Efficacy of addition immune checkpoint inhibitors to chemotherapy as first-line treatment for small cell lung cancer patients with liver or brain metastases: a systematic review and meta-analysis.

Abstract

Differential organ-specific tumor response to immune checkpoint inhibitors (ICIs) has been reported in multiple solid tumors. We aim at investigating the efficacy differences of ICIs combined with chemotherapy (CT) vs. CT alone as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). We searched PubMed, Embase, Medline, and China National Knowledge Infrastructure databases to identify relevant trials comparing ICIs combined with CT vs. CT alone in ES-SCLC patients with brain or liver metastases. The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS). The pooled hazard ratio (HR) was analyzed using the fixed or random effects model, according to heterogeneity among included trials. We identified 5 randomized controlled trials of 8 studies that involved a total of 1,401 patients, 310 with brain metastases and 1,091 with liver metastases. The quality of included trials was high. The pooled results showed that ICIs combined with CT significantly improved OS of ES-SCLC with liver metastases (HR 0.88, 95%CI: 0.78-1.00, p=0.049), and a tendency to improve PFS (HR 0.86, 95%CI: 0.68-1.07, p=0.17). For patients with brain metastases, no survival benefit could be obtained from combination therapy of ICIs with CT in terms of PFS (HR 0.91, 95%CI: 0.63-1.32, p=0.62) and OS (HR 1.12, 95%CI: 0.88-1.43, p=0.36). No publication bias was detected. The addition of ICIs to CT significantly improves OS in ES-SCLC patients with liver metastases compared with CT alone. No survival benefit could be obtained from ICIs and CT combination therapy for ES-SCLC with brain metastases.