Subgroup analysis of event-free survival.

Background PD-1/PD-L1 inhibitors (PI) have shown promising results in both neoadjuvant and adjuvant therapies for resectable non-small cell lung cancer (NSCLC). However, substantial evidence from large-scale studies is still lacking for their use in the perioperative setting (neoadjuvant plus adjuvant). This meta-analysis aims to evaluate the integration of perioperative PI (PPI) with neoadjuvant chemotherapy for resectable NSCLC. Methods To identify appropriate randomized controlled trials (RCTs), we thoroughly explored six different databases. The primary endpoint was survival, while the secondary measures included pathological responses and adverse events (AEs). Results Six RCTs involving 2941 patients were included. The PPI group significantly improved overall survival (OS) (hazard ratio [HR]: 0.62 [0.51, 0.77]), event-free survival (EFS) (HR: 0.57 [0.51, 0.64]), pathological complete response (risk ratio [RR]: 5.81 [4.47, 7.57]), and major pathological response (RR: 2.60 [1.77, 3.82]). Benefits in EFS were seen across all subgroups. OS rates at 12–48 months and EFS rates at 6–48 months were higher in the PPI cohort. Furthermore, the advantages in OS and EFS increased with prolonged survival times. The PPI group also exhibited higher rates of surgery and R0 resections. However, the PPI group experienced more grade 3–5 AEs, serious AEs, and treatment discontinuations due to AEs. Conclusions The integration of perioperative PI with neoadjuvant chemotherapy can significantly improve survival and pathological responses for resectable NSCLC. However, the increased incidence of grade 3–5 AEs must be carefully evaluated.背景 PD-1/PD-L1抑制剂（PD-1/PD-L1 inhibitors）在可切除非小细胞肺癌（non-small cell lung cancer, NSCLC）的新辅助与辅助治疗中均展现出可观的临床获益。然而，针对围手术期（新辅助联合辅助治疗）应用此类药物的大规模研究证据仍较为匮乏。本项荟萃分析旨在评估围手术期PD-1/PD-L1抑制剂（perioperative PI, PPI）联合新辅助化疗用于可切除NSCLC的治疗价值。 方法 为筛选符合要求的随机对照试验（randomized controlled trials, RCTs），研究团队系统检索了6个独立数据库。本研究的主要终点为生存结局，次要评价指标包括病理应答情况与不良事件（adverse events, AEs）。 结果 最终纳入6项随机对照试验，共计2941例受试者。围手术期PD-1/PD-L1抑制剂组的总生存期（overall survival, OS）显著改善（风险比[HR]：0.62 [95%置信区间：0.51, 0.77]），无事件生存期（event-free survival, EFS）（HR：0.57 [0.51, 0.64]）、病理完全缓解（pathological complete response, pCR）（相对危险度[RR]：5.81 [4.47, 7.57]）以及主要病理应答（major pathological response, MPR）（RR：2.60 [1.77, 3.82]）均得到显著提升。所有亚组均观察到无事件生存期的临床获益。围手术期PD-1/PD-L1抑制剂组患者的12~48个月总生存期率与6~48个月无事件生存期率均更高。此外，总生存期与无事件生存期的获益随随访时长延长而愈发显著。该组患者的手术完成率与R0切除率亦显著升高。但围手术期PD-1/PD-L1抑制剂组出现更多3~5级不良事件、严重不良事件以及因不良事件导致的治疗中断情况。 结论 围手术期PD-1/PD-L1抑制剂联合新辅助化疗可显著改善可切除非小细胞肺癌患者的生存结局与病理应答水平，但需审慎评估其3~5级不良事件发生率升高的潜在风险。