TY - JOUR
T1 - primary analysis of the RANDOMIZED eortc-2139/columbus-ad trial
T2 - Adjuvant encorafenib and binimetinib versus placebo in high-risk stage II BRAF-V600E/K melanoma
AU - van Akkooi, Alexander C.J.
AU - Kicinski, Michal
AU - Govaerts, Anne Sophie
AU - Hauschild, Axel
AU - Rutkowski, Piotr
AU - Arenberger, Petr
AU - Ascierto, Paolo A.
AU - Tomczak, Piotr
AU - Quereux, Gaëlle
AU - De Galitiis, Federica
AU - Dutriaux, Caroline
AU - Gebhardt, Christoffer
AU - Kapiteijn, Ellen
AU - Machet, Laurent
AU - Berciano, Miguel G.A.
AU - Del Vecchio, Michele
AU - Jalving, Mathilde
AU - Jouary, Thomas
AU - Krajsova, Ivana
AU - Matkovic, Suzana
AU - Merelli, Barbara
AU - Mortier, Laurent
AU - Pagès-Laurent, Pages Laurent Cecile
AU - Palmieri, Giuseppe
AU - Pracht, Marc
AU - Vantuchova, Yvetta
AU - Massi, Daniela
AU - Elaut, Nathalie
AU - de Schaetzen, Gaetan
AU - Nuyens, Sarah
AU - Jha, Nitish
AU - Klauck, Isabelle
AU - Sansas, Benoît
AU - Vedovato, Jean Claude
AU - Lorigan, Paul C.
AU - Long, Georgina V.
AU - Eggermont, Alexander M.M.
AU - Mandala, Mario
N1 - Publisher Copyright:
Copyright © 2026. Published by Elsevier Ltd.
PY - 2026/9/9
Y1 - 2026/9/9
N2 - 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.
AB - 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.
KW - Adjuvant
KW - BRAF
KW - Binimetinib
KW - Encorafenib
KW - MEK
KW - Melanoma
KW - Stage II Melanoma
UR - https://www.scopus.com/pages/publications/105045632111
U2 - 10.1016/j.ejca.2026.116951
DO - 10.1016/j.ejca.2026.116951
M3 - Article
AN - SCOPUS:105045632111
SN - 0959-8049
VL - 245
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 116951
ER -