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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.

Author information

  • 1Suzanne 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.

Abstract

PURPOSE:

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 AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00730639.

PMID:
24590637
[PubMed - indexed for MEDLINE]
PMCID:
PMC4811023
Free PMC Article
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