Petrelli Fausto, Dottorini Lorenzo, Rossitto Mauro, Meriggi Fausto, Cherri Sara, Zaniboni Alberto, Ghidini Antonio
Oncology Unit, ASST Bergamo Ovest, Treviglio (BG), Italy.
Oncology Unit, Fondazione Poliambulanza, Brescia, Italy.
Transl Lung Cancer Res. 2025 Aug 31;14(8):3067-3075. doi: 10.21037/tlcr-2025-185. Epub 2025 Aug 26.
The optimal timing for immune checkpoint inhibitor (ICI) therapy in patients with operable non-small cell lung cancer (NSCLC) remains a subject of clinical uncertainty. This Bayesian network meta-analysis (NMA) aimed to compare the efficacy of ICIs administered in neoadjuvant, adjuvant, and perioperative settings.
A systematic review of randomized controlled trials (RCTs) published up to September 1, 2024, identified eight eligible studies comprising a total of 3,659 patients. Primary outcomes included disease-free survival (DFS) and event-free survival (EFS). A Bayesian framework was used to estimate hazard ratios (HRs) and 95% credible intervals (CrIs), with treatment efficacy ranked using the surface under the cumulative ranking curve (SUCRA). Risk of bias was assessed using the Cochrane Risk of Bias tool, and sensitivity analyses confirmed the robustness of the findings after exclusion of studies at higher risk.
Perioperative ICIs demonstrated superior efficacy compared with neoadjuvant or adjuvant strategies. Specifically, perioperative toripalimab plus chemotherapy ranked first (SUCRA =0.99; rank 1 probability =87%), followed by perioperative nivolumab (SUCRA =0.94). Both regimens significantly reduced the risk of disease recurrence or progression compared to surgery alone or standard chemotherapy. While neoadjuvant and adjuvant ICIs provided moderate benefit, they ranked lower in overall efficacy. Sensitivity analyses excluding higher-risk studies did not substantially alter the results, confirming their robustness. No direct comparisons were available between all strategies, and heterogeneity in control arms, ICI agents, programmed death ligand-1 (PD-L1) inclusion thresholds, and follow-up duration limit cross-trial comparability. Additionally, long-term overall survival data were largely immature across studies.
These findings suggest that perioperative administration of ICIs, particularly toripalimab and nivolumab in combination with chemotherapy, may offer the most effective approach to improving DFS/EFS in resectable NSCLC. However, further head-to-head trials, longer follow-up, and biomarker-stratified analyses are needed to confirm these results and guide personalized treatment decisions.
可手术切除的非小细胞肺癌（NSCLC）患者免疫检查点抑制剂（ICI）治疗的最佳时机仍是临床存在不确定性的一个问题。这项贝叶斯网络荟萃分析（NMA）旨在比较新辅助、辅助和围手术期应用ICI的疗效。
对截至2024年9月1日发表的随机对照试验（RCT）进行系统评价，确定了8项符合条件的研究，共纳入3659例患者。主要结局包括无病生存期（DFS）和无事件生存期（EFS）。采用贝叶斯框架估计风险比（HRs）和95%可信区间（CrIs），使用累积排名曲线下面积（SUCRA）对治疗效果进行排名。使用Cochrane偏倚风险工具评估偏倚风险，敏感性分析在排除高风险研究后证实了研究结果的稳健性。
围手术期应用ICI与新辅助或辅助策略相比显示出更好的疗效。具体而言，围手术期应用托瑞帕利单抗联合化疗排名第一（SUCRA =0.99；排名第一的概率 =87%），其次是围手术期应用纳武利尤单抗（SUCRA =0.94）。与单纯手术或标准化疗相比，这两种方案均显著降低了疾病复发或进展的风险。虽然新辅助和辅助ICI有一定益处，但在总体疗效方面排名较低。排除高风险研究的敏感性分析并未实质性改变结果，证实了其稳健性。所有策略之间没有直接比较，对照臂、ICI药物、程序性死亡配体-1（PD-L1）纳入阈值以及随访持续时间的异质性限制了跨试验的可比性。此外，各研究中的长期总生存数据大多不成熟。
这些发现表明，围手术期应用ICI，特别是托瑞帕利单抗和纳武利尤单抗联合化疗，可能是改善可切除NSCLC患者DFS/EFS的最有效方法。然而，需要进一步的头对头试验、更长时间的随访以及生物标志物分层分析来证实这些结果并指导个性化治疗决策。
