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©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Effectiveness and tolerability of programmed cell death protein-1 inhibitor + chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers
Xiao-Min Zhang, Ting Yang, Ying-Ying Xu, Bao-Zhong Li, Wei Shen, Wen-Qing Hu, Cai-Wen Yan, Liang Zong
Xiao-Min Zhang, Ting Yang, Liang Zong, Department of Central Laboratory, Changzhi People’s Hospital, The Affiliated Hospital of Changzhi Medical College, Changzhi 046000, Shanxi Province, China
Ying-Ying Xu, Department of Gastrointestinal Surgery, Yizheng People’s Hospital, The Affiliated Hospital of Yangzhou University, Yangzhou 225000, Jiangsu Province, China
Bao-Zhong Li, Department of General Surgery, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
Wei Shen, Department of General Surgery, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, Jiangsu Province, China
Wen-Qing Hu, Liang Zong, Department of Gastrointestinal Surgery, Changzhi People’s Hospital, The Affiliated Hospital of Changzhi Medical College, Changzhi 046000, Shanxi Province, China
Cai-Wen Yan, Department of Gastroenterology, Changzhi People’s Hospital, The Affiliated Hospital of Changzhi Medical College, Changzhi 046000, Shanxi Province, China
Co-first authors: Xiao-Min Zhang and Ting Yang.
Author contributions: Zhang XM and Yang T contributed equally to this work. Zhang XM, Yang T, and Xu YY contributed to the acquisition, analysis and interpretation of data, and manuscript drafting; Zhang XM and Yang T revised the manuscript; Li BZ, Shen W, Hu WQ, and Yan CW were involved in the drafting and critical appraisal of manuscript; Zong L participated in the study design, data interpretation, final approval of the manuscript; and all authors have given final approval to this version of the manuscript to be published.
Supported by the Wu Jieping Medical Foundation, No. 320.6750.2020-11-5; the Health Commission of Shanxi Province, No. 2020130; and the Resource and Social Security of Shanxi Province, No. 20220056.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Liang Zong, PhD, Doctor, Department of Central Laboratory, Changzhi People’s Hospital, The Affiliated Hospital of Changzhi Medical College, No. 502 Changxing Middle Road, Luzhou District, Changzhi 046000, Shanxi Province, China. 250537471@qq.com
Received: September 21, 2023
Peer-review started: September 21, 2023
First decision: December 19, 2023
Revised: December 27, 2023
Accepted: February 22, 2024
Article in press: February 22, 2024
Published online: April 15, 2024
ARTICLE HIGHLIGHTS
Research background
Programmed cell death protein-1 (PD-1) inhibitor has shown effective anti-tumor immune activity by blocking the interaction of PD-1 with programmed death ligand 1 (PD-L1), and it combined with chemotherapy has been approved as a standard first- or second-line treatment option for patients with gastric cancer, gastroesophageal junction (GEJ) cancer and advanced esophageal cancer.
Research motivation
Several clinical trials of PD-1 inhibitors combined with chemotherapy vs chemotherapy alone have been completed or are ongoing. However, in terms of efficacy, it is controversial whether PD-1 inhibitor plus chemotherapy can significantly prolong patients’ overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone.
Research objectives
To compare the efficacy and safety of PD-1 inhibitor combined with chemotherapy and chemotherapy alone, and provide treatment options for patients with advanced gastric cancer, GEJ cancer and advanced esophageal cancer.
Research methods
We searched PubMed and Embase databases for clinical trials comparing the efficacy and safety of PD-1 inhibitors combined with chemotherapy and chemotherapy alone in gastric cancer, GEJ tumors, and esophageal cancer. The effect value of OS, PFS, objective response rate and adverse events were combined using random or fixed effects models. The significance of the pooled odds ratio or hazard ratio was assessed using the Z-test. We used the χ2-based Q-test and the I2 test to evaluate the heterogeneity between studies. Funnel plots were generated to assess the presence of publication bias in the outcomes. Additionally, sensitivity analyses were conducted to assess the stability of the results.
Research results
A total of 9 clinical trials were included in this study. Compared with the chemotherapy group, the PD-1 inhibitor + chemotherapy group had longer OS and PFS, and more patients achieved objective response rates. In addition, the number of adverse reactions in the combined treatment group was higher than that in the chemotherapy group alone. The results of subgroup analysis showed that compared with the subgroup of combined positive score (CPS) ≥ 1, patients in the CPS ≥ 5 and CPS ≥ 10 subgroups were able to achieve better therapeutic outcomes with PD-1 inhibitor combined with chemotherapy.
Research conclusions
The efficacy of PD-1 inhibitor combined with chemotherapy was superior to the chemotherapy group alone in patients with gastric cancer, GEJ tumors, and esophageal cancer. Subgroups with PD-L1 CPS ≥ 5 and ≥ 10 were more likely to benefit from PD-1 inhibitor combined with chemotherapy.
Research perspectives
Our findings provide reference for the treatment of patients with advanced gastric cancer, GEJ tumors, and advanced esophageal cancer. Therefore, our next step is to conduct a randomized controlled trial of PD-1 inhibitors combined with chemotherapy for gastric cancer and GEJ tumors to further improve the management of these patients.
