Late-Breaking Abstracts

Abstract

Both Pac+Cb+B and Pem+cisplatin are approved for first-line treatment of advanced NS-NSCLC. In a Ph 2 study, Pem+Cb+B showed promising overall survival (OS) and progression-free survival (PFS). The objective of this Ph 3 study was to compare Pem+Cb+B followed by Pem+B (Pem Arm) with Pac+Cb+B followed by B (Pac Arm) in pts with advanced NS-NSCLC. Materials/Methods: Pts with previously untreated stage IIIB/IV NS-NSCLC and ECOG performance status (PS) of 0-1 were randomized to receive Pem+Cb+B (Pem 500 mg/m 2 ; Cb AUC 6; B 15 mg/kg) and folic acid, vitamin B 12 and dexamethasone supplementation or Pac+Cb+B (Pac 200 mg/m 2 ; Cb AUC 6; B 15 mg/kg), and dexamethasone, diphenhydramine, and cimetidine or ranitidine premedications, every 3 weeks for up to 4 cycles. Pts continuing without progressive disease received maintenance Pem+B (Pem Arm) or B (Pac Arm). The primary endpoint of this superiority study was OS; secondary endpoints included PFS, objective response rate (ORR), disease control rate (DCR) and toxicity. The study assumed a hazard ratio (HR) of 0.80 and required 676 events in 900 pts to yield at least an 80% power to demonstrate superiority of Pem Arm over Pac Arm using a log-rank test with 1-sided type I error of 0.025. Efficacy analyses included all randomized pts; safety analyses included pts who received at least 1 dose of a study drug. Results: 939 pts were randomized to Pem+Cb+B (n=472) or Pac+Cb+B (n=467). Prognostic factors and characteristics were well balanced between arms: median age 64.7 years, 53.2% male, 55.9% PS 1, 90.0% stage IV NSCLC, 85.7% Caucasian, 79.2% adenocarcinoma and 11.6% never smokers. For Pem Arm vs Pac Arm, median OS was 12.6 vs 13.4 mo (HR 1.00, p=0.949); median PFS, 6.0 vs 5.6 mo (HR 0.83, p=0.012); ORR, 34.1% vs. 33.0%; and DCR, 65.9% vs 69.8%. Significantly more study drug-related grade 3/4 anemia (14.5% vs 2.7%), thrombocytopenia (23.3% vs 5.6%) and fatigue (10.9% vs 5.0%) were seen on Pem Arm; significantly more grade 3/4 neutropenia (40.6% vs 25.8%), febrile neutropenia (4.1% vs 1.4%), sensory neuropathy (4.1% vs 0) and complete alopecia (grade 2) (21.4 % vs 1.1%) were seen on Pac Arm. Study drug-related discontinuations due to SAE (2.7% vs 3.6%), AE (10.4% vs. 9.0%) and study drug-related deaths due to AE (1.8% vs 2.3%) were similar (Pem vs Pac, respectively). Exploratory KM analyses for pts treated with maintenance therapy were 17.7 vs 15.7 mo for OS and 8.6 vs 6.9 mo for PFS (Pem n=292 vs. Pac n=298 respectively). Conclusions: The primary endpoint of superior OS was not met in this trial, although Pem+Cb+B improved PFS. Toxicity profiles differed and both regimens demonstrated tolerability.