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.

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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.

Reference

  1. 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]