Yu Zhiyuan, Liang Chen, Xu Qixuan, Yuan Zhen, Chen Miao, Li Rui, Zhou Sixin, Li Peiyu, Wei Bo, Zhao Xudong
Medical School of Chinese PLA.
Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing.
Int J Surg. 2025 Jan 1;111(1):1415-1426. doi: 10.1097/JS9.0000000000002056.
The extensive utilization of immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) has achieved significant advancements in the treatment of diverse solid tumors. The present meta-analysis aims to evaluate the safety and efficacy of neoadjuvant chemotherapy (NCT) plus PD-1 inhibitors for patients with locally advanced gastric cancer (LAGC).
An electronic search of PubMed, EmBase, and the Cochrane Library was performed to identify the clinical trials of NCT + PD-1 inhibitor vs. NCT in patients with LAGC. The retrieval period extended from the establishment of the corresponding database until April 2024, and meta-analysis was conducted using Stata (version 15) software. Subsequently, direct comparative analysis was used to compare pooled results of neoadjuvant immunochemotherapy (NICT) with NCT.
After screening, six phase II/III randomized controlled trials (RCTs) and nine retrospective studies with 2953 patients were included. In meta-analysis, the NICT group demonstrated a significantly higher rate of pathological complete response (pCR) ( P <0.001) and R0 resection ( P =0.001), and a lower 2-year recurrence rate ( P =0.001) compared to the NCT group. The NICT group, however, exhibited a higher incidence of severe treatment-related adverse events (TRAEs) ( P =0.044). Additionally, the NICT and NCT groups exhibited no statistical differences in terms of the number of harvested lymph nodes, the occurrence of total TRAEs and postoperative complications, as well as the duration of postoperative hospitalization.
The combination of PD-1 inhibitor + NCT in LAGC patients enhances the likelihood of achieving radical surgery and improves prognosis, albeit to some extent increasing the risk of severe TRAEs. NICT is anticipated to emerge as the preferred neoadjuvant therapy option for patients diagnosed with LAGC.
靶向程序性细胞死亡蛋白1（PD-1）的免疫检查点抑制剂（ICIs）的广泛应用在多种实体瘤的治疗中取得了显著进展。本荟萃分析旨在评估新辅助化疗（NCT）联合PD-1抑制剂治疗局部晚期胃癌（LAGC）患者的安全性和疗效。
对PubMed、EmBase和Cochrane图书馆进行电子检索，以确定LAGC患者中NCT + PD-1抑制剂与NCT的临床试验。检索期从相应数据库建立至2024年4月，并使用Stata（15版）软件进行荟萃分析。随后，采用直接比较分析将新辅助免疫化疗（NICT）与NCT的汇总结果进行比较。
筛选后，纳入了6项II/III期随机对照试验（RCT）和9项回顾性研究，共2953例患者。在荟萃分析中，与NCT组相比，NICT组的病理完全缓解（pCR）率（P <0.001）和R0切除率（P =0.001）显著更高，2年复发率更低（P =0.001）。然而，NICT组严重治疗相关不良事件（TRAEs）的发生率更高（P =0.044）。此外，NICT组和NCT组在收获淋巴结数量、总TRAEs和术后并发症的发生情况以及术后住院时间方面无统计学差异。
PD-1抑制剂联合NCT用于LAGC患者可提高根治性手术的可能性并改善预后，尽管在一定程度上增加了严重TRAEs的风险。NICT有望成为诊断为LAGC患者的首选新辅助治疗方案。
