A phase II study of erlotinib as first-line treatment of advanced non-small cell lung cancer

Abstract

7073 Background: Erlotinib (TarcevaTM) is an orally available selective EGFR tyrosine-kinase inhibitor. In patients with advanced NSCLC, 2nd/3rd-line erlotinib significantly prolonged survival (Shepherd et al. ASCO 2004) with a response rate (RR) of 9%. This phase II trial evaluated the efficacy and safety of 1st line erlotinib in patients with advanced NSCLC. Methods: Chemotherapy-naïve, stage IIIB/IV, PS 0–2, NSCLC patients have been enrolled to receive erlotinib 150 mg/day until disease progression or withdrawal. The primary endpoint of the study was the rate of non-progression in >50% of patients after 6 weeks of treatment. Secondary endpoints included objective response, disease control rate, duration of response, time to progression, survival and safety. Exploratory analyses included QoL, EGFR expression and mutation analysis, and FDG-PET response at 3 weeks in a subset of patients. Results: 54 patients were enrolled from January to July 2004 from 3 institutions. 53 patients received erlotinib and are assessable. Demographics: M/F 20/33; median age 61; PS 0/1/2 13/32/8; pathology adeno 23, squamous cell 9, bronchioloalveolar (BAC) 6, large cell 8, other 7; smoking status current/former/never 10/25/18. The non-progression rate was 55%. Best response was: 1CR, 12 PR, 16 SD, 17 PD, 7 NE (RR 24.5%; 95% CI 13.8–38.3). To date, 14 patients have not progressed and 12 have been treated for 6 months or longer. Responses were observed in males (1CR, 3 PR) and in females (9 PR), mostly in adenocarcinoma (7) and in BAC (4), in non or former smokers (12). The most common adverse events were diarrhea and rash (28 patients each), primarily of grades 1/2. Five patients had a grade 3 event: 2 rash, 1 lethargy, 1 diarrhea, 1 conjunctivitis. No grade 4 events. Bilirubin elevation was reported for 6 patients (4 grade 1, 2 grade 2). EGFR and PI3K mutations were not found in 15 patients so far assessed (1 responder) but 8 had K-ras mutations. Conclusions: Erlotinib is active and well tolerated as first-line monotherapy in advanced NSCLC. Responses were seen in both genders including a CR in a male with adenocarcinoma, but were more common in women, adenocarcinomas/BAC and non-smokers. Further assessment of erlotinib in this setting is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche AstraZeneca, Roche AstraZeneca, Roche AstraZeneca, Roche