The clinical benefit of adding radiotherapy to ipilimumab in patients with melanoma brain metastasis: a systematic review and meta-analysis.

Combining radiotherapy (RT) with Ipilimumab, a CTLA-4 inhibitor, holds promise in treating metastatic brain melanoma (MBM). Despite promising preclinical evidence, clinical studies evaluating their combined efficacy are limited and varied, necessitating a systematic review and meta-analysis to consolidate evidence and identify predictors of response or resistance in this challenging patient population. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The electronic databases of PubMed, Embase, Scopus, and Web of science were searched on July 9th, 2024, using the relevant key terms without filters. All statistical analysis was performed by STATA v.17. A total of 26 studies with 1059 participants were included. The 1, 2, and 3-year overall survival rates were 0.44 [95% CI: 0.32-0.55], 0.28 [95% CI: 0.17, 0.39], and 0.19 [95% CI: 0.06-0.32], respectively. The pooled 12-month local control and 1-year progression-free survival rate were 0.53 [95% CI: 0.34-0.71] and 0.20 [95%CI: 0.10-0.30]. The pooled overall response rate, partial response rates, and stable disease rate were 0.26 [95% CI: 0.10-0.41], 0.10 [95% CI:0.05-0.15], 0.17 [95%CI:0.10-0.23], and 0.58 [95%CI: 0.45-0.70]. This study demonstrated promising results regarding adding RT to ipilimumab which was associated with significantly higher 1-year OS, 18-month OS, 2-year OS, 3-year OS, overall radiological response rate, and stable disease rate and significantly lower rate of progressive disease rate compared to ipilimumab without RT. However, no significant difference was observed between two groups in 6-month OS, 12-month LC, 1-year PFS, and partial response rate.