The BRAF V600E mutation is found in approximately 50% of cutaneous malignant melanomas. The targeted therapy combination approved for BRAF-mutant metastatic melanoma uses:

• A BRAF inhibitor alone (vemurafenib)
• B BRAF inhibitor + MEK inhibitor (e.g., dabrafenib + trametinib) ✓
• C PD-1 checkpoint inhibitor alone (nivolumab)
• D CTLA-4 inhibitor alone (ipilimumab)

Explanation

BRAF V600E mutation activates the MAPK/ERK signalling pathway, promoting uncontrolled melanoma cell proliferation. BRAF inhibitor monotherapy (vemurafenib) leads to acquired resistance within 6–7 months via MEK pathway reactivation. Combining a BRAF inhibitor (vemurafenib, dabrafenib, encorafenib) with a MEK inhibitor (cobimetinib, trametinib, binimetinib) overcomes this resistance mechanism and significantly improves PFS and OS compared to monotherapy. Pembrolizumab/nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) are immunotherapy options for both BRAF-mutant and wild-type melanoma.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

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Written and medically reviewed by the StethoPrep medical team.