Background: Combination therapy using the BRAF inhibitor dabrafenib as well as the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We searched for to find out whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations.
Methods: Within this double-blind, placebo-controlled, phase 3 trial, we at random assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to get dental dabrafenib in a dose of 150 mg two times daily plus trametinib in a dose of two mg once daily (combination therapy, 438 patients) or more matched placebo tablets (432 patients) for 12 several weeks. The main finish point was relapse-free survival. Secondary finish points incorporated overall survival, distant metastasis-free survival, freedom from relapse, and safety.
Results: In a median follow-from 2.8 years, the believed 3-year rate of relapse-free survival was 58% within the combination-therapy group and 39% within the placebo group (hazard ratio for relapse or dying, .47 95% confidence interval [CI], .39 to .58 P<0.001). The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group (hazard ratio for death, 0.57 95% CI, 0.42 to 0.79 P=0.0006), but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma.
Conclusions: Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects.