Miyajima Yusuke, Kawakami Takeshi
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan.
Cancers (Basel). 2025 Mar 27;17(7):1120. doi: 10.3390/cancers17071120.
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.
与单纯化疗相比，化疗联合zolbetuximab治疗在人表皮生长因子受体2（HER2）阴性、claudin（CLDN）18.2阳性的转移性胃癌（mGC）患者中显示出显著的生存获益。因此，它已被批准作为这些患者的标准一线治疗方案。化疗联合免疫检查点抑制剂（ICI）——纳武利尤单抗或帕博利珠单抗——是程序性死亡配体1（PD-L1）表达呈阳性（由联合阳性评分（CPS）定义）的HER2阴性mGC患者的标准一线治疗方案。虽然大约13%-22%的CLDN阳性mGC患者也为CPS阳性，但由于zolbetuximab和ICI之间缺乏直接的对比研究，CLDN和PD-L1均表达阳性的mGC患者的最佳治疗方案仍未确定。在这种情况下，治疗选择已成为一个关键问题。在这篇综述中，我们根据临床数据以及zolbetuximab和ICI在作用机制和安全性方面的差异，讨论CLDN 18.2和PD-L1均呈双阳性的HER2阴性mGC患者的合适治疗选择。
