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Review
. 2017 Feb 13:6:1-10.
doi: 10.2147/ITT.S110479. eCollection 2017.

First-line treatment of metastatic melanoma: role of nivolumab

Jeremy Force  1 , April Ks Salama  2
Affiliations
Review

First-line treatment of metastatic melanoma: role of nivolumab

Jeremy Force et al. Immunotargets Ther. .

Abstract

Historically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients. We discuss advances in immunotherapy while focusing on the use of nivolumab alone and in combination with other agents, including ipilimumab in advanced melanoma. One major goal in melanoma research is to optimize combination strategies allowing for more patients to experience benefit while minimizing toxicity. A better understanding of the optimal sequencing, combinations, and mechanisms underlying the development of resistance may provide evidence for rational clinical trial designs of novel immunotherapy strategies in melanoma and other cancer subtypes.

Keywords: BRAF; PD-1; PD-L1; checkpoint; immunotherapy; pembrolizumab; resistance.

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Conflict of interest statement

Disclosure April KS Salama, MD, received funding for the research from Merck, BMS, Genentech, Reata, Celldex, and Immunocore and is a consultant to BMS. The other author reports no conflicts of interest in this work.

Figures

Figure 1
Figure 1
(A) APC presents tumor-associated antigens to circulating T cells via MHC complex binding to TCR. However, a co-stimulatory signal, provided upon the binding of CD28/B7 is required for T cell activation. Following T-cell stimulation, PD-1 expression occurs. PD-L1 and PD-L2 expressed on tumor cells can interact with PD-1 on T cells in the tumor microenvironment causing T-cell down regulation and tumor immune evasion. (B) Anti-PD-1 inhibits PD-1 binding to PD-L1 and PD-L2 allowing the immune system to recognize tumors as foreign and induce immune-mediated tumor cellular death. Abbreviations: APC, antigen-presenting cell; MHC, major histocompatibility complex; TCR, T-cell receptor; CD, cluster designation; PD-1, programmed death-1; PD-L, programmed cell death ligand.
See this image and copyright information in PMC

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