Survival outcomes of adding stereotactic radiosurgery to dual immune checkpoint blockade in melanoma brain metastases: A systematic review and meta-analysis.

Abstract

9550 Background: Melanoma brain metastases (MBM) carry a poor prognosis and remain understudied in prospective trials. Dual immune checkpoint blockade (ICB) with nivolumab plus ipilimumab (N+I) achieves durable intracranial responses; stereotactic radiosurgery (SRS) is sometimes added but its survival benefit is unclear. Despite the increasing real-world use of SRS in combination with dual ICB, no prior meta-analysis has compared survival outcomes of N+I + SRS versus N+I alone. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.PubMed, Embase, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) and observational/real-world (ORW) studies published from January 2015 to July 1, 2025. Primary outcomes were overall survival (OS) and progression-free survival (PFS).Secondary outcomes included radiologic responses rates assessed by RECIST 1.1 and prognostic biomarkers. Random-effects models were used to pool risk ratios (RRs) and hazard ratios (HRs) with 95%confidence intervals (CIs). Analyses were performed in RevMan and R. Results: From 2,972 records, a total of thirteen studies included (ten ORW studies and three RCTs) met our inclusion criteria, including 2,055 patients. Median age was 57.2 years and 64.28% were male. N+I + SRS significantly improved OS compared with N+I alone (HR = 0.56; 95% CI, 0.44–0.71; p<0.00001). Two-year OS for N+I + SRS (RR = 1.35;95% CI, 1.17-1.55; p<0.0001). Among patients receiving N+I alone, two-year OS was 48% (95% CI, 35–60) and PFS was 52% (95% CI, 45-59). Radiologic response rate with N+I included a complete response rate of 29% (95% CI, 22–37) and a partial response rate of 44% (95% CI,29-59). High lactate dehydrogenase (LDH >2× upper limit of normal) was observed in 37% of patients (95% CI, 20–58) and was associated with inferior survival outcomes. Conclusions: In patients with MBM, the addition of stereotactic radiosurgery with dual immune checkpoint blockade is associated with significant overall survival advantage compared with N+I alone. This first meta-analysis defines the incremental survival benefit of adding SRS to contemporary dual immunotherapy N+I integrating long-term survival outcomes, radiologic response, and prognostic biomarkers. These findings support N+I as the systemic backbone for MBM management and support SRS integration for appropriately selected patients. Prospective trials are warranted to optimize sequencing,timing, and patient selection.