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

Immunology

Journal of Cell Signaling

Author(s): Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD,

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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.
This article was published in J Clin Oncol and referenced in Journal of Cell Signaling

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