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Review
. 2016 Jan;8(1):48-56.
doi: 10.1177/1758834015616934.

Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy

Zeynep Eroglu  1 , Antoni Ribas  2
Affiliations
Review

Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy

Zeynep Eroglu et al. Ther Adv Med Oncol. 2016 Jan.

Abstract

Treatment with BRAF inhibitors such as vemurafenib or dabrafenib in patients with advanced BRAFV600 mutated melanoma has shown objective tumor responses in approximately half of the patients. However, the duration of responses is limited in a majority of these patients, with progression-free survival rates around 6 months due to tumor progression from development of acquired resistance. Preclinical studies have suggested that concurrent inhibition of the BRAF kinases and MEK of the mitogen-activated protein kinase (MAPK) pathway could decrease MAPK-driven acquired resistance, resulting in longer duration of responses, higher rate of tumor responses, and a decrease in the cutaneous toxicities observed from paradoxical MAPK pathway activation with BRAF inhibitor monotherapy. This review provides an overview of the currently available clinical trial data on BRAF and MEK inhibitors together and in combinations with other therapeutic agents.

Keywords: BRAF inhibitors; MEK inhibitors; melanoma.

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Conflict of interest statement

Conflict of interest statement: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A.R.: consultant or advisory role with Merck Sharp & Dohme Corp., Amgen, Astellas, Daiichi-Sankyo, GlaxoSmithKline, Genentech-Roche, Novartis, Pierre Fabre; DSMB member for MedImmune/AstraZeneca and Novartis; stock or ownership interests from Kite Pharma, Compugen. Z.E. declares no conflicts of interest in preparing this article.

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