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J Clin Oncol. 2018 Feb 1;36(4):383-390. doi: 10.1200/JCO.2016.71.8023. Epub 2017 Jul 3.

Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial.

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James Larkin, Royal Marsden NHS Foundation Trust, London; Paul Lorigan, The Christie National Health Service Foundation Trust, Manchester, United Kingdom; David Minor, California Pacific Medical Center Research Institute; Adil Daud, University of California San Francisco, San Francisco; Bartosz Chmielowski, University of California, Santa Monica, CA; Sandra D'Angelo, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College; Jeffrey Weber, Perlmutter Cancer Center at New York University-Langone Medical Center, New York; Nikhil Khushalani, Roswell Park Cancer Institute, Buffalo, NY; Gerald Linette, Washington University, St. Louis, MO; Christopher D. Lao, University of Michigan, Ann Arbor, MI; Kenneth Grossmann, Huntsman Cancer Institute, Salt Lake City, UT; Mario Sznol, Yale Comprehensive Cancer Center, New Haven, CT; Jeffrey Sosman, Northwestern University, Chicago, IL; Dana Walker, George Kong, and Christine Horak, Bristol-Myers Squibb, Princeton, NJ; Bart Neyns, University Hospital, Vrije Universiteit Brussel, Brussels, Belgium; Michael Smylie, Cross Cancer Institute, Edmonton, Alberta; Wilson H. Miller Jr, Jewish General Hospital and Segal Cancer Centre, McGill University, Montreal, Quebc, Canada; Ralf Gutzmer, Medizinische Hochschule Hannover, Hannover; Jessica C. Hassel, Nationale Centrum für Tumorerkrankungen Heidelberg, Heidelberg; Dirk Schadendorf, University Hospital Essen, Essen, Germany; and Christoph Hoeller, Medical University of Vienna, Wien, Austria.


Purpose Until recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma. Patients and Methods Patients were stratified by programmed death-ligand 1 expression, BRAF status, and best prior cytotoxic T-lymphocyte antigen-4 therapy response, then randomly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator's choice chemotherapy (ICC; dacarbazine 1,000 mg/m2 every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m2 every 3 weeks). Patients were treated until they experienced progression or unacceptable toxicity, with follow-up of approximately 2 years. Results Two hundred seventy-two patients were randomly assigned to nivolumab (99% treated) and 133 to ICC (77% treated). More nivolumab-treated patients had brain metastases (20% v 14%) and increased lactate dehydrogenase levels (52% v 38%) at baseline; 41% of patients treated with ICC versus 11% of patients treated with nivolumab received anti-programmed death 1 agents after randomly assigned therapy. Median OS was 16 months for nivolumab versus 14 months for ICC (hazard ratio, 0.95; 95.54% CI, 0.73 to 1.24); median progression-free survival was 3.1 months versus 3.7 months, respectively (hazard ratio, 1.0; 95.1% CI, 0.78 to 1.436). Overall response rate (27% v 10%) and median duration of response (32 months v 13 months) were notably higher for nivolumab versus ICC. Fewer grade 3 and 4 treatment-related adverse events were observed in patients on nivolumab (14% v 34%). Conclusion Nivolumab demonstrated higher, more durable responses but no difference in survival compared with ICC. OS should be interpreted with caution as it was likely impacted by an increased dropout rate before treatment, which led to crossover therapy in the ICC group, and by an increased proportion of patients in the nivolumab group with poor prognostic factors.


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