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Combination therapy with signal transduction inhibitors

Source: Melanoma Treatment (PDQ®)–Health Professional Version, National Cancer Institute.

Source updated: May 2, 2025 · Captured 2026-09-09.

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Context: Treatment of Unresectable Stage III, Stage IV, and Recurrent Melanoma / Treatment Options for Unresectable Stage III, Stage IV, and Recurrent Melanoma / Signal transduction inhibitors

Results from phase III trials comparing three different combinations of BRAF-MEK inhibitors with BRAF inhibitor monotherapy have consistently shown that combination therapy is superior to BRAF monotherapy.

Secondary resistance to BRAF inhibitor monotherapy in patients with BRAF V600 pathogenic variants may be associated with reactivation of the MAPK pathway. Therefore, combinations of signal transduction inhibitors that block different sites in the same pathway or sites in multiple pathways are an active area of research.

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BRAF inhibitor plus MEK inhibitors →Dabrafenib plus trametinib →Vemurafenib plus cobimetinib →Encorafenib plus binimetinib →

Preserved source evidence · Not medical advice