Optimal Adjuvant Therapy Selection for Chinese BRAF V600-Mutant Stage III Melanoma: A Multicenter Efficacy Comparison of Targeted Agents, Immunotherapy, and Combinatorial Strategies

Abstract

While adjuvant immunotherapy and BRAF/MEK inhibitors improve the outcomes for BRAF V600-mutant stage III melanoma, comparisons of long-term survival and safety of these therapeutic modalities are currently lacking in Chinese patients. We retrospectively analyzed data from patients with resected stage III BRAF V600-mutant melanoma who received adjuvant therapy between June 2013 and December 2023 across three centers in China. Note that 122 patients were included and categorized into interferon (n = 25), aPD-1 (n = 18), D/T (n = 62), and BRAFi/aPD-1 (n = 17) cohorts. The D/T group demonstrated a significantly longer median RFS compared to the interferon and aPD-1group (22.7 vs. 11.9 months, p = 0.005; vs. 12.5 months, p < 0.001). Similar results were obtained by restricted-mean-survival-time model. Patients who continued D/T beyond 1 year exhibited significantly improved RFS and DMFS compared to those who discontinued at 1 year duration (NR vs. 22.0 months, p = 0.048; NR vs. 22.5 months, p = 0.026). NOTCH4 and IL7R mutations may serve as prognostic and predictive biomarkers for long-term survival and targeted-immunotherapy efficacy, respectively. Adjuvant therapy with D/T may represent the most effective treatment strategy for Chinese patients with stage III melanoma harboring BRAF V600 mutations. A combination of BRAF-targeted therapy and aPD-1 immunotherapy provided comparable efficacy and may be an alternative for a specific patient.

Keywords

adjuvant therapy / BRAF V600 mutation / melanoma / targeted therapy / target-immune combination therapy

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