Adjuvant Therapy and Outcomes in Patients with Stage III BRAF-Mutated Cutaneous Melanoma: Real-World Data

Adjuvant therapy for BRAF-mutated stage III melanoma patients includes targeted therapy (dabrafenib + trametinib) and anti-PD-1 immunotherapy (pembrolizumab or nivolumab). Direct comparative studies are lacking, and data are limited to retrospective analyses. The aim of our study was to compare the efficacy of these regimens in a Russian patient population in real-world clinical practice among patients with BRAF mutations. Material and methods. A single-center retrospective study was conducted. We included patients with stage III melanoma with a BRAF mutation who received adjuvant therapy between January 2019 and December 2022. All included patients were treated or consulted at the N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health. The primary endpoint was relapse-free survival (RFS), and secondary endpoints included overall survival (OS), progression-free survival (PFS) for patients who experienced progression, the rate of distant metastasis and toxicity. Results. The study included 246 patients: 107 received targeted therapy (TT), 122 received immunotherapy (IT), and 17 were under observation (this group was not analyzed). The median follow-up was 38.5 months. The median RFS was 44 months in the TT group and 39 months in the IT group (HR 0.79, 95% CI 0.55–1.15, p = 0.22). The one- and two-year RFS rates were 88.8% (95% CI 83–95) and 63.1% (95% CI 54.5–73) in the TT group and 61.5% (95% CI 53.4–70.7) and 54.1% (95% CI 45.9–63.7) in the IT group respectively. The median OS was not reached in either group (HR 0.59, 95% CI 0.28–1.25, p = 0.169). The one- and two-year OS rates were 100% (95% CI 100–100) and 95.2% (95% CI 91.2–99.4) in the TT group and 94.3% (95% CI 90.2–98.5) and 88.5% (95% CI 83–94.3) in the IT group respectively. No new or unexpected toxicity was reported in either treatment group. Progression occurred in 117 patients: 51 in the TT group (10 during adjuvant therapy and 41 after its completion) and 66 in the IT group (41 during adjuvant therapy and 25 after its completion). The rate of distant metastasis was higher in the TT group (68.6 vs 53%, p = 0.08). After progression, patients more frequently received alternative therapies. The median PFS was 9 months in the TT group and 15 months in the IT group (HR 1.23, 95% CI 0.74–2.05, p = 0.414). Conclusions. Targeted therapy demonstrated a numerical advantage in RFS and OS compared to immunotherapy, although these differences were not statistically significant. Targeted therapy may be more effective in preventing early relapses. The absence of statistically significant differences needs longer follow-up to assess long-term outcomes. The retrospective nature of the study and the lack of randomization limit the reliability of the conclusions.