Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

扫码查看

原文链接

NETL
NSTL
万方数据

外文摘要：Objective:Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive)gastric cancer(GC)vary in different clinical studies,making it difficult to optimize anti-CLDN18.2 therapy.We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.Methods:A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01 clinical trials were included in the analysis.CLDN18.2 expression on ≥40％of tumor cells(2+,40％)and CLDN18.2 expression on ≥70％of tumor cells(2+,70％)were considered the two levels of positively expressed GC.The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.Results:CLDN18.2 was expressed in 57.6％(cut-off:2+,40％)and 48.9％(cut-off:2+,70％)of patients.Programmed death-ligand 1(PD-L1)and CLDN18.2 were co-expressed in 19.8％[combined positive score(CPS)≥1,CLDN18.2(cut-off:2+,40％)]and 17.2％[CPS≥5,CLDN18.2(cut-off:2+,70％)]of patients.CLDN18.2 expression positively correlated with younger age,female sex,non-gastroesophageal junction(non-GEJ),and diffuse phenotype(P＜0.001).HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P＜0.05).Uterine adnexa metastasis(P＜0.001)was more frequent and liver metastasis(P＜0.001)was less common in CLDN18.2-positive GC.Overall survival and immunotherapy-related progression-free survival(irPFS)were inferior in the CLDN18.2-positive group.Conclusions:CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes.The combination of anti-CLDN18.2 therapy,anti-PD-L1/PD-1 therapy,and chemotherapy for GC requires further investigation.

外文关键词：

Gastric cancerclaudin18.2CT041PD-L1immunotherapy

作者：

Changsong Qi、Xiaoyi Chong、Ting Zhou、Mingyang Ma、Jifang Gong、Miao Zhang、Jian Li、Jun Xiao、Xiaohui Peng、Zhen Liu、Zonghai Li、Lin Shen、Xiaotian Zhang

展开 >

作者单位：

State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers,Beijing Key Laboratory of Carcinogenesis and Translational Research,Department of Gastrointestinal Oncology,Peking University Cancer Hospital & Institute,Beijing 100142,China

Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing),Department of Gastrointestinal Oncology,Peking University Cancer Hospital & Institute,Beijing 100142,China

CARsgen Therapeutics Co.,Ltd,Shanghai 200231,China

CARsgen Life Sciences Co.,Ltd,Shanghai 200131,China

展开 >

基金：

Beijing Natural Science FoundationNational Natural Science Foundation of China

项目编号：

Z20J0010582272627

出版年：

2024

DOI：

10.21147/j.issn.1000-9604.2024.01.08

中国癌症研究(英文版)