文章：

针对表达Claudin 18.2与PD-L1的HER2阴性转移性胃癌患者的治疗选择

Treatment Selection for Patients with HER2-Negative Metastatic Gastric Cancer Expressing Claudin 18.2 and PD-L1

原文发布日期：27 March 2025

DOI: 10.3390/cancers17071120

类型: Article

开放获取: 是

英文摘要：

Combination therapy of chemotherapy and zolbetuximab demonstrated a significant survival benefit compared to chemotherapy alone in patients with human epidermal growth factor receptor 2 (HER2)-negative, claudin (CLDN) 18.2–positive metastatic gastric cancer (mGC). Consequently, it has been approved as a standard first-line therapy for these patients. Combination therapy of chemotherapy and immune checkpoint inhibitors (ICIs)—either nivolumab or pembrolizumab—is a standard first-line therapy for patients with HER2-negative mGCs that are positive for programmed death-ligand 1 (PD-L1) expression, as defined by a combined positive score (CPS). Although approximately 13–22% of CLDN-positive mGCs are also CPS-positive, optimal treatment for mGC patients expressing both CLDN and PD-L1 remains undetermined due to the absence of direct comparative studies between zolbetuximab and ICIs. Treatment selection under this condition has become a critical issue. In this review, we discuss the appropriate treatment selection for HER2-negative mGC patients who are double-positive for CLDN 18.2 and PD-L1 based on clinical data and differences in the mechanism of action and safety profile between zolbetuximab and ICI.

摘要翻译： 

与单纯化疗相比，化疗联合佐贝妥昔单抗治疗人表皮生长因子受体2（HER2）阴性、紧密连接蛋白（CLDN）18.2阳性的转移性胃癌（mGC）患者显示出显著的生存获益，因此已被批准作为此类患者的标准一线治疗方案。化疗联合免疫检查点抑制剂（ICIs）——纳武利尤单抗或帕博利珠单抗——是程序性死亡配体1（PD-L1）表达阳性（以联合阳性评分[CPS]定义）的HER2阴性mGC患者的标准一线治疗。尽管约13-22%的CLDN阳性mGC患者同时为CPS阳性，但由于缺乏佐贝妥昔单抗与ICIs之间的直接比较研究，同时表达CLDN和PD-L1的mGC患者的最佳治疗方案尚未确定。在此情况下如何选择治疗方案已成为一个关键问题。本文基于临床数据，并结合佐贝妥昔单抗与ICI在作用机制和安全性方面的差异，探讨了CLDN 18.2与PD-L1双阳性的HER2阴性mGC患者的适宜治疗选择。

原文链接：

Treatment Selection for Patients with HER2-Negative Metastatic Gastric Cancer Expressing Claudin 18.2 and PD-L1