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J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3.

Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab.

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Suzanne L. Topalian, William H. Sharfman, Julie R. Brahmer, Evan J. Lipson, Janis M. Taube, and Drew M. Pardoll, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol and Harriet M. Kluger, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; David F. McDermott, Beth Israel Deaconess Medical Center; Donald P. Lawrence, Massachusetts General Hospital Cancer Center; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Richard D. Carvajal, Memorial Sloan-Kettering Cancer Center, New York, NY; Michael B. Atkins, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; John D. Powderly, Carolina BioOncology Institute, Huntersville, NC; Philip D. Leming, The Christ Hospital Cancer Center, Cincinnati, OH; Igor Puzanov and Jeffrey A. Sosman, Vanderbilt University Medical Center, Nashville, TN; David C. Smith, University of Michigan, Ann Arbor, MI; and Jon M. Wigginton, Georgia D. Kollia, and Ashok Gupta, Bristol-Myers Squibb, Princeton, NJ.



Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued.


Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation.


Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative.


Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.


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