primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial: Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma
In brief
Adjuvant encorafenib-binimetinib lifts 12-month RFS to 86% vs 70% placebo
In a randomized trial of 110 patients with resected stage IIB/IIC BRAF-mutated melanoma, one year of oral encorafenib plus binimetinib achieved an 86% recurrence-free survival at 12 months, compared with 70% for placebo-a 16-percentage-point gain. Grade 3 or higher adverse events occurred in one-quarter of treated patients, and a third stopped therapy permanently, highlighting a modest benefit balanced by notable toxicity.
- Journal
- European journal of cancer (Oxford, England : 1990) (Q1)
- Published
- 21 July 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Alexander Cj van Akkooi, Michal Kicinski, Anne-Sophie Govaerts, Axel Hauschild, Piotr Rutkowski, Petr Arenberger, et al.
- PMID
- 42501621
- DOI
- 10.1016/j.ejca.2026.116951
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 27 July 2026): Adjuvant encorafenib + binimetinib vs placebo in BRAF‑mutated melanoma
Abstract
PURPOSE: Stage IIB/IIC melanoma has a high risk of recurrence after resection. Combined BRAF/MEK inhibitor therapy showed benefit in resected high-risk stage III and advanced melanoma. The objective of this study was to investigate its role in stage IIB/IIC. METHODS: Adult patients with resected stage IIB/IIC cutaneous melanoma which had a BRAF V600E/K mutation were randomized 1:1 to receive encorafenib (enco) 450 mg QD + binimetinib (bini) 45 mg BID orally for one year or placebo. The study planned to randomize 815 patients and was designed to demonstrate superiority regarding recurrence-free survival (RFS). Following a premature termination of accrual, the study was amended with safety as the primary endpoint and RFS as secondary endpoint. RESULTS: Between June 9, 2022, and October 9, 2023, 339 patients were screened for a BRAF mutation and 110 randomized. Data cutoff was 19 Nov. 2024, after the last patient discontinued study participation. Among randomized patients, 87 (79%) had a BRAF V600E mutation, and 39 (35%) AJCC8 stage IIC. Median follow-up was 12 and 7 months for enco/bini and placebo arms, respectively. Among 54 patients who initiated enco + bini, grade ≥ 3 treatment-related adverse events (AE) occurred in 13 (24%) patients, and 18 (33%) patients had an AE leading to permanent treatment discontinuation. RFS at 12 months was 86% (95% CI: 65-95%) in the enco + bini and 70% (95% CI: 46-85%) in the placebo arm, distant metastasis-free survival at 12 months was 92% (95% CI: 77-97%) for enco + bini and 82% (95% CI: 55-93%) for placebo. CONCLUSION: EORTC 2139 - Columbus-AD demonstrated a consistent and manageable safety profile and encouraging efficacy results for the combination of enco and bini in resected stage IIB/C BRAF V600E/K-mutated cutaneous melanomas.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.