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Onco Targets Ther. 2018 Dec 14;11:9081-9089. doi: 10.2147/OTT.S171693. eCollection 2018.

Encorafenib/binimetinib for the treatment of BRAF-mutant advanced, unresectable, or metastatic melanoma: design, development, and potential place in therapy.

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Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA,


Major advances in the understanding of the pathophysiology of melanoma have led to a new era of melanoma treatment with targeted therapy and immunotherapies. Since 2011, four new classes of medications with unique mechanisms of action have been approved, which allow melanoma to be treated at many different stages in its development. These include the checkpoint inhibitors anti-PD1/PDL-1 and anti-CTLA4, as well as BRAF inhibitors and MEK inhibitors. The latter two were developed to directly inhibit key components in the MAP kinase pathway with significant breakthrough in the treatment of metastatic and unresectable melanoma. In this review, we discuss the development of targeted therapy of melanoma up to the latest agents encorafenib and binimetinib, including mechanisms of action, adverse effects, and the latest data on treatment response. Current ongoing trials will continue to elucidate these medications and their ultimate impact on melanoma therapy.


BRAF; LGX818; MEK; MEK162; advanced melanoma; binimetinib; encorafenib

Conflict of interest statement

Disclosure JS has no conflicts of interest to disclose related to this work. ZE is a member of the Medical Advisory Board for Array BioPharma and Regeneron, and JSZ is a member of the Medical Advisory Board for Delcath Systems. He also receives grant funding from Delcath Systems. He is a primary investigator on clinical trials funded by Delcath Systems, Amgen, Castle Biosciences, Provectus, Philogen, and Novartis. He consults for Amgen, Castle Biosciences, and Philogen. He is a member of the speaker’s bureau for Amgen, Array BioPharma, and Sun Pharma. Finally, he has participated on advisory boards for Amgen, Merck & Co., Inc., and Array BioPharma. The authors report no other conflicts of interest in this work.

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