Dabrafenib plus trametinib adjuvant therapy significantly lowered the risk of recurrence in patients with BRAFV600E or V600K –mutation positive stage III melanoma compared with placebo, according to a study published in The New England Journal of Medicine.1
Complete resection is the standard therapy for patients with early-stage melanoma, leading to 5-year survival rates of 98% for stage I and 90% for stage II. Patients with advanced melanoma, however, have much higher rates of recurrence even after resection, as there is regional involvement at diagnosis.
For the phase 3 COMBI-AD study (ClinicalTrials.gov Identifier: NCT01682083), investigators randomly assigned 870 patients with advanced melanoma with BRAFV600E/K mutations who had undergone complete resection to receive oral trametinib 2 mg once daily and dabrafenib 150 mg twice daily vs placebo for 1 year. The median follow-up was 2.8 years.
Patients who received adjuvant therapy with dabrafenib and trametinib had an estimated 3-year rate of relapse-free survival of 58% vs 39% in patients who received placebo (hazard ratio [HR], 0.47; 95% CI, 0.39-0.58; P < .001).
The 3-year overall survival rate in the combination therapy arm and placebo arm was 86% and 77%, respectively (HR, 0.57; 95% CI, 0.42-0.79; P = .0006), but did not meet the pre-specified interim analysis boundary of P = .000019 to meet statistical significance.
The combination group also had higher rates distant metastasis-free survival.
Frequently reported adverse events (AEs) included pyrexia, fatigue, nausea/vomiting, diarrhea, arthralgia, rash, and headache, and were consistent with reported rates of AEs from previous studies.
- Long GV, Hauschild A, Santinami M, et al. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med. 2017 Sep 10. doi: 10.1056/NEJMoa1708539 [Epub ahead of print]