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Comparative Study
. 2025 Jun;132(12):1124-1130.
doi: 10.1038/s41416-025-03021-5. Epub 2025 Apr 15.

Adjuvant BRAF/MEK versus anti-PD-1 in BRAF-mutant melanoma: a propensity score matched survival analysis

M Bloem  1   2   3 , M M de Meza  4   5 , A J M van den Eertwegh  6 , M J B Aarts  7 , F W P J van den Berkmortel  8 , C U Blank  9 , W A M Blokx  10 , M J Boers-Sonderen  11 , J J Bonenkamp  12 , C D M Boreel  13   14 , J W B de Groot  15 , J B A G Haanen  9 , G A P Hospers  16 , E Kapiteijn  17 , O J van Not  18 , D Piersma  19 , B Rikhof  20 , A M Stevense-den Boer  21 , A A M van der Veldt  22 , G Vreugdenhil  23 , K P M Suijkerbuijk  14 , M W J M Wouters  13   4   5
Affiliations
Comparative Study

Adjuvant BRAF/MEK versus anti-PD-1 in BRAF-mutant melanoma: a propensity score matched survival analysis

M Bloem et al. Br J Cancer. 2025 Jun.

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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Conflict of interest statement

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.

References

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