Efficacy of PD-1 or PD-L1 Inhibitors and Central Nervous System Metastases in Advanced Cancer: A Meta-Analysis

Background: Little is known about the efficacy of programmed cell death protein-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) inhibitors in patients with central nervous system (CNS) metastases. Objective: This study aimed to assess the difference in efficacy of PD-1 or PD-L1 inhibitors in patients with and without CNS metastases. Methods: From inception to March 2020, PubMed and Embase were searched for randomized controlled trials (RCTs) about PD-1 or PD-L1 inhibitors. Only trails with available hazard ratios (HRs) for overall survival (OS) of patients with and without CNS metastases simultaneously would be included. Overall survival hazard ratios and their 95% confidence interval (CI) were calculated, and the efficacy difference between these two groups was assessed in the meantime. Results: A total of 4988 patients (559 patients with CNS metastases and 4429 patients without CNS metastases) from 8 RCTs were included. In patients with CNS metastases, the pooled HR was 0.76 (95%CI, 0.62 to 0.93), while in patients without CNS metastases, the pooled HR was 0.74 (95%CI, 0.68 to 0.79). There was no significant difference in efficacy between these two groups (χ²=0.06 P=0.80). Conclusion: With no significant heterogeneity observed between patients with or without CNS metastases, patients with CNS metastases should not be excluded in the PD-1 or PD-L1 blockade therapy. Future research should permit more patients with CNS metastases to engage in PD-1 or PDL1 blockade therapy and explore the safety of PD-1 or PD-L1 inhibitors in patients with CNS metastases.