A 55-year-old patient has a nodular malignant melanoma. The Breslow thickness is 2.1mm and Clark level IV. Sentinel lymph node biopsy is positive. Molecular testing shows BRAF V600E mutation. The targeted therapy combination that is standard of care is:

• A Vemurafenib alone (BRAF inhibitor)
• B Ipilimumab (anti-CTLA4) alone
• C Nivolumab + pembrolizumab (dual checkpoint blockade)
• D Dabrafenib + trametinib (BRAF + MEK inhibitors) ✓

Explanation

For BRAF V600E-mutated metastatic melanoma, the standard targeted therapy is dual BRAF inhibitor + MEK inhibitor combination: dabrafenib + trametinib, or vemurafenib + cobimetinib. The combination delays resistance (which develops quickly with BRAF inhibitor monotherapy via MEK pathway bypass) and reduces cutaneous squamous cell carcinoma paradoxical activation. BRAF V600E is present in ~50% of cutaneous melanomas; testing is mandatory. Anti-PD1 immunotherapy (pembrolizumab/nivolumab) is the alternative for BRAF wild-type or as first-line.

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

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Written and medically reviewed by the StethoPrep medical team.