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  • Title: Future of combination therapy with dabrafenib and trametinib in metastatic melanoma.
    Author: Zia Y, Chen L, Daud A.
    Journal: Expert Opin Pharmacother; 2015; 16(14):2257-63. PubMed ID: 26331795.
    Abstract:
    INTRODUCTION: Combination 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 COVERED: This 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 OPINION: Future 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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