LAUSR

Patients with stage III melanoma typically undergo surgery, followed by consideration for adjuvant therapy; however, only 30–50% of these patients are likely to survive >5 years after diagnosis. Now, the findings of a phase II trial demonstrate that combined BRAF plus MEK inhibition in both the neoadjuvant and adjuvant setting improves the outcomes of patients undergoing surgery for stage III BRAF-mutant or BRAF-mutant melanoma. In the phase II study, investigators randomized a total of 21 patients in a 2:1 ratio to receive either the standard-of-care approach (surgery, followed by consideration of adjuvant therapy) or surgery with neoadjuvant and adjuvant use of the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib. Notably, this trial was closed after a median follow-up duration of 18.6 months, owing to the emergence of significant differences in the primary outcome (event-free survival; EFS): patients in the dabrafenib plus trametinib group had a median EFS duration of 19.7 months versus 2.9 months in the standard-of-care group (HR 0.016, 95% CI 0.00012–0.14; P < 0.0001). Virtually all patients in the dabrafenib plus trametinib group had grade 1–2 toxicities, such as chills and headaches (both occurred in 92% of patients). The most common grade ≥3 toxicity was grade 3 diarrhoea in two patients (15%); however, this profile might be somewhat misleading as four patients in the dabrafenib plus trametinib group discontinued treatment owing to adverse events during the adjuvant phase and nearly all patients required dose reductions. These findings demonstrate the efficacy of neoadjuvant plus adjuvant targeted therapies compared with the current approach. However, further research will be required to determine the necessity of neoadjuvant treatment: adjuvant use of dabrafenib plus trametinib has also provided promising outcomes in this setting. Peter Sidaway R E S E A R C H H I G H L I G H T S