Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jul 26, 2021; 9(21): 5782-5793
Published online Jul 26, 2021. doi: 10.12998/wjcc.v9.i21.5782
Research status on immunotherapy trials of gastric cancer
Chao Liang, Heng-Miao Wu, Wei-Ming Yu, Wei Chen
Chao Liang, Wei-Ming Yu, Department of General Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo 315040, Zhejiang Province, China
Heng-Miao Wu, Ningbo Medical Center Lihuili Hospital, Ningbo University, Ningbo 315040, Zhejiang Province, China
Wei Chen, Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
Author contributions: Liang C and Wu HM drafted the manuscript; Yu WM and Chen W collected the data and revised the manuscript.
Supported by National Natural Science Funds of Young Scientists of China, No. 81802944; Zhejiang Provincial Public Welfare Technology Application Research Project, No. LGF18H160007; Program of Ningbo Medical Research Center for Digestive System Cancer, No. 2019A21003; Zhejiang Provincial Natural Science Foundation, No. LR20H160001; Zhejiang Provincial Ten Thousand Plan for Young Top Talents to Wei Chen (2018); Training Objects of Health Innovative Talents of Zhejiang Health to Wei Chen (2018); Key Project Co-constructed by Zhejiang Province and Ministry, No. WKJ-ZJ-1916; National Natural Science Foundation of China, No. 81972693, No. 81802383, No. 81972674, No. 81673809, and No. 31900543; Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project, No. 2020ZZ004; and Projects of Lishui Key Research and Development Plan in Zhejiang Province, No. 2017ZDYF12.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
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:
Corresponding author: Wei Chen, MD, PhD, Doctor, Professor, Surgeon, Cancer Institute of Integrated Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, No. 234 Gucui Road, Hangzhou 310012, Zhejiang Province, China.
Received: February 10, 2021
Peer-review started: February 10, 2021
First decision: March 30, 2021
Revised: April 13, 2021
Accepted: May 25, 2021
Article in press: May 25, 2021
Published online: July 26, 2021

The breakthrough of immune checkpoint inhibitor (ICI) therapy has created extensive opportunities for cancer immunotherapy. Especially, the block of programmed death-1/programmed death ligand 1 (PD-L1) axis using ICIs has become a new therapeutic strategy to treat advanced gastric cancer (GC). However, in the past decade, single-arm and randomized trials for single-drug ICI therapy showed that the therapeutic effect was not satisfactory, including clinical trials for advanced GC. However, after selecting suitable predictive biomarkers and developing a combination of anti-angiogenic targeted drugs and other chemotherapeutic drugs, the objective response rate and progression-free survival of patients with gastric cancer were improved significantly. The United States Food and Drug Administration has approved treatment with pembrolizumab for patients with advanced GC with PD-L1 expression or microsatellite instability-high/mismatch repair deficiency. In this review, the updated data from the latest trial results of combination immunotherapy for GC are presented. Based on the outcome of combination therapy, we discuss its possible molecular mechanism and summarize effective predictive biomarkers. We also discuss possible problems stemming from results of other clinical trials of ICI treatment and propose other directions for ICI therapy.

Keywords: Gastric cancer, Immunotherapy, Clinical trial, Immune checkpoint inhibitor, Neoadjuvant therapy

Core Tip: Immune checkpoint inhibitors gigantically expand the methods of immunotherapy and bring a glimmer of hopefulness for patients with advanced gastric cancer (GC). Ongoing clinical trials show that the effect of monotherapy was not satisfactory, while the combination therapy manifested a better response rate. The most recent clinical trial results of GC immunotherapy are reviewed to suggest the reasons and mechanisms of the high response rate. Additionally, we propose the potential problems of these trials and speculate on the benefits of immune checkpoint inhibitors in neoadjuvant therapy.