Efficacy of Immune Checkpoint Inhibitors in Non-small-cell Lung Cancer Patients With Different Metastatic Sites: A Systematic Review and Meta-Analysis

Background: Organ-specific response patterns reported in previous studies indicate different response toward immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) patients with different metastatic sites. This study aims to compare the efficacy of ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. Materials and Methods: MEDLINE, Embase, and CENTRAL were searched for studies comparing ICIs with conventional therapy in NSCLC patients with bone, brain or liver metastases. The pooled hazard ratio (HR) of overall survival (OS) and progression-free survival (PFS) among included studies was analyzed using the random effects model. Results: Eight studies consisting of 988 NSCLC patients were included, 259 with brain metastases and 729 with liver metastases. No available study with bone metastases information was identified. For patients with brain metastases, ICIs significantly improved their OS (HR, 0.57; P = 0.007). For patients with liver metastases, both OS (HR, 0.72; P = 0.006), and PFS (HR, 0.72; P = 0.004) improvements were observed in the ICI treatment arm. Subgroup analysis was conducted based on target of ICIs and treatment regimen. PD-1 inhibitors could benefit patients with liver or brain metastases on OS and PFS (brain metastases: OS, HR, 0.43; P < 0.001; liver metastases: PFS, HR, 0.52; P = 0.003; OS, HR, 0.66; P = 0.001), while PD-L1 inhibitors could not. Patients with brain metastases could only gain OS improvement from ICIs combined with chemotherapy (HR, 0.41; P = 0.001), but for patients with liver metastases, the benefit was detected using ICIs single agent (HR, 0.68; P = 0.012) or ICIs combined with chemotherapy plus anti-VEGF therapy (HR, 0.52; P = 0.005). Conclusion: ICIs could significantly improve OS in NSCLC patients with brain or liver metastases compared with conventional therapy. Patients with brain metastases could only gain OS benefit from ICIs combined with chemotherapy, while those with liver metastases obtained superior OS from ICIs single agent or ICIs combined with chemotherapy plus anti-VEGF therapy.