A Study of Tarceva (Erlotinib) as First Line Therapy in Participants With Non-Small Cell Lung Cancer Harbouring Epidermal Growth Factor Receptor (EGFR) Mutations

Study Overview
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Brief Summary
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This open-label, single arm study will evaluate the safety and efficacy of Tarceva (erlotinib) as first-line therapy in participants with stage IV or recurrent non-small cell lung cancer who harbour epidermal growth factor receptor (EGFR) mutations. All participants will receive Tarceva 150 mg daily orally until disease progression or unacceptable toxicity occurs. At the investigator's discretion, participants may receive Tarceva beyond disease progression.

Official Title
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An Open-Label Multicenter Study of Erlotinib (Tarceva®) as First Line Therapy Until and Beyond RECIST Progression in NSCLC Patients Who Harbour EGFR Mutations

Conditions
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Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult participants, >/= 18 years of age Stage IV or recurrent non-small cell lung cancer (NSCLC) Presence of mutation(s) in exon 18 through exon 21 of epidermal growth factor receptor (EGFR), (except T790M single mutation only) Measurable disease (at least one lesion >= 10 mm in longest diameter) Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate hematological, renal and liver function Exclusion Criteria: Patients with T790M single mutation only Prior exposure to agents directed at the human epidermal receptor (HER) axis, e.g. erlotinib, gefitinib, cetuximab, trastuzumab Prior chemotherapy or systemic anti-cancer therapy for advanced NSCLC disease Symptomatic or uncontrolled central nervous system (CNS) metastases Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal or squamous cell carcinoma of the skin, or surgically treated localized prostate cancer, or surgically treated ductal cell carcinoma in situ of the breast Any significant ophthalmologic abnormality Pre-existing parenchymal lung disease such as pulmonary fibrosis Use of coumarins (for anti-coagulation therapy the use of low molecular weight heparin is recommended instead)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib<br>Erlotinib 150 mg daily | Drug: Erlotinib<br>* Erlotinib 150 mg was administered orally daily until disease progression or unacceptable toxicity.<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Per RECIST, v. 1.1 (PFS1) | PFS1 was defined as time from first dose until documented progressive disease (PD), assessed per Response Evaluation Criteria in Solid Tumors RECIST, v. 1.1, or death from any cause, whichever occurred first. PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions. | Approximately 68 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Per Investigator (PFS2) | PFS2 was defined as time from first study dose to off-erlotinib progressive disease (PD), assessed by the investigator based on overall clinical evaluation. | Approximately 68 months | 
| Objective Response Rate (ORR) for All Participants and Participants With EGFR Mutation E19del or L858R | ORR was defined as the occurrence of either a confirmed complete (CR) or a partial response (PR, as a best overall response), as determined by RECIST, v. 1.1 criteria. CR was defined as disappearance of all target lesions. PR was defined as least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. | Approximately 68 months | 
| Disease Control Rate (DCR) for All Participants and Participants With EGFR Mutation E19del or L858R | DCR was defined as CR + PR + Stable disease (SD). CR was defined as disappearance of all target lesions. PR was defined as least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions. | Approximately 68 months | 
| Progression-free Survival for Participants With EGFR Mutation E19del or L858R Per RECIST, v. 1.1 (PFS1) | PFS1 was defined as time from first dose until documented progressive disease (PD), assessed per Response Evaluation Criteria in Solid Tumors RECIST, v. 1.1, or death from any cause, whichever occurred first. PD was defined as: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline; an absolute increase of at least 5 mm in the sum of diameters of target lesions; and the appearance of one or more new lesions. | Approximately 68 months | 
| Overall Survival (OS) for All Participants and Participants With EGFR Mutation E19del or L858R | OS was defined as the time from baseline to the date of death from any cause. | Approximately 68 months | 
| Number of Participants With Adverse Events | An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. | Approximately 68 months | 
| Correlation Between EGFR Mutations in Plasma and Clinical Outcome (ORR/PFS/OS) | This outcome measure was not assessed. | Approximately 68 months |