Addition of anti-PD-1 immunotherapy to BRAF inhibitor-based targeted therapy improves real-world survival and delays brain metastases in patients with BRAF^V600-mutant advanced melanoma: a multicenter cohort study

Abstract

Anti-PD-1 immunotherapy and targeted therapy (TT) represent two major therapeutic modalities for BRAF^V600-mutant advanced melanoma, but the efficacy of combination therapy in Asian populations remains unknown. Asian melanoma patients differ significantly from Caucasians in tissue subtypes, pathogenesis and response to treatment. We retrospectively analyzed data of BRAF^V600-mutant advanced melanoma patients treated with first-line vemurafenib (V) ± anti-PD-1 or dabrafenib+trametinib (D+T) ± anti-PD-1 between 2014 and 2023 from three centers in China. 178 patients were included, with V (n = 45), D+T (n = 51), V+anti-PD-1 (n = 39) and D+T+anti-PD-1 (n = 43). The median PFS (21.9 vs. 11.1 months, p < 0.001), OS (NR vs. 32.6 months, p = 0.027), and DoR (20.0 vs. 8.4 months, p = 0.002) were significantly prolonged with D+T+anti-PD-1 versus D+T. Addition of anti-PD-1 to V also significantly prolonged PFS, OS, and DoR (p < 0.001). V+anti-PD-1 was superior to D+T in terms of PFS (15.0 vs. 11.1 months, p = 0.007) and DoR (18.0 vs. 8.4 months, p = 0.013), and was comparable to D+T+anti-PD-1. Addition of anti-PD-1 to BRAF inhibitor-based TT was associated with lower incidence of brain metastases (p = 0.032). Addition of anti-PD-1 to BRAF inhibitor-based TT appears to be a safe and effective treatment option, conferring a survival benefit and delaying the onset brain metastases in patients with BRAF^V600-mutant advanced melanoma.

Keywords

anti-PD-1 / BRAF / brain metastasis / melanoma / targeted therapy

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