Radiotherapy and Immunotherapy in Melanoma Brain Metastases

Melanoma brain metastasis (MBM) generally portends a dismal prognosis. Simultaneous use of radiotherapy (RT) and immune checkpoint inhibitor (ICI) therapy demonstrated tremendous promise and emerged as the new standard. This meta-analysis was conducted to evaluate survival outcomes and toxicities of this combination in patients with MBM. Data analyses were performed using Comprehensive Meta-Analysis software (version 2) and IBM SPSS software (version 27).

A systematic literature search of PubMed, EMBASE, and the Cochrane Library (via Wiley) was conducted using PICOS/PRISMA selection protocol and included studies to evaluate survival and safety-associated outcomes of ICI + RT for the treatment of MBM.

A total 44 studies involving 2498 patients were reviewed. The pooled effect size (ES) for overall survival (OS) to compare the ICI + RT arm and ICI alone arm (HR: 0.693 [0.526-0.913, p = .001]), and compare the ICI + RT arm and brain RT alone (HR: 0.595 [0.489-0.723, p < .001)] indicated better survival outcomes in ICI + RT versus RT alone and ICI alone arms. Comparing central nervous system toxicity in the ICI + RT arm and RT alone arm, the pooled ES Grade ≥ 3 neurologic adverse events (NAEs) risk ratio ([RR] = 1.425; 95% confidence interval [CI]: 0.485-4.183; p = .519) indicated that ICI + RT nonsignificantly increased Grade 3-4 NAEs. Comparing Grade ≥ 3 radiation necrosis in the ICI + RT arm and RT alone arm, the pooled ES RR (RR = 2.73; 95% CI: 0.59-12.59; p = .199) indicated that ICI + RT nonsignificantly increased Grade ≥ 3 radiation necrosis.

Concurrent administration of RT and ICI evinced favorable OS outcomes and acceptable safety profile in MBM patients. Planned prospective trials are required to demonstrate the issue.