Abstract
Background
Adjuvant BRAF/MEK inhibitors (BRAF/MEK) and anti-PD-1 therapy have become the standard care in resected stage III/IV melanoma. A head-to-head clinical trial comparison is lacking.
Methods
All stage III BRAF-mutant melanoma patients who received adjuvant BRAF/MEK or anti-PD-1 (2018-2022) were included from the Dutch Melanoma Treatment Registry. Propensity score matching (PSM) was used to compare 1- and 2-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS), and toxicity rates.
Findings
Among 952 patients (226 BRAF/MEK and 726 anti-PD-1), BRAF/MEK-treated patients had lower disease stages (16·4% versus 9·9% stage IIIA; p < 0·01) and more often comorbidities (75·2% versus 63·4%; p < 0·01). Median follow-up was 29 months. PSM created two similar groups of 223 patients. RFS, DMFS, and OS were not significantly different before and after PSM. Two-year RFS was 62% (95% CI 55–71) for BRAF/MEK and 65% (95% CI 58–72) for anti-PD-1; 2-year DMFS was 81% (95% CI 74–87) versus 81% (95% CI 75–86); 2-year OS was 86% (95% CI 81–92) versus 89% (95% CI 85–94), respectively. Grade ≥ 3 toxicity was reported in 11·7% (BRAF/MEK) and 13·4% (anti-PD-1).
Conclusion
After PSM, no significant differences in outcomes were observed between adjuvant anti-PD-1 and BRAF/MEK-treated patients with stage III BRAF-mutant melanoma.
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Data availability
Research data is available upon reasonable request.
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Funding
The author(s) received no specific funding for this work. This study was supported by the Dutch Melanoma Treatment Registry (DMTR); the Dutch Institute for Clinical Auditing foundation received a start-up grant from governmental organization the Netherlands Organization for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019, Novartis stopped funding in 2023, and Pierre Fabre started funding the DMTR in 2019.
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Contributions
Bloem: Conceptualization, data curation, formal analysis, methodology, investigation, project administration, writing—original draft, and writing—review & editing. De Meza: Conceptualization, methodology, project administration, writing—original draft, and writing—review & editing. van den Eertwegh: Conceptualization, investigation, methodology, project administration, supervision, writing—review & editing. Aarts: Investigation, project administration, writing—review & editing. van den Berkmortel: Investigation, project administration, writing—review & editing. Blank: Investigation, project administration, writing—review & editing. Blokx: Investigation, project administration, writing—review & editing. Boers-Sonderen: Investigation, project administration, writing—review & editing. Bonenkamp: Investigation, project administration, writing—review & editing. Boreel: Investigation, project administration, writing—review & editing. de Groot: Investigation, project administration, writing—review & editing. Haanen: Investigation, project administration, writing—review & editing. Hospers: Investigation, project administration, writing—review & editing. Kapiteijn: Investigation, project administration, writing—review & editing. van Not.: Investigation, project administration, writing—review & editing. Piersma: Investigation, project administration, writing—review & editing. Rikhof: Investigation, project administration, writing—review & editing. Stevense-den Boer: Investigation, project administration, writing—review & editing. van der Veldt: Investigation, project administration, writing—review & editing. Vreugdenhil: Investigation, project administration, writing—review & editing. Suijkerbuijk: Conceptualization, investigation, methodology, project administration, supervision, writing—review & editing. Wouters: Conceptualization, investigation, methodology, project administration, supervision, writing—review & editing.
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Competing interests
AE participates in the Advisory Boards of Bristol-Myers Squibb, MSD Oncology, Ipsen, Pierre Fabre, Janssen Cilag BV. All fees were paid to the institution. GH has received grants from Seerave and Bristol-Myers Squibb, paid to the institution. GH participates in the Advisory Boards of Bristol-Myers Squibb, Roche, MSD, Novartis, Sanofi, Pierre Fabre, and Amgen. All fees were paid to the institution. KS has received grants from AbbVie, Novartis, Genmab, Philips, and Pierre Fabre, and participates in the Advisory Boards of AbbVie and Sairopa. All fees were paid to the institution. MA has received personal payment for the GUCS review; a national, online presentation “Highlight medical oncologie GU” in the Netherlands. MA received personal support from ASCO (2022) to attend the meeting. MA participated in the Advisory Boards of Amgen, Bristol Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Astellas, Bayer, and received a research grant from Merck-Pfizer. All fees were paid personally. AV participates in the Advisory Boards of Bristol-Myers Squibb, MSD, Ipsen, Eisai, Roche, Novartus, Sanofi, and Pfizer. All fees were paid to the institution. DP has received payment from Novartis for education about melanoma for new employees and from BMS for case writing for educational purposes. DP participates in the Advisory Boards of Peirre Fabre.
Ethics approval
The medical ethical committee considered the DMTR not subject to the Medical Research Involving Human Subjects Act under Dutch regulations since all data is anonymized, eliminating the need for informed consent. The study was performed in accordance with the Declaration of Helsinki.
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Bloem, M., de Meza, M.M., van den Eertwegh, A.J.M. et al. Adjuvant BRAF/MEK versus anti-PD-1 in BRAF-mutant melanoma: a propensity score matched survival analysis. Br J Cancer 132, 1124–1130 (2025). https://doi.org/10.1038/s41416-025-03021-5
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DOI: https://doi.org/10.1038/s41416-025-03021-5
