Final results of the multinational phase 3 COMBI-AD trial of adjuvant dabrafenib plus trametinib in BRAF V600-mutated stage III melanoma

The multinational phase 3 COMBI-AD trial randomized patients after resection of BRAF V600-mutated stage III to 12 months of adjuvant dabrafenib plus trametinib or two matched placebos. Final results of the trial have now been published. The median duration of follow-up was 8.33 years in the combination therapy group and 6.87 years in the placebo group. Estimates for overall survival favored the combination over placebo, although the benefit was not significant (HR 0.80; 95% CI 0.62-1.01). Among the patients with melanoma with BRAF V600E mutation the OS benefit with the combination versus placebo was significant (HR 0.75; 95% CI 0.58-0.96). Relapse-free survival (HR 0.52; 95% CI 0.43-0.63) and distant metastasis-free survival (0.56; 0.44-0.71) favored the combination over placebo. The authors conclude that after nearly 10 years of follow-up, adjuvant therapy with dabrafenib plus trametinib was associated with better relapse-free survival and distant metastasis-free survival than placebo among patients with resected stage III melanoma. The risk of death was 20% lower with the combination than with placebo, but this benefit was not significant.