An adjuvant combination regimen may improve the rate of relapse-free survival by 19% in patients with stage III BRAF-mutated melanoma, according to a recent study in the New England Journal of Medicine (online September 10, 2017; doi:10.1056/NEJMoa1708539).
Patients with early-stage melanoma who undergo complete resection benefit from 5-year survival rates of over 90%. However, patients with advanced disease have much higher rates of recurrence after resection. A combination regimen involving dabrafenib plus trametinib has shown the ability to improve survival in patients with advanced BRAF-mutated metastatic melanoma, but its effectiveness as an adjuvant option has yet to be evaluated.
Georgina V Long, MB, BS, PhD, co-medical director, Melanoma Institute (Australia), and colleagues conducted a double-blind, placebo-controlled, phase III trial (COMBI-AD) to assess the effectiveness of dabrafenib plus trametinib in patients with surgically-removed, advanced BRAF-mutated melanoma. A total of 870 patients were sampled, 438 of whom received oral dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) and 432 of whom received two matched placebo tables for 12 months. The median follow-up was 2.8 years.
Results of the study showed that patients in the combination treatment arm had an estimated 3-year rate of relapse-free survival of 58% compared with 39% in patients in the placebo arm (HR, 0.47; 95% CI, 0.39-0.58; P < .001). Additionally, the 3-year overall survival rate in the combination treatment arm and the placebo arm was 86% and 77%, respectively (HR, 0.57; 95% CI, 0.42-0.79; P = .0006), though statistical significance was not met (pre-specified interim analysis boundary, P = .000019).
Authors of the study also noted that rates of distant metastasis-free survival and freedom from relapse were higher in the combination treatment arm than in the placebo arm. Furthermore, the safety profile of dabrafenib plus trametinib as an adjuvant regimen was consistent with prior data observed with the combination in patients with metastatic melanoma. Among the frequently reported adverse events were pyrexia, fatigue, nausea/vomiting, diarrhea, arthralgia, rash, and headache.
In conclusion, authors of the study support the use of dabrafenib plus trametinib as an adjuvant regimen for patients with stage III BRAF-mutated melanoma, due to its ability to improve relapse-free survival without increasing the risk of adverse events.—Zachary Bessette