Survival impact of adjuvant treatment in resected stage III cutaneous melanoma patients: Results from a real-life cohort study (TAMARIS).

Abstract

9576 Background: Anti-PD-1 immunotherapies and BRAF+MEK inhibitors (BRAFi/MEKi) (specifically for BRAF V600E/K-mutant melanoma) have been shown to improve recurrence-free survival (RFS) in patients (pts) with resected stage III metastatic melanoma in phase III trials. However, none of these studies has demonstrated a significant improvement in overall survival (OS). Notably, adjuvant BRAFi/MEKi therapy has shown better OS only in the BRAF V600E subgroup of patients. In this context, we evaluated the real-world impact of adjuvant therapies on OS. Methods: TAMARIS is a national multicenter retrospective study designed to evaluate the efficacy of adjuvant treatment (anti-PD-1 or BRAFi/MEKi) in pts with resected AJCC 8 th edition stage III melanoma using data from the French RIC-Mel prospective database. The primary endpoint was OS analyzed using the Kaplan-Meier method, comparing pts who received adjuvant treatment (adjuvant group) within 3 months of surgery to those who did not (control group). Demographic and clinical characteristics were compared using chi-square analyses. Secondary endpoints included OS in specific subgroups and RFS. Results: A total of 1,172 pts (median age: 65 years [IQR: 53–74]) with resected stage III melanoma were included between 2018 and 2023. Among them, 796 pts (68%) received adjuvant treatment with anti-PD-1 (n=676) or BRAFi/MEKi (n=120). The median treatment duration was 10.8 months (IQR: 5.6–11.9). Most pts had a history of SSM (54%) with a median Breslow thickness of 2.8 mm [range, 0-47] and stage IIIB (31%) or IIIC disease (49%). Surgical interventions for metastases prior to adjuvant treatment included lymph node dissection in 53% of cases, sentinel lymph node biopsy in 38%, and cutaneous metastasis resection in 8%. Pts in the control group were older (median age: 69.7 vs. 63.0 years, p < 0.0001). The median follow-up was 30.4 months (IQR: 16.7-43.3). OS was significantly longer in the adjuvant group compared to the control group (HR: 0.617; 95% CI: 0.474-0.802; p = 0.0003), with a 2-year OS of 90% (95% CI: 88-92) in the adjuvant group versus 79% (95% CI: 74-83) in the control group. There was a trend toward better OS with BRAFi/MEKi compared to anti-PD-1 (HR: 0.569; 95% CI: 0.312-1.037; p = 0.065). Subgroup analyses demonstrated a significant positive impact of adjuvant treatment on OS across most subgroups, except for pts aged ≤75 years, those with stage IIIA disease, primary melanomas with a Breslow thickness <2.8 mm, or without ulceration. RFS also favored the adjuvant group (HR: 0.545; 95% CI: 0.458-0.649; p < 0.0001), with a 2-year RFS of 67% (95% CI: 63-70) and 45% (95% CI: 40-50) in the control group. Conclusions: Adjuvant treatment appears to provide an OS benefit in patients with resected stage III melanoma in real-world settings. Further research is required as age-related differences may influence prognosis.