Skin: Adjuvant systemic therapy stage III and BRAF testing

Why D is correct

COMBI-AD randomised patients with completely resected stage III BRAF V600E/V600K melanoma to 12 months of dabrafenib plus trametinib or placebo, showing a 3-year relapse-free survival of 58% versus 39% (hazard ratio 0.47). For a fit patient with resected stage III BRAF V600E melanoma, 12 months of combination BRAF/MEK inhibition is the evidence-based adjuvant choice.

And why the others are not

• AIncorrect: single-agent BRAF inhibition is not the adjuvant standard; combination BRAF/MEK inhibition (dabrafenib plus trametinib) for 12 months is supported, not 5 years of vemurafenib monotherapy.
• BIncorrect: dacarbazine has no established adjuvant role and was not the comparator that demonstrated benefit in this setting.
• CIncorrect: COMBI-AD demonstrated a clear relapse-free survival benefit over placebo, so observation alone is not the best supported option for fit BRAF-mutant patients.
• EIncorrect: adjuvant interferon has largely been superseded by targeted and immune checkpoint therapy and does not match the COMBI-AD benefit.

Source COMBI-AD - Adjuvant dabrafenib plus trametinib in resected stage III BRAF-mutated melanoma — Long GV, Hauschild A, Santinami M, et al. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med. 2017;377(19):1813-1823.