Which BRAF status is contraindicated for binimetinib and encorafenib combination therapy?

• A. Wild-type BRAF melanoma
• B. BRAF V600E melanoma
• C. BRAF V600K melanoma
• D. BRAF V600M melanoma

Answer: (B)

The main idea is that this binimetinib plus encorafenib combo is meant for melanomas driven by activating BRAF mutations, especially those at V600E or V600K. Encorafenib blocks the mutant BRAF signaling, and binimetinib adds a MEK inhibitor to shut down the pathway further and reduce resistance. In tumors that are BRAF wild-type (no activating BRAF mutation), using a BRAF inhibitor can paradoxically activate the MAPK pathway in surrounding cells, potentially promoting tumor growth instead of inhibiting it, and there’s no meaningful clinical benefit. That’s why wild-type BRAF melanoma is not treated with this combination. Some non-V600 BRAF mutations exist, and responses can vary, but the core contraindication is the absence of a BRAF activating mutation.