Impact of baseline brain metastases on survival and CNS progression in NSCLC patients treated with immune checkpoint inhibitors in real-world studies: a systematic review and meta-analysis.

Abstract

<h4>Background</h4>Brain metastases (BMs) are common in non-small cell lung cancer (NSCLC) and are associated with poor prognosis. Immune checkpoint inhibitors (ICIs) have improved survival outcomes in NSCLC, but their impact on intracranial progression (IP) and survival, particularly in patients with or without baseline BMs, remains unclear. The objective of this study is to determine whether baseline BM status in patients with NSCLC BMs treated with ICIs impacts IP and survival outcomes.<h4>Methods</h4>A systematic review and meta-analysis were conducted on observational studies published from 2015-2025 across PubMed, Embase, and Cochrane. Studies included NSCLC patients treated with ICIs, stratified by baseline BM status. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for IP, were extracted and pooled using random-effects models. Heterogeneity and risk of bias were assessed.<h4>Results</h4>Of 2,679 screened studies, 12 met the inclusion criteria. Among real-world studies (RWs) (n=12), HRs for OS and PFS were extracted from 10 studies. Pooled analysis showed a modest but significant increase in the hazard of death and PFS for BM+ <i>vs.</i> BM- patients [OS: HR =1.15, 95% confidence interval (CI): 1.04-1.28; PFS: HR =1.19, 95% CI: 1.07-1.32]. Additionally, 11/12 studies found no significant survival differences, and 11/12 reported comparable efficacy of ICIs across groups. In 6 studies reporting raw data, BM- patients had lower odds of IP compared to patients with baseline BMs (pooled OR =0.10, 95% CI: 0.05-0.20).<h4>Conclusions</h4>ICIs appear effective regardless of BM status; however, pooled RWs suggest modestly better survival outcomes in patients without baseline BMs. Additionally, these patients may be at a lower risk for IP. Prospective studies are needed to validate these findings and guide future BM prevention strategies.