Immune checkpoint inhibitors in advanced cutaneous melanoma: a systematic review and meta-analysis of efficacy and review of characteristics

Objectives: Immune checkpoint inhibitors (ICIs) are one of the most promising approaches toward advanced melanoma. Here, we aimed to perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of all studied ICIs.Methods: We conducted a comprehensive search to identify the relevant publications (PROSPERO registration ID: CRD42023470649). Then we performed a meta-analysis to evaluate the efficacy of different ICIs for metastatic melanoma. We used Cochrane's tool to assess the quality of studies. The outcome measures were overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS).Results: Twenty reports of RCTs entered our systematic review, 18 of which were included in our data analysis. ICIs showed improved survival compared with control group (hazard ratio (HR) = 0.57; 95% CI: 0.43-0.71; P<0.001). Using a meta-regression, we found a significant relation between patients' mean age and their OS (P<0.001, R-2 = 100.00%). Also, our analysis revealed greater HR for CTLA-4 inhibitors than PD-1/PD-L1 inhibitors (HR = 0.71, 95%CI: 0.63-0.79, P<0.001 vs. HR = 0.63, 95%CI: 0.46-0.79, P<0.001). The effect sizes of different types of PD-1/PD-L1 inhibitors were comparable.Conclusion: Our results suggest that ICI-based immunotherapy is associated with enhanced OS, PFS, and RFS (P < 0.001) and will assist clinicians in choosing the optimal approach toward treating metastatic melanoma.