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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
BACKGROUND
The combination of programmed cell death protein-1 (PD-1) inhibitor and chemotherapy is approved as a standard first- or second-line treatment in patients with advanced oesophageal or gastric cancer. However, it is unclear whether this combination is superior to chemotherapy alone.
AIM
To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal carcinoma.
METHODS
We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer. We employed either random or fixed models to analyze the outcomes of each clinical trial, encompassing data on overall survival (OS), progression-free survival (PFS), objective response rate, and adverse events (AEs).
RESULTS
Nine phase 3 clinical trials (7016 advanced oesophageal and gastric cancer patients) met the inclusion criteria. Our meta-analysis demonstrated that the pooled PD-1 inhibitor + chemotherapy group had a significantly longer OS than the chemotherapy-alone group [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.71-0.81]; the pooled PFS result was consistent with that of OS (HR = 0.67, 95%CI: 0.61-0.74). The count of patients achieving an objective response in the PD-1 inhibitor + chemotherapy group surpassed that of the chemotherapy-alone group [odds ratio (OR) = 1.86, 95%CI: 1.59-2.18]. AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group, regardless of whether ≥ grade 3 only (OR = 1.30, 95%CI: 1.07-1.57) or all AE grades (OR = 1.88, 95%CI: 1.39-2.54) were examined. We performed a subgroup analysis based on the programmed death-ligand 1 (PD-L1) combined positive score (CPS) and noted extended OS and PFS durations within the CPS ≥ 1, CPS ≥ 5, and CPS ≥ 10 subgroups of the PD-1 inhibitor + chemotherapy group.
CONCLUSION
In contrast to chemotherapy alone, the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer, GEJ tumor, or oesophageal cancer. This holds true particularly for individuals with PD-L1 CPS scores of ≥ 5 and ≥ 10.
Core Tip: The combination of programmed cell death protein-1 (PD-1) inhibitor and chemotherapy is approved as a standard first- or second-line treatment in patients with advanced oesophageal or gastric cancer. However, it is unclear whether this combination is superior to chemotherapy alone. We assessed the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, or oesophageal carcinoma. Our analysis showed that immunotherapy combined with chemotherapy significantly prolonged patients’ overall survival and progression-free survival relative to the chemotherapy group, both in the overall population and in the combined positive score (CPS) ≥ 1, CPS ≥ 5, and CPS ≥ 10 subgroup.
