• Expert Opin Pharmacother · Jan 2015

    Review

    Future of combination therapy with dabrafenib and trametinib in metastatic melanoma.

    • Yasaman Zia, Lawrence Chen, and Adil Daud.
    • a 1 UCSF Helen Diller Comprehensive Cancer Center , 1600 Divisadero Street, Room B708, San Francisco, CA 94115, USA +1 20 24 89 19 86 ; +1 41 55 14 69 69 ; yaszia@gmail.com.
    • Expert Opin Pharmacother. 2015 Jan 1; 16 (14): 2257-63.

    IntroductionCombination therapy with BRAF and MEK inhibitors is a recommended treatment strategy for metastatic melanoma patients with BRAF(V600) mutations. This treatment provides significant response rates and little added toxicity, with relatively improved survival outcomes compared to RAF/MEK inhibitor monotherapy and chemotherapy.Areas CoveredThis review covers the pharmacology, efficacy, and toxicity data derived from clinical studies of dabrafenib, trametinib , and the combination thereof. The major downfall of combiDT is the limited durability of response, which is largely due to acquired resistance in the MAPK pathway.Expert OpinionFuture directions of combiDT concentrate on further combinations with immunotherapy or other targeted inhibitors, referred to triple-agent therapy, which may be essential to improving durability of responses and overcoming resistance.

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