Yuan Zhen, Cui Hao, Wang Shuyuan, Liang Wenquan, Cao Bo, Song Liqiang, Liu Guibin, Huang Jun, Chen Lin, Wei Bo
School of Medicine, Nankai University, Tianjin, China.
Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
Front Oncol. 2023 Jan 26;13:1103320. doi: 10.3389/fonc.2023.1103320. eCollection 2023.
Immune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment.
PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs).
A total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%-25.5%] and 44.0% (95% CI, 34.1%-53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%-94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%-66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%-99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)].
This systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population.
免疫检查点抑制剂（ICIs）在局部晚期、可切除的胃或胃食管交界腺癌（GC/GEJC）免疫治疗中显示出了良好的前景，但其在新辅助治疗中的疗效仍不明确。本研究旨在评估将程序性细胞死亡蛋白1（PD-1）/程序性细胞死亡配体1（PD-L1）抑制剂纳入GC/GEJC新辅助化疗（NACT）的疗效和安全性。
截至2022年11月19日，系统检索了PubMed、Cochrane图书馆、Embase、ClinicalTrials.gov和主要肿瘤学会议数据库，纳入评估PD-1/PD-L1抑制剂联合NACT疗效和安全性的随机对照试验（RCT）和队列研究。主要结局指标为病理完全缓解（pCR）、主要病理缓解（MPR）、R0切除率和治疗相关不良事件（TRAEs）。
本荟萃分析共纳入了来自20项前瞻性研究的753例患者。报告研究的汇总pCR率和MPR率分别为21.7%[95%置信区间（CI），18.1%-25.5%]和44.0%（95%CI，34.1%-53.8%）。总TRAEs的汇总发生率为89.1%（95%CI，82.7%-94.3%），3-4级TRAEs的发生率为34.4%（95%CI，17.8%-66.5%）。报告的汇总R0切除率为98.9%（95%CI，97.0%-99.9%）。亚组分析未发现不同PD-1/PD-L1抑制剂在疗效和安全性上存在显著差异。此外，PD-L1表达阳性（联合阳性评分≥1）患者的疗效与整个研究人群相当[pCR，22.5%对21.2%（p>0.05）；MPR，48.6%对43.7%（p>0.05）]。
本系统评价和荟萃分析发现，PD-1/PD-L1抑制剂联合NACT治疗局部晚期GC/GEJC耐受性良好，可能具有治疗优势。将ICIs纳入NACT已显示出在任何PD-L1表达人群中应用的潜力。
