• Naiyer A Rizvi, Matthew D Hellmann, Julie R Brahmer, Rosalyn A Juergens, Hossein Borghaei, Scott Gettinger, Laura Q Chow, David E Gerber, Scott A Laurie, Jonathan W Goldman, Frances A Shepherd, Allen C Chen, Yun Shen, Faith E Nathan, Christopher T Harbison, and Scott Antonia.
• Naiyer A. Rizvi and Matthew D. Hellmann, Memorial Sloan Kettering Cancer Center, New York, NY; Julie R. Brahmer, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Rosalyn A. Juergens, Juravinski Cancer Centre at McMaster University, Hamilton; Scott A. Laurie, Ottawa Hospital Cancer Centre, Ottawa; Frances A. Shepherd, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Hossein Borghaei, Fox Chase Cancer Center, Philadelphia, PA; Scott Gettinger, Yale Cancer Center, New Haven, CT; Laura Q. Chow, University of Washington, Seattle, WA; David E. Gerber, University of Texas Southwestern Medical Center, Dallas, TX; Jonathan W. Goldman, University of California, Los Angeles, Los Angeles, CA; Allen C. Chen, Yun Shen, Faith E. Nathan, and Christopher T. Harbison, Bristol-Myers Squibb, Princeton, NJ; and Scott Antonia, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. nar2144@cumc.columbia.edu.
• J. Clin. Oncol. 2016 Sep 1; 34 (25): 2969-79.

PurposeNivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC).Patients And MethodsPatients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progression-free survival rate (per Response Evaluation Criteria in Solid Tumors version 1.1); exploratory objectives included overall survival (OS) and response by tumor programmed death ligand-1 expression.ResultsNo dose-limiting toxicities occurred during the first 6 weeks of treatment. Forty-five percent of patients (25 of 56 patients) reported grade 3 or 4 treatment-related adverse events (AEs); 7% of patients (n = 4) had pneumonitis. Twenty-one percent of patients (n = 12) discontinued all study therapy as a result of treatment-related AEs. Objective response rates for nivolumab 10 mg/kg plus gemcitabine-cisplatin, nivolumab 10 mg/kg plus pemetrexed-cisplatin, nivolumab 10 mg/kg plus paclitaxel-carboplatin, and nivolumab 5 mg/kg plus paclitaxel-carboplatin were 33%, 47%, 47%, and 43%, respectively; 24-week progression-free survival rates were 51%, 71%, 38%, and 51%, respectively; 2-year OS rates were 25%, 33%, 27%, and 62%, respectively. Responses were achieved regardless of tumor programmed death ligand-1 expression.ConclusionThe safety profile of nivolumab plus PT-DC was consistent with that expected for individual agents; however, treatment discontinuation related to AEs was greater with the combination. Encouraging activity was observed, especially for the nivolumab 5 mg/kg plus paclitaxel-carboplatin group, with a 2-year OS rate of 62%.© 2016 by American Society of Clinical Oncology.

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