Efficacy of immune checkpoint inhibitors in advanced mucosal melanoma: A systematic review and meta-analysis

Introduction: Advanced mucosal melanoma (aMM) is commonly treated with immune checkpoint inhibitors (ICIs) including anti-CTLA-4 and anti-PD-1 therapies alone or in combination. Although consensus guidelines suggest combination treatment for advanced mucosal melanoma, evidence is limited as these are based on small studies of heterogeneous patient populations and thus quantification of their benefit are difficult to establish. Methods: A systemic review and meta-analysis was conducted to benchmark efficacy of ICIs in treating aMM (PROSPERO registration CRD42023422856). Outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse event (AE) incidence were pooled using the inverse-variance method and random effects models. Results: 29 studies encompassing 2022 patients were included for analysis. Combination anti-CTLA-4 and anti-PD-1 therapy resulted in modestly superior ORR, median OS and PFS outcomes at 31.9 %, 19.1 months and 5.0 months; followed by anti-PD-1 monotherapy at 24.8 %, 14.6 months and 3.8 months; and finally anti-CTLA-4 monotherapy at 10.6 %, 8.1 months and 3.2 months (P < 0.001 for all). Grade 3 or higher AEs occurred in 50.3 %, 14.5 % and 23.0 % of treatment cohorts, respectively. Conclusion: Combination ICI treatment is associated with modestly higher activity than monotherapy in aMM, at the cost of substantially higher AEs. Treatment selection should involve individual risk-benefit considerations and shared decision making.