Zhang SH, Li W, Chen XY, Nie LL. Combining immune checkpoint inhibitors with standard treatment regimens in advanced human epidermal growth factor receptor-2 positive gastric cancer patients. World J Gastrointest Oncol 2025; 17(4): 103855 [DOI: 10.4251/wjgo.v17.i4.103855]
Corresponding Author of This Article
Le-Le Nie, Chief Physician, Department of General Surgery, The First People’s Hospital of Fuzhou City, No. 1099 Yingbin Avenue, Fuzhou 344000, Jiangxi Province, China. nielele520@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical Trials Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Apr 15, 2025; 17(4): 103855 Published online Apr 15, 2025. doi: 10.4251/wjgo.v17.i4.103855
Combining immune checkpoint inhibitors with standard treatment regimens in advanced human epidermal growth factor receptor-2 positive gastric cancer patients
Sheng-Hu Zhang, Wan Li, Xi-Yan Chen, Le-Le Nie
Sheng-Hu Zhang, Department of Oncology, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze university, Jingzhou 434020, Hubei Province, China
Wan Li, Department of Ultrasound Medicine, Jingzhou Central Hospital, Jingzhou Hospital Affiliated to Yangtze university, Jingzhou 434020, Hubei Province, China
Xi-Yan Chen, Department of Medicine Imaging, The First People’s Hospital of Fuzhou City, Fuzhou 344000, Jiangxi Province, China
Le-Le Nie, Department of General Surgery, The First People’s Hospital of Fuzhou City, Fuzhou 344000, Jiangxi Province, China
Co-first authors: Sheng-Hu Zhang and Wan Li.
Author contributions: Zhang SH designed the research study; Li W, Chen XY performed the research; Nie LL conducted experiments, analyzed the data; All authors contributed to editorial changes in the manuscript, read and approved the final manuscript.
Institutional review board statement: This study was approved by the ethics committee of the First People’s Hospital of Fuzhou City (No. FZ202103).
Clinical trial registration statement: This trial was not registered. The local IRB was aware of the trial and approved study.
Informed consent statement: Informed consent was obtained from all study participants.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Le-Le Nie, Chief Physician, Department of General Surgery, The First People’s Hospital of Fuzhou City, No. 1099 Yingbin Avenue, Fuzhou 344000, Jiangxi Province, China. nielele520@163.com
Received: December 20, 2024 Revised: January 12, 2025 Accepted: February 7, 2025 Published online: April 15, 2025 Processing time: 95 Days and 8.6 Hours
Abstract
BACKGROUND
Gastric cancer is one of the most common malignant tumors worldwide, with its incidence and mortality rates ranking among the highest in gastrointestinal cancers. The overexpression or gene amplification of human epidermal growth factor receptor 2 (HER-2) occurs in approximately 15%-20% of gastric cancers and serves as a critical molecular target influencing prognosis and treatment outcomes. For patients with HER-2-positive gastric cancer, trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment. However, despite the demonstrated clinical benefits in prolonging survival, the overall efficacy remains limited. In recent years, with the successful application of immune checkpoint inhibitors (ICIs) in various malignant tumors, combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer. Nevertheless, the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.
AIM
To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.
METHODS
Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed. Patients were divided into a control group (n = 54, treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen) and an observation group (n = 50, treated with ICIs in addition to the standard regimen). The therapeutic efficacy, survival outcomes, and adverse reactions were compared between the two groups. Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.
RESULTS
With a median follow-up time of 14.6 months, there were no significant differences between the two groups in terms of objective response rate or disease control rate (P > 0.05). The median progression-free survival (mPFS) and mPFS for patients with immunohistochemistry 3 + in the observation group were significantly higher than those in the control group (P < 0.05). Among patients in the observation group, those with positive programmed death-ligand 1 (PD-L1) expression had a significantly higher mPFS than those with negative PD-L1 expression (P < 0.05). Regarding adverse events, significant differences were observed between the two groups in hypothyroidism and neutropenia (P < 0.05). Cox multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance status, peritoneal metastasis, positive programmed death-1 expression, and treatment regimen were independent factors influencing PFS (hazard ratio > 1, P < 0.05).
CONCLUSION
ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy, significantly prolonging PFS with manageable safety. ECOG performance status, peritoneal metastasis, positive PD-L1 expression, and treatment regimen are independent factors influencing PFS, warranting increased clinical attention to patients exhibiting these factors.
