Maintenance pemetrexed (Pem) plus best supportive care (BSC) versus placebo (Plac) plus BSC: A randomized phase III study in advanced non-small cell lung cancer (NSCLC).

CRA8000 Background: Pemetrexed's efficacy, favorable tolerability profile, and ease of administration provided a strong rationale for evaluation as maintenance therapy in patients (pts) with advanced NSCLC. We present the final analyses for all outcomes, including overall survival (OS), from a phase III study of Pem vs. Plac (Ciuleanu, J Clin Oncol 26, 2008, A 8011) in pts with stage IIIB/IV NSCLC who had not progressed on four cycles of platinum-based chemotherapy.,In this double-blind trial, pts were randomized 2:1 to receive Pem (500 mg/m, day 1) plus BSC or Plac plus BSC in 21-day cycles until disease progression. All pts received vitamin B, folic acid, and dexamethasone. The final OS analysis was performed using an unadjusted Cox model. Overall α = 0.05 for PFS and OS.,In the 663 randomized pts (Pem 441: Plac 222), Pem resulted in significantly better OS (13.4 vs. 10.6 mos [HR 0.79, 95% CI: 0.65-0.95, P = 0.012]). As reported earlier, Pem also had better PFS (P <0.00001) and response (P <0.001) ( Table ). The improvements in PFS and OS were observed primarily in patients with non-squamous histology (PFS HR = 0.47 and OS HR = 0.70). Treatment by histology interaction for OS was significant (P = 0.038). Drug-related grade 3/4 toxicities were higher for Pem (16% vs 4%; P <0.001); specifically, fatigue (5% vs 0.5%) and neutropenia (2.9% vs. 0%). Grade 3/4 toxicities did not increase significantly in pts who received ≥6 and ≥10 cycles of Pem. There were no Pem-related deaths. Fewer pts in the Pem arm (51.5% vs 67.1%; P <0.001) received systemic post-discontinuation therapy.,Pem maintenance therapy is well tolerated and offers superior OS and PFS compared with Plac, making it a new treatment paradigm for patients with advanced NSCLC who respond to initial therapy. This trial further validates that Pem has greater efficacy in patients with non-squamous histology. [Table: see text] [Table: see text].