Zhao Weixing, Li Bo, Gu Yujia, Jin Xiaoni, Li Zirui, Guo Wanjing, Lu Xinxin, Jiang Jun
Affiliated Hospital of Qinghai University, Qinghai, China.
BMC Cancer. 2025 Aug 18;25(1):1332. doi: 10.1186/s12885-025-14712-w.
OBJECTIVE: This study aimed to systematically evaluate the efficacy and safety of combination therapies with immune checkpoint inhibitors (ICIs) in patients with driver gene-negative non-small cell lung cancer (NSCLC) and liver metastases. These patients typically have poor prognosis and limited responses to immunotherapy. This study synthesized existing literature by conducting a network meta-analysis to determine the most effective first-line ICI combination regimen to guide clinical treatment decisions. METHODS: We systematically searched the PubMed, Embase, Web of Science, and Cochrane Library databases for Phase III randomised controlled trials published up to 1 August 2024. Eligible studies underscored on patients with driver gene-negative NSCLC with liver metastases and reported progression-free survival (PFS), overall survival (OS), and treatment-related adverse events. Bayesian network meta-analysis was conducted using R (version 4.4.1) and STATA (version 17), with the results reported as hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Fourteen studies including 1,291 patients and 11 ICIs combination regimens were included. Pembrolizumab plus chemotherapy remarkably improved OS (HR, 0.64; 95% CI, 0.41-0.98). For PFS, tislelizumab plus chemotherapy (HR, 0.44; 95% CI, 0.26-0.74) and pembrolizumab plus chemotherapy (HR, 0.59; 95% CI, 0.39-0.90) were superior to other treatments. PD-1 inhibitors, such as pembrolizumab, combined with chemotherapy have shown greater efficacy than PD-L1 inhibitors, particularly for non-squamous cell carcinoma. High-grade adverse events, including hepatotoxicity, were more frequent in patients with liver metastases. CONCLUSION: ICI-chemotherapy combinations offer a promising first-line treatment for driver gene-negative NSCLC with liver metastases. The pembrolizumab and tislelizumab combination demonstrated improved OS and PFS with distinct efficacy and safety profiles. Enhanced monitoring of liver function is recommended because of the risk of hepatotoxicity. Further studies are needed to confirm these findings and optimise individualised treatment strategies.
目的：本研究旨在系统评价免疫检查点抑制剂（ICI）联合疗法对驱动基因阴性的非小细胞肺癌（NSCLC）伴肝转移患者的疗效和安全性。这些患者通常预后较差，对免疫治疗反应有限。本研究通过进行网络荟萃分析来综合现有文献，以确定最有效的一线ICI联合治疗方案，从而指导临床治疗决策。 方法：我们系统检索了截至2024年8月1日发表的PubMed、Embase、Web of Science和Cochrane图书馆数据库中的III期随机对照试验。符合条件的研究重点关注驱动基因阴性的NSCLC伴肝转移患者，并报告无进展生存期（PFS）、总生存期（OS）和治疗相关不良事件。使用R（版本4.4.1）和STATA（版本17）进行贝叶斯网络荟萃分析，结果以风险比（HR）和95%置信区间（CI）表示。 结果：纳入了14项研究，共1291例患者以及11种ICI联合治疗方案。帕博利珠单抗联合化疗显著改善了总生存期（HR，0.64；95%CI，0.41 - 0.98）。对于无进展生存期，替雷利珠单抗联合化疗（HR，0.44；95%CI，0.26 - 0.74）和帕博利珠单抗联合化疗（HR，0.59；95%CI，0.39 - 0.90）优于其他治疗。PD - 1抑制剂，如帕博利珠单抗，联合化疗显示出比PD - L1抑制剂更高的疗效，尤其是对于非鳞状细胞癌。包括肝毒性在内的高级别不良事件在肝转移患者中更为常见。 结论：ICI - 化疗联合方案为驱动基因阴性的NSCLC伴肝转移提供了一种有前景的一线治疗方法。帕博利珠单抗和替雷利珠单抗联合方案显示出改善的总生存期和无进展生存期，具有不同的疗效和安全性特征。由于存在肝毒性风险，建议加强肝功能监测。需要进一步研究来证实这些发现并优化个体化治疗策略。
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