Nie Run-Cong, Chen Xiao-Jiang, Liang Cheng-Cai, Zhao Bai-Wei, Wang Wei, Zhang Fei-Yang, Cai Mu-Yan, Qiu Hai-Bo, Xue Zhi-Cheng, Chen Guo-Ming, Liu Zhi-Min, Chi Jun, Duan Jin-Ling, Zhang Dong-Sheng, Chen Ying-Bo, Zhou Zhi-Wei, Chen Yong-Ming, Yuan Shu-Qiang, Li Yuan-Fang
Department of Gastric Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, P.R. China.
Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou 510060, P.R. China.
Cell Rep Med. 2025 Jun 17;6(6):102190. doi: 10.1016/j.xcrm.2025.102190.
The use of trastuzumab and programmed death-1 (PD-1) inhibitor is effective in patients with HER2-positive advanced gastric or gastro-esophageal junction cancer; however, their use has not been investigated in patients with localized disease. This phase 2 trial evaluates the safety and efficacy of dual PD-1 (sintilimab) and HER2 blockade with chemotherapy in patients with resectable HER2-positive gastric and gastro-esophageal junction adenocarcinoma. 22 patients are enrolled, and 20 patients undergo surgery. The primary endpoint is achieved; 12 (55%, 95% confidence interval [CI]: 32-76) of 22 patients have a major pathological response, and 11 (50%, 95% CI: 28-72) of 22 patients achieve pathological complete response. The most common grade 3 treatment-related adverse events are neutropenia and thrombocytopenia. No treatment-related deaths occur. Transcriptomic analysis, bioinformatics analysis, and immunofluorescence staining demonstrate that regulatory T cells are associated with possibility of drug resistance. This study was registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2200058732).
曲妥珠单抗和程序性死亡受体1（PD-1）抑制剂对HER2阳性晚期胃癌或胃食管交界癌患者有效；然而，其在局限性疾病患者中的应用尚未得到研究。这项2期试验评估了双重PD-1（信迪利单抗）和HER2阻断联合化疗在可切除的HER2阳性胃和胃食管交界腺癌患者中的安全性和疗效。共纳入22例患者，其中20例接受了手术。达到了主要终点；22例患者中有12例（55%，95%置信区间[CI]：32-76）出现主要病理反应，22例患者中有11例（50%，95%CI：28-72）达到病理完全缓解。最常见的3级治疗相关不良事件是中性粒细胞减少和血小板减少。未发生与治疗相关的死亡。转录组分析、生物信息学分析和免疫荧光染色表明，调节性T细胞与耐药可能性相关。本研究已在中国临床试验注册中心注册（标识符：ChiCTR2200058732）。
