The Optimal First‐Line Therapy for Extensive‐Stage Small‐Cell Lung Cancer Based on Liver Metastasis Status: A Network Meta‐Analysis and Systematic Review

Abstract

ABSTRACT Purpose To compare the efficacy of first‐line regimens based on programmed cell death (or ligand) [PD‐(L)1] blockade in extensive‐stage small‐cell lung cancer (ES‐SCLC) patients with or without liver metastases (LM), and to identify optimal treatment strategies. Methods Network meta‐analysis of randomized controlled trials (RCTs) comparing chemo‐immunotherapy (CIT) and chemotherapy (CT) in ES‐SCLC patients stratified by LM. Overall survival (OS) and progression‐free survival (PFS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs). Results Seven RCTs involving 3658 ES‐SCLC patients (1243 with LM, 2415 without LM) were analyzed. For patients with LM, the combination therapies of anti‐PD‐1 + CT (HR, 0.67; 95% CI, 0.54%–0.82%; p < 0.001) and anti‐PD‐L1 + CT + anti‐angiogenesis (HR, 0.84; 95% CI, 0.71%–0.99%; p = 0.042) demonstrated superior efficacy in prolonging OS compared to CT alone. The anti‐PD‐1 + CT regimen had the highest cumulative probability of 91.6% for extending OS in patients with LM. For patients without LM, all CIT regimens resulted in improved OS compared to CT alone, with the regimen of anti‐angiogenesis + anti‐PD‐L1 + CT ranking first and having the highest cumulative probability of 95.5% for prolonging OS. Conclusions CIT is effective for ES‐SCLC patients regardless of LM status. For patients with LM, PD‐1 blockade combined with CT is the best option. For patients without LM, the most beneficial regimen is the combination of anti‐angiogenesis, PD‐L1 blockade, and CT.

Keywords

• immunotherapy
• liver metastases
• meta‐analysis
• small‐cell lung cancer