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.
No abstract
No abstract
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.