The clinical outcomes of combined stereotactic radiosurgery with PD-1/PD-L1 inhibitors in patients with metastatic brain tumors: a systematic review and meta-analysis on the safety and efficacy.

Brain metastases (BM) pose a significant challenge due to limited treatment options and poor prognosis. Combining PD-1/PD-L1 inhibitors with stereotactic radiosurgery (SRS) may enhance tumor control through synergistic effects. This study assessed the efficacy and safety of this combined approach for BM. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Embase, Web of Science, and Scopus up to 27 June 2024. Studies involving PD-1/PD-L1 inhibitors and SRS for BM were included. Outcomes included local control (LC), progression-free survival (PFS), overall survival (OS), radiological response, and adverse events. Data were analyzed using STATA V.17 with a random-effects model. Sixteen studies with 1529 patients were included. Pooled 6- and 12-month LC rates were 85% (95% CI 75-95%) and 84% (95% CI 75-93%), respectively. One- and three-year PFS rates were both 51% (95% CI 39-64% and 41-62%), while one- and two-year OS rates were 67% (95% CI 57-78%) and 30% (95% CI 16-45%). Overall response rate was 61% (95% CI 44-78%), with a complete response rate of 39% (95% CI 25-53%). Adverse radiation effects occurred in 31% (95% CI 3-58%), with radiation necrosis in 12% (95% CI 2-23%). Subgroup analyses showed no significant impact of drug type, primary tumor site, prior treatment, or SRS fractionation on outcomes. Combining PD-1/PD-L1 inhibitors with SRS for BM yields robust local control and improved one-year survival compared to historical data, with manageable toxicities. However, variability in outcomes and lack of comparator groups highlight the need for standardized protocols and prospective trials to optimize treatment strategies and identify predictive biomarkers.