Efficacy and Safety of Combined Brain Radiotherapy and Immunotherapy in Non-Small-Cell Lung Cancer With Brain Metastases: A Systematic Review and Meta-Analysis

Abstract

Background: Immune checkpoint inhibitors (ICIs) are recommended to treat advanced non-small-cell lung cancer (NSCLC), whereas brain radiotherapy (RT) is the mainstream therapy for patients with brain metastases (BMs). This systematic review and meta-analysis investigated whether the combination of brain RT and ICIs would generate a synergistic effect without unacceptable toxicity to treat NSCLC with BMs.

Methods: Literature searching was performed in PubMed, Embase, Web Of Science, and The Cochrane Library up to December 20, 2020. Heterogeneity, sensitivity analysis, forest plots, and publication bias were analyzed using Stata 15.0.

Results: Nineteen studies were included. In the comparison of the brain RT+ICIs arm and brain RT alone arm, the pooled effect size (ES) for overall survival (OS) (hazard ratio [HR] = 0.77; 95% confidence interval [CI] 0.71-0.83; I² = 0; P < .001; n = 4) and grade 3-4 neurological adverse events (AEs) (risk ratio [RR] = 0.91; 95% CI 0.41-2.02; I² = 26.5; P = .809; n = 4) indicated that the brain RT+ICIs model had significantly better systemic efficacy and similar neurological AEs compared with brain RT alone for NSCLC. Concurrent RT+ICIs were identified as the optimal model, which achieved the best efficacy without significantly increased AEs compared with sequential RT+ICIs.

Conclusions: Combined ICIs and brain RT exhibited favorable efficacy and acceptable toxicity for NSCLC patients with BMs, among which, the concurrent model might be the optimal option. Our results could guide the design of future randomized controlled trials and clinical practice.

Keywords: Advanced non-small-cell lung cancer; Brain radiotherapy; Combined therapy; Immune checkpoint inhibitors.