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

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.