SWOG S0635 and S0636: Phase II trials in advanced-stage NSCLC of erlotinib (OSI-774) and bevacizumab in bronchioloalveolar carcinoma (BAC) and adenocarcinoma with BAC features (adenoBAC), and in never-smokers with primary NSCLC adenocarcinoma (adenoCa).

Abstract

7517 Background: Despite recent changes to lung adenoCa pathologic classification, adv stage BAC remains a definable and clinically applicable entity. Patients (pts) with BAC, as well as never-smoking (NS) pts with adv lung adenoCa, have emerged as relevant clinical subpopulations with a high probability of clinical benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), likely related to the high proportion of activating mutations in the EGFR gene in such pts. Based on these results and the potential for increased clinical activity conferred by addition of B to E, SWOG initiated a pair of phase II trials of this combination in pts with adv BAC (S0635) or NS pts with adv lung adenoCa (S0636). Methods: NS pts with BAC or adenoBAC were preferentially enrolled on S0636. A total of 78 and 85 eligible pts were enrolled and treated on the S0635 and S0636 trials, respectively. Patients received E 150 mg PO daily and B 15 mg/kg IV q21 days until progression or prohibitive toxicity. Tumor tissue submission for pathologic review and assessment of molecular markers was mandated. Results: Pt demographics of the two trials are as shown in the table below. RECIST response rate among 61 BAC pts on S0635 with measurable disease was 18%, and among 53 NS pts on S0636, it was 47%. Median progression-free survival is 5 and 8 months (mo) on S0635 and S0636, respectively; median overall survival (OS) is 17 and 26 mo on S0635 and S0636, respectively. Toxicity consisted primarily of rash, diarrhea, and hypertension; no treatment-related deaths were reported. Molecular marker studies will be presented separately. Conclusions: In populations selected by clinical parameters, E withB is associated with modest toxicity and encouraging clinical efficacy that exceeded the prespecified OS threshold of 16 mo in studies of both adv BAC and NS pts, exceeding two years in NS pts. [Table: see text]