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

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

Time frame: Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks

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

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

Time frame: Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks

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

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

Time frame: Baseline up to Cycle 44 (Week 188)

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

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

Time frame: Baseline up to Cycle 44 (Week 188)

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

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

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

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

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

Time frame: Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks

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

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

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

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

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

Time frame: Baseline until disease progression or death, assessed at Cycle 2, 3, 4, 5, 6, thereafter every other cycle up to end of treatment (121 weeks), followed by every 8 weeks >284 weeks

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

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

Time frame: Baseline

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

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

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

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

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

Time frame: C1D10-14, C2D1, C3D1, C4D1

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