Journal
EXPERT OPINION ON PHARMACOTHERAPY
Volume 16, Issue 9, Pages 1285-1297Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14656566.2015.1044971
Keywords
binimetinib; BRAF; cobimetinib; dabrafenib; MAPK; MEK; melanoma; NRAS; trametinib; vemurafenib
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Introduction: BRAF inhibition alone has achieved unprecedented efficacy results in patients affected by BRAF-mutated advanced melanoma. Since these findings, it was postulated that dual inhibition of BRAF and other components of the RAS/RAF/MEK/ERK MAPK pathway (such as MEK) would be superior to BRAF inhibition as monotherapy. A series of recent clinical trials have confirmed this hypothesis. Areas covered: In this article, the biological rationale for both single and concomitant inhibitions of the MAPK pathway in BRAF mutant melanoma is provided. Moreover, available clinical data on the efficacy and toxicity of BRAF and MEK inhibition as single agents and in combination are extensively reviewed. Expert opinion: Dual BRAF and MEK inhibition in advanced BRAF-mutated melanoma is superior to single inhibition in terms of efficacy without significant increase in toxicity. Therefore, BRAF plus MEK inhibition is expected to supersede single-agent BRAF inhibition in these patients in the near future.
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