24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer

• Published in: Journal of thoracic oncology Vol. 14; no. 1; pp. 124 - 129
• Main Authors: Borghaei, Hossein, Langer, Corey J., Gadgeel, Shirish, Papadimitrakopoulou, Vassiliki A., Patnaik, Amita, Powell, Steven F., Gentzler, Ryan D., Martins, Renato G., Stevenson, James P., Jalal, Shadia I., Panwalkar, Amit, Yang, James Chih-Hsin, Gubens, Matthew, Sequist, Lecia V., Awad, Mark M., Fiore, Joseph, Saraf, Sanatan, Keller, Steven M., Gandhi, Leena
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2019; Copyright by the International Association for the Study of Lung Cancer
• Subjects: Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - adverse effects; Carboplatin - pharmacology; Carboplatin - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Combination therapy; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Nonsquamous non‒small cell lung cancer; Pembrolizumab; Pemetrexed - adverse effects; Pemetrexed - pharmacology; Pemetrexed - therapeutic use; Progression-Free Survival; Survival Rate; Time Factors; Chemotherapy; Pembrolizumab; Nonsquamous non‒small cell lung cancer; Combination therapy
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2018.08.004

Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.