtained. 'N' (number of participants analyzed) = participants who were evaluable for this measure at any time point. n = participants evaluable at given time points for specified dose.

Results for Ctrough were summarized as per the dose received during given cycle: no dose (treatment interruption at any cycle due to treatment-related toxicity), dacomitinib 15 mg (dacomitinib 15 mg at any cycle due to treatment-related toxicity at higher doses), 30 mg (dacomitinib 30 mg at any cycle as starting dose or dose reduction due to treatment-related toxicity at higher doses), 45 mg (dacomitinib 45 mg at any cycle as starting dose or dose escalation due to satisfactory toleration of dacomitinib 30 mg treatment).

Outcome measures

Adverse Events

Dacomitinib: Cohort A

Serious events: 29 serious events

Other events: 89 other events

Deaths: 0 deaths

Dacomitinib: Cohort B

Serious events: 9 serious events

Other events: 30 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	Dacomitinib: Cohort A n=84 Participants Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=30 Participants Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C1D14: No Dose (Cohort A n=5; Cohort B n=5)	48.30 nanogram per milliliter (ng/mL) Standard Deviation 53.225	52.04 nanogram per milliliter (ng/mL) Standard Deviation 26.656
Trough Plasma Concentrations (Ctrough) of Dacomitinib C1D14: 30 mg (Cohort A n=28; Cohort B n=2)	56.61 nanogram per milliliter (ng/mL) Standard Deviation 25.795	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C1D14: 45 mg (Cohort A n=51; Cohort B n=20)	76.50 nanogram per milliliter (ng/mL) Standard Deviation 30.261	74.22 nanogram per milliliter (ng/mL) Standard Deviation 27.617
Trough Plasma Concentrations (Ctrough) of Dacomitinib C2D1: No Dose (Cohort A n=4; Cohort B n=2)	27.41 nanogram per milliliter (ng/mL) Standard Deviation 19.526	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C2D1: 15 mg (Cohort A n=1; Cohort B n=0)	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C2D1: 30 mg (Cohort A n=31; Cohort B n=6)	54.45 nanogram per milliliter (ng/mL) Standard Deviation 22.120	51.78 nanogram per milliliter (ng/mL) Standard Deviation 21.027
Trough Plasma Concentrations (Ctrough) of Dacomitinib C2D1: 45 mg (Cohort A n=42; Cohort B n=11)	69.98 nanogram per milliliter (ng/mL) Standard Deviation 26.899	79.63 nanogram per milliliter (ng/mL) Standard Deviation 22.437
Trough Plasma Concentrations (Ctrough) of Dacomitinib C3D1: No Dose (Cohort A n=5; Cohort B n=1)	41.80 nanogram per milliliter (ng/mL) Standard Deviation 32.179	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C3D1: 15 mg (Cohort A n=2; Cohort B n=0)	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C3D1: 30 mg (Cohort A n=31; Cohort B n=4)	49.13 nanogram per milliliter (ng/mL) Standard Deviation 19.726	58.43 nanogram per milliliter (ng/mL) Standard Deviation 21.009
Trough Plasma Concentrations (Ctrough) of Dacomitinib C3D1: 45 mg (Cohort A n=31; Cohort B n=8)	73.03 nanogram per milliliter (ng/mL) Standard Deviation 35.452	84.67 nanogram per milliliter (ng/mL) Standard Deviation 34.287
Trough Plasma Concentrations (Ctrough) of Dacomitinib C4D1: No Dose (Cohort A n=3; Cohort B n=1)	37.80 nanogram per milliliter (ng/mL) Standard Deviation 24.908	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C4D1: 15 mg (Cohort A n=6; Cohort B n=0)	21.92 nanogram per milliliter (ng/mL) Standard Deviation 6.7514	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C4D1: 30 mg (Cohort A n=33; Cohort B n=2)	55.27 nanogram per milliliter (ng/mL) Standard Deviation 20.856	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.
Trough Plasma Concentrations (Ctrough) of Dacomitinib C4D1: 45 mg (Cohort A n=25; Cohort B n=7)	56.02 nanogram per milliliter (ng/mL) Standard Deviation 23.749	83.57 nanogram per milliliter (ng/mL) Standard Deviation 48.302
Trough Plasma Concentrations (Ctrough) of Dacomitinib C2D1: 25 mg (Cohort A n=0; Cohort B n=1)	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.	NA nanogram per milliliter (ng/mL) Standard Deviation NA Mean and standard deviation of fewer than 3 participants was not considered meaningful, hence not summarized.

Serious adverse events
Measure	Dacomitinib: Cohort A n=89 participants at risk Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=30 participants at risk Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Blood and lymphatic system disorders Iron deficiency anaemia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure congestive	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Left ventricular dysfunction	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Congenital, familial and genetic disorders Haemorrhagic arteriovenous malformation	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal hernia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	3.4% 3/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	10.0% 3/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Dysphagia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intestinal obstruction	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 2/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Stomatitis	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 2/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	3.4% 3/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Disease progression	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholecystitis acute	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastroenteritis viral	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpes zoster	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Infection	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lower respiratory tract infection	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Paronychia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Limb injury	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Transaminases increased	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Decreased appetite	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage II	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Syncope	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Confusional state	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Menorrhagia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events
Measure	Dacomitinib: Cohort A n=89 participants at risk Participants who had adenocarcinoma of lung, had not received prior systemic therapy and were either nonsmokers, former light smokers or were known to have an epidermal growth factor receptor (EGFR)-activating mutation, received dacomitinib 45 milligram (mg) or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per investigator's judgment. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg. Dose interruption for treatment-related toxicity was also allowed as per investigator's discretion.	Dacomitinib: Cohort B n=30 participants at risk Participants who had human epidermal growth factor receptor 2 (HER2) gene amplification or HER2 mutation, advanced non-small cell lung cancer (NSCLC) of any histology and had received prior chemotherapy or prior EGFR-targeted therapy, received dacomitinib 45 mg or 30 mg tablet orally daily in cycles of 28 days until progression of disease, unacceptable toxicity, or participant withdrawal. Participants who had not received prior therapy for advanced NSCLC, received 30 mg daily and participants who had received prior systemic therapy for advanced NSCLC, received 45 mg daily as starting dose. Dose escalated to 45 mg in participants after at least 8 weeks of therapy who had started treatment at 30 mg and were tolerating treatment for at least 4 consecutive weeks as per judgment of the investigator. Dose modifications for treatment-related toxicity were allowed for up to 2 dose reductions (to 30 mg and then to 15 mg) if the participant started at 45 mg.
Eye disorders Vitreous floaters	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal discomfort	6.7% 6/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	23.6% 21/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	16.7% 5/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Anaemia	5.6% 5/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Febrile neutropenia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Iron deficiency anaemia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukopenia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphadenopathy	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Microcytic anaemia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Neutropenia	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure congestive	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Left ventricular dysfunction	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Palpitations	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Pericardial effusion	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Ear pain	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders External ear pain	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Hearing impaired	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Tinnitus	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Blepharitis	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Chalazion	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Conjunctivitis	4.5% 4/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Dry eye	20.2% 18/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 2/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye irritation	3.4% 3/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye oedema	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye pain	3.4% 3/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye pruritus	3.4% 3/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eye swelling	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eyelash thickening	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Eyelid pain	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Growth of eyelashes	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Keratitis	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Lacrimation increased	6.7% 6/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Ocular hyperaemia	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Trichiasis	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Vision blurred	6.7% 6/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 2/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Eye disorders Visual impairment	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal distension	2.2% 2/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.3% 1/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	9.0% 8/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	6.7% 2/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain lower	1.1% 1/89 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/30 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.