• Hossein Borghaei, Corey J Langer, Shirish Gadgeel, Vassiliki A Papadimitrakopoulou, Amita Patnaik, Steven F Powell, Ryan D Gentzler, Renato G Martins, James P Stevenson, Shadia I Jalal, Amit Panwalkar, James Chih-Hsin Yang, Matthew Gubens, Lecia V Sequist, Mark M Awad, Joseph Fiore, Sanatan Saraf, Steven M Keller, and Leena Gandhi.
• Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. Electronic address: Hossein.borghaei@fccc.edu.
• J Thorac Oncol. 2019 Jan 1; 14 (1): 124-129.

IntroductionCohort 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.MethodsA 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).ResultsAs 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.ConclusionsThe 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.Copyright © 2018 International Association for the Study of Lung Cancer. All rights reserved.

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