A 12-month treatment regimen of adjuvant therapy with dabrafenib plus trametinib was associated with a significantly greater prolonged survival without relapse or distant metastasis compared with placebo over 5 years in patients with stage 3 melanoma with BRAF V600E or V600K mutations, according to study findings published in the New England Journal of Medicine.

Findings from this study were based on an analysis of 5-year follow-up data from the phase 3 COMBI-AD trial. In this analysis, a total of 870 patients with resected stage 3 melanoma with BRAF V600E or V600K mutations received either 150 mg dabrafenib twice daily plus 2 mg trametinib once daily (n=435) or 2 matched placebos (n=432) over 12 months.

Relapse-free survival (RFS) comprised the primary endpoint; however, the analysis of the 5-year results focused on both RFS and survival without distant metastasis at the site of the first relapse.

The minimum follow-up duration was 59 months; the median follow-up per patient group was 60 months in patients who received combination therapy and 58 months in the placebo arm.


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A greater percentage of patients in the adjuvant therapy arm were alive without relapse at 5 years was (52%; 95% CI, 48-58) compared with patients randomly assigned to placebo (36%; 95% CI, 32-41) (hazard ratio [HR], 0.51; 95% CI, 0.42-0.61). In addition, a greater percentage of patients treated with dabrafenib plus trametinib were alive without distant metastasis compared with those treated with placebo (65% [95% CI, 61-71] vs 54% [95% CI, 49-60], respectively; HR, 0.55; 95% CI, 0.44-0.70). Duration of RFS was also longer with combination therapy compared with placebo across all stage 3 melanoma substages.

There were no clinically meaningful differences between groups in terms of either the incidence or severity of serious adverse events (AEs) during follow up. The investigators noted that most AEs associated with the combination therapy were transient and had resolved following treatment discontinuation or interruption.

As the researchers were unable to assess overall survival (OS) in this cohort, they concluded that “effect of adjuvant therapy with dabrafenib plus trametinib on long-term overall survival remains to be determined.”

Disclosure: This clinical trial was supported by GlaxoSmithKline and Novartis. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Dummer R, Hauschild A, Santinami M, et al. Five-year analysis of adjuvant dabrafenib plus trametinib in stage III melanoma. N Engl J Med. 2020;383(12):1139-1148. doi:10.1056/NEJMoa2005493