Comparative efficacy and safety of immune checkpoint inhibitors for unresectable advanced melanoma: A systematic review and network meta-analysis

Background: Immune checkpoint inhibitors (ICIs) have entered the treatment paradigm for unresectable advanced melanoma, but there is a lack of evidence regarding its relative efficacy and safety. This study aim to compare the efficacy and safety of ICIs in patients with advanced unresectable melanoma.Methods: Studies included randomized clinical trials (RCTs) that compared ICIs, or combination therapy of ICIs, or with chemotherapy drugs, different ICIs, or one of the ICIs at different dosing schedules. Random-effects models of Bayesian network meta-analysis were performed following the PRISMA reporting guideline. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events. PROSPERO: CRD42021229086.Results: Twenty-four RCTs with 18 different treatment regimens for advanced melanoma involving 10,090 pa-tients were included. Overall, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg treatment regimen were associated with the highest beneficial effect on OS, PFS, and DCR. Closely followed by nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, and nivolumab plus relatlimab treatment regimens. However, three regimens had less favorable safety profiles. Although ipilimumab 0.3 mg/kg was ranked as the best options with the lowest risk of grade >= 3 treatment or immune-related adverse events, less therapeutic benefit was performed. The pembrolizumab 10 mg/kg regimen may be the preferred treatment with relative higher efficiency and safety among the ICIs regi-mens reported, as well as the nivolumab 3 mg/kg regimen. Head-to-head trials showed similar results.Conclusions: This study shown the preferred treatment regimens with relatively higher efficiency and safety among the reported ICI regimens. Our results may complement the current standard of care, while its direct drug comparisons will aid future trials.