Southwestern Oncology Group Phase II Trial (S0526) of Pemetrexed in Bronchioloalveolar Carcinoma Subtypes of Advanced Adenocarcinoma

BackgroundPemetrexed, a multitargeted antifolate drug, is an active agent in non–small-cell lung cancer (NSCLC), especially adenocarcinomas. Based on preclinical data supporting the relevance of alpha-folate receptors in adenocarcinoma of the bronchioloalveolar carcinoma (BAC) subtype, this trial was designed to assess pemetrexed in patients with this pathologic subtype of lung adenocarcinoma.Patients and MethodsPatients with histologically confirmed stage IIIB (with malignant pleural effusion) or stage IV adenocarcinoma with BAC features or pure BAC were eligible. Treatment consisted of pemetrexed, 500 mg/m², administered intravenously every 21 days.ResultsOf 27 patients enrolled, 24 were eligible and assessable for adverse events: Toxicity was primarily hematologic, consisting of leukopenia/neutropenia, thrombocytopenia, and anemia. The median follow-up among patients still alive (n = 8) was 35 months (range, 26-47 months). Among 17 patients with measurable disease, the response rate was 23% (all partial responses; 95% confidence interval CI], 10%-56%). The median progression-free survival (PFS) and overall survival (OS) were 6 and 25 months, respectively.ConclusionPemetrexed is active and well tolerated and, in patients with adenocarcinoma BAC subtypes, likely related to its underlying mechanism of action as a multitargeted antifolate drug.