Liu Bin, Chen Jie, Luo Mingqi
Department of Pharmacy, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
School of Biological Engineering, Wuhan Polytechnic, Wuhan, China.
Front Oncol. 2025 Apr 16;15:1513774. doi: 10.3389/fonc.2025.1513774. eCollection 2025.
Previous studies have demonstrated that immune checkpoint inhibitors (ICIs) significantly improve prognosis in lung cancer patients with brain metastases (BMs). This systematic review and network meta-analysis aims to evaluate the efficacy and safety of 10 ICIs recommended by the 2024 Chinese Society of Clinical Oncology guidelines for treating non-small cell lung cancer (NSCLC) without driver genes, focusing on NSCLC patients presenting with BMs.
A comprehensive literature search of PubMed, Embase, and the Cochrane Library was conducted through June 2024 to identify eligible controlled trials and head-to-head randomized controlled trials investigating 10 ICIs in NSCLC patients with BMs. Pairwise and network meta-analyses were performed using hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs). Treatment efficacy was ranked hierarchically through the surface under the cumulative ranking curve (SUCRA).
Sixteen trials from 11 studies, encompassing 1,274 NSCLC patients with BMs, were included. The meta-analysis demonstrated that ICIs significantly improved overall survival (OS: HR, 0.66; 95% CI, 0.52-0.85; = 0.001) and progression-free survival (PFS: HR, 0.67; 95% CI, 0.54-0.84; < 0.001). SUCRA ranking identified pembrolizumab as the most effective agent for OS improvement (SUCRA 71%), while camrelizumab showed superior PFS benefits (SUCRA 92%). ICIs were associated with increased objective response rates (RR: 1.52; 95% CI, 1.13-2.06; = 0.006), but elevated risks of immune-mediated adverse events (RR: 2.50; 95% CI, 1.46-4.30; = 0.001) and grade 3-5 immune-mediated adverse events and infusion reaction (RR: 6.39; 95% CI, 1.53-26.69; = 0.011).
ICIs demonstrate superior survival benefits compared to chemotherapy in NSCLC patients with BMs, with pembrolizumab and camrelizumab emerging as optimal choices for OS and PFS improvement, respectively. However, vigilant monitoring of immune-mediated adverse events and infusion reactions remains critical in clinical practice.
既往研究表明，免疫检查点抑制剂（ICIs）可显著改善脑转移（BMs）肺癌患者的预后。本系统评价和网状Meta分析旨在评估2024年中国临床肿瘤学会指南推荐的10种ICIs治疗无驱动基因的非小细胞肺癌（NSCLC）的疗效和安全性，重点关注合并BMs的NSCLC患者。
通过检索PubMed、Embase和Cochrane图书馆，全面检索截至2024年6月的文献，以确定研究10种ICIs用于合并BMs的NSCLC患者的合格对照试验和头对头随机对照试验。采用风险比（HRs）和相对风险（RRs）及95%置信区间（CIs）进行成对和网状Meta分析。通过累积排序曲线下面积（SUCRA）对治疗疗效进行分层排序。
纳入了来自11项研究的16项试验，共1274例合并BMs的NSCLC患者。Meta分析表明，ICIs显著改善了总生存期（OS：HR，0.66；95%CI，0.52 - 0.85；P = 0.001）和无进展生存期（PFS：HR，0.67；95%CI，0.54 - 0.84；P < 0.001）。SUCRA排序确定帕博利珠单抗是改善OS最有效的药物（SUCRA 71%），而卡瑞利珠单抗在PFS方面显示出更好的获益（SUCRA 92%）。ICIs与客观缓解率增加相关（RR：1.52；95%CI，1.13 - 2.06；P = 0.006），但免疫介导不良事件风险升高（RR：2.50；95%CI，1.46 - 4.30；P = 0.001）以及3 - 5级免疫介导不良事件和输液反应风险升高（RR：6.39；95%CI，1.53 - 26.69；P = 0.011）。
与化疗相比，ICIs在合并BMs的NSCLC患者中显示出更好的生存获益，帕博利珠单抗和卡瑞利珠单抗分别成为改善OS和PFS的最佳选择。然而，在临床实践中，密切监测免疫介导不良事件和输液反应仍然至关重要。
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