Efficacy of different therapies for brain metastases of non-small cell lung cancer: a systematic review and meta-analysis.

Background: As one of the most common causes of death in advanced non-small cell lung cancer (NSCLC), brain metastases (BM) have attracted attention and debate about treatment options, especially for patients with negative driver genes or resistance to targeted agents. Therefore, we conducted a meta-analysis to investigate the potential benefit of different therapeutic regimens for intracranial lesions in non-targeted therapy NSCLC patients. Methods: A comprehensive search was conducted in databases including PubMed, Embase, and the Cochrane Library. The primary endpoints included the intracerebral objective response rate (icORR) and intracerebral progression-free survival (iPFS) in patients with BM. Results: Thirty-six studies involving 1,774 NSCLC patients with baseline BM were included in this meta-analysis. Antitumor agents plus radiotherapy (RT) showed the most significant synergistic effects; the highest pooled icORR that appeared in the combination of immune checkpoint inhibitor (ICI) and RT was 81% [95% confidence interval (CI): 16-100%], and the median iPFS was 7.04 months (95% CI: 2.54-11.55 months). The pooled icORR and median iPFS of RT plus chemotherapy were 46% (95% CI: 34-57%) and 5.7 months (95% CI: 3.90-7.50 months), respectively. The highest median iPFS in nivolumab plus ipilimumab plus chemotherapy was 13.5 months (95% CI: 8.35-18.65 months). ICI plus chemotherapy also showed potent antitumor activity in BM, with a pooled icORR of 56% (95% CI: 29-82%) and a median iPFS of 6.9 months (95% CI: 3.20-10.60 months). Notably, the subgroup analysis indicated that the pooled icORR of patients in programmed cell death-ligand 1 (PD-L1) (≥50%) who received ICI was 54% (95% CI: 30-77%), and that of patients who received first-line ICI was 69.0% (95% CI: 51-85%). Conclusions: ICI-based combination treatment provides a long-term survival benefit for non-targeted therapy patients, with the most significant benefits observed in improving icORR and prolonging overall survival (OS) and iPFS. In particular, patients who received first-line treatment or who were PD-L1-positive had a more significant survival benefit from aggressive ICI-based therapies. For patients with a PD-L1-negative status, chemotherapy plus RT led to better clinical outcomes than other treatment regimens. These innovative findings could help clinicians to better select therapeutic strategies for NSCLC patients with BM.