Zhang Zhenlong, Lin Yuchen, Chen Shuchen
Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fujian Medical University, Fujian, China.
Department of Thoracic Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, China.
Front Immunol. 2025 May 20;16:1569864. doi: 10.3389/fimmu.2025.1569864. eCollection 2025.
Immune checkpoint inhibitors, particularly anti-PD-1/PD-L1 monoclonal antibodies, have transformed non-small cell lung cancer (NSCLC) treatment. This meta-analysis evaluates the efficacy of neoadjuvant, adjuvant, and perioperative immunotherapy in resectable NSCLC, stratified by PD-L1 expression levels.
We conducted a meta-analysis of 10 randomized controlled trials (RCTs) involving 11 articles, focusing on pathological complete response (pCR), major pathological response (MPR), event-free survival (EFS), and overall survival (OS). These outcomes were stratified by PD-L1 expression levels (<1%, ≥1%, 1-49%, ≥50%).
Immunotherapy significantly improved pCR (OR=4.96, 95% CI=2.88-8.57 for PD-L1<1%; OR=9.58, 95% CI=6.32-14.53 for PD-L1≥1%), MPR (OR=2.86, 95% CI=1.97-4.16 for PD-L1<1%; OR=7.39, 95% CI=4.59-11.88 for PD-L1≥1%), and EFS (HR=0.80, 95% CI=0.70-0.92 for PD-L1<1%; HR=0.53, 95% CI=0.45-0.62 for PD-L1≥1%) across all PD-L1 subgroups. Greatest benefits were observed in PD-L1≥50% subgroup, with ORs for pCR and MPR, and HRs for EFS, showing consistent improvements. OS benefits were significant in PD-L1≥1% patients (HR=0.62, 95% CI=0.49-0.79 for PD-L1≥1%) but uncertain in PD-L1<1% cohorts (HR=1.11, 95% CI=0.86-1.44 for PD-L1<1%). Immunotherapy in perioperative setting demonstrated robust efficacy, with significant pathological response and EFS benefits across all PD-L1 subgroups.
This meta-analysis supports immunotherapy within perioperative care for resectable NSCLC, emphasizing PD-L1 expression as a predictive biomarker. Future studies should optimize patient selection and clarify immunotherapy's role in different treatment settings.
https://www.crd.york.ac.uk/PROSPERO/view/CRD42025644497, identifier CRD42025644497.
免疫检查点抑制剂，尤其是抗程序性死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）单克隆抗体，已经改变了非小细胞肺癌（NSCLC）的治疗方式。本荟萃分析评估了新辅助、辅助和围手术期免疫疗法在可切除NSCLC中的疗效，并根据PD-L1表达水平进行分层。
我们对10项随机对照试验（RCT）进行了荟萃分析，涉及11篇文章，重点关注病理完全缓解（pCR）、主要病理缓解（MPR）、无事件生存期（EFS）和总生存期（OS）。这些结果根据PD-L1表达水平（<1%、≥1%、1%-49%、≥50%）进行分层。
免疫疗法显著改善了所有PD-L1亚组的pCR（PD-L1<1%时，OR=4.96，95%CI=2.88-8.57；PD-L1≥1%时，OR=9.58，95%CI=6.32-14.53）、MPR（PD-L1<1%时，OR=2.86，95%CI=1.97-4.16；PD-L1≥1%时，OR=7.39，95%CI=4.59-11.88）和EFS（PD-L1<1%时，HR=0.80，95%CI=0.70-0.92；PD-L1≥1%时，HR=0.53，95%CI=0.45-0.62）。在PD-L1≥50%亚组中观察到最大益处，pCR和MPR的OR值以及EFS的HR值均显示出持续改善。OS益处在PD-L1≥1%的患者中显著（PD-L1≥1%时，HR=0.62，95%CI=0.49-0.79），但在PD-L1<1%的队列中不确定（PD-L1<1%时，HR=1.11，95%CI=0.86-1.44）。围手术期免疫疗法显示出强大的疗效，在所有PD-L1亚组中均有显著的病理缓解和EFS益处。
本荟萃分析支持在可切除NSCLC的围手术期护理中采用免疫疗法，强调PD-L1表达作为预测生物标志物。未来的研究应优化患者选择，并阐明免疫疗法在不同治疗环境中的作用。
https://www.crd.york.ac.uk/PROSPERO/view/CRD42025644497，标识符CRD42025644497。
