Adjuvant BRAF/MEK-inhibition is safe and feasible in stage IIB/C BRAF V600-mutant melanoma

Adjuvant BRAF/MEK-targeting therapy has the potential to reduce the recurrence of stage IIB/C BRAF V600-mutant melanoma, according to results from the phase 3 Columbus AD study. The trial was ended prematurely, as simultaneous trials published similar positive effects with anti-programmed cell death protein-1 (PD-1) therapy hampered recruitment.

Stage IIB/C melanoma bears a high risk of recurrence and/or melanoma-specific death [1,2]. BRAF/MEK-directed therapy with encorafenib and binimetinib has been shown to be safe and effective in patients with unresectable stage IIIC/IV BRAF V600-mutant melanoma [3]. The Columbus AD study (NCT05270044), presented by Dr Alexander Van Akkooi (Melanoma Institute Australia, Australia), aimed to explore the efficacy and safety of the encorafenib-binimetinib combination as adjuvant treatment for patients with fully resected stage IIB/C BRAF V600-mutant melanoma [4].

The study was designed to randomly assign 815 participants to 1 year of adjuvant treatment with the encorafenib-binimetinib combination or placebo. However, during the conduct of the trial, positive results were published for adjuvant anti-PD1 therapy in participants with stage IIB/C melanoma [5,6]. “These publications complicated recruitment of participants for a placebo-controlled trial, and recruitment was terminated prematurely,” explained Dr. Van Akkooi.

Finally, 110 participants were enrolled and 1:1 randomised to the encorafenib-binimetinib combination or placebo. Recurrence-free survival at 1 year was numerically better in the encorafenib-binimetinib arm: 86% (95% CI 65–95%) versus 70% (95% CI 46–85%). Similar trends were observed for distant metastasis-free survival at 1 year, with 92% (95% CI 77–97%) versus 82% (95% CI, 55–93%) in the encorafenib-binimetinib combination or placebo arms, respectively. The combination was generally well-tolerated with a manageable toxicity profile.

“These results highlight the potential utility of BRAF/MEK-inhibition in the adjuvant setting to reduce recurrence for patients with stage IIB/C BRAF V600-mutant melanoma”, concluded Dr Van Akkooi. “Patients and physicians would love to have the choice between targeted therapy and immunotherapy in this setting.”

1. Helvind NM, et al. JAMA Dermatology 2023;159(11):1213–1222.
2. Gershenwald JE, et al. CA Cancer J Clin. 2017;67(6):472–492.
3. Schadendorf D, et al. Eur J Cancer 2024;204:114073.
4. Van Akkooij A, et al. Primary analysis of the EORTC-2139-MG/Columbus-AD trial: A randomized trial of adjuvant encorafenib and binimetinib versus placebo in high-risk stage II melanoma with a BRAF-V600E/K mutation. Abstract LBA9501, ASCO Annual Meeting 2025, May 30–June 3, Chicago, IL, USA.
5. Luke JJ, et al. J Clin Oncol 2024;42(14):1619–1624.
6. Kirkwood JM, et al. Nat Med. 2023;29(11):2835–2843.

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Posted on 30 July 2025