A Phase II Study of Erlotinib as Initial Treatment for Patients with Stage IIIB-IV Non-small Cell Lung Cancer

Introduction: Erlotinib improves survival in patients with advanced non-small cell lung cancer who have been previously treated with systemic chemotherapy. The current trial was designed to evaluate erlotinib as a primary therapy before chemotherapy in patients with minimally restricted eligibility criteria. Methods: Eligibility criteria included stage IIIB/IV or recurrent non-small cell lung cancer, no prior chemotherapy for systemic disease, performance status = 0 to 1, no history of brain metastases, and weight loss less than 10%. Patients received erlotinib 150 mg/d until objective or symptomatic progression when they were offered conventional chemotherapy. The primary end point was progression-free survival. Results: Forty patients were accrued. The median age was 65 years, 35 had performance status = 1, 8 were never-smoker, and 23 were former smokers. Histologies were adenocarcinoma in 22 and squamous cell in six. The major toxicity was rash (grade 1, 12; grade 2. 16; grade 3, 3). Partial responses were observed in six (15%), stable in 11 (28%), and progressive disease in 23 (58%). The median time on erlotinib was 8 weeks. The median survival was 50 weeks with 1, 2, and 3 years survivals of 44%, 18%, and 16%. Retrospective epidermal growth factor receptor mutational analysis was performed in 18 subjects and four mutations (22%) were identified. Only 25 patients have received subsequent chemotherapy (too early, 4; refused, 9; and unable because of performance status, 2), and, of these, 9 (36%) achieved unconfirmed responses. Conclusions: Despite a modest response rate, lack of enrichment for never-smokers and absence of conventional chemotherapy in many patients, the median and long-term survivals were comparable with those expected after conventional sequencing of chemotherapy. Erlotinib as initial therapy was well tolerated and warrants randomized evaluation as first-line treatment for advanced lung cancer.