Meta-Analysis
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2020; 12(11): 1346-1363
Published online Nov 15, 2020. doi: 10.4251/wjgo.v12.i11.1346
Efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in treatment of advanced gastric cancer or gastroesophageal junction cancer: A meta-analysis
Li Yang, Xian-Zhe Dong, Xiao-Xuan Xing, Xiao-Hui Cui, Lin Li, Lan Zhang
Li Yang, Xian-Zhe Dong, Xiao-Xuan Xing, Xiao-Hui Cui, Lin Li, Lan Zhang, Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China
Li Yang, College of Pharmacy, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
Author contributions: Yang L and Dong XZ designed the study and wrote the manuscript; Yang L and Xing XX conducted the literature search; Yang L and Dong XZ collected and retrieved the data; Yang L and Cui XH analyzed the data; Dong XZ, Li L, and Zhang L critically reviewed and revised the manuscript; and all authors proofread the manuscript.
Supported by Beijing Hospitals Authority Ascent Plan, No. DFL20190803; Capital Science and Technology Leading Talent Training Project, No. Z191100006119017; National Nature and Science Foundation of China, No. 81773778; and China Postdoctoral Science Foundation, No. 2019M650775.
Conflict-of-interest statement: No conflict of interest.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lan Zhang, PhD, Professor, Department of Pharmacy, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing Engineering Research Center for Nervous System Drugs, Beijing Institute for Brain Disorders, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, No. 45 Changchun Street, Xicheng District, Beijing 100053, China. lanizhg@126.com
Received: June 9, 2020
Peer-review started: June 9, 2020
First decision: July 4, 2020
Revised: July 15, 2020
Accepted: September 18, 2020
Article in press: September 18, 2020
Published online: November 15, 2020
Processing time: 155 Days and 21.2 Hours
Abstract
BACKGROUND

Faced with limited and inadequate treatment options for patients with advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC), researchers have turned toward, with the support of promising clinical trials, anti-PD-1/anti-PD-L1 antibody therapy. But there are also different clinical trial results. To better assess its efficacy and safety, we integrated data from 13 eligible studies for a systematic review and meta-analysis.

AIM

To comprehensively evaluate the efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in the treatment of advanced GC/GEJC patients.

METHODS

PubMed, Web of Science, Cochrane Library ,and EMBASE databases were searched to identify eligible articles with outcomes including objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of anti-PD-1/anti-PD-L1 antibody therapy.

RESULTS

Our study encompassed a total of 13 trials totaling 1618 patients. The outcomes showed a pooled ORR and DCR of 15% (95% confidence interval [CI]: 14%-18%) and 40% (95%CI: 33%-46%), respectively. The pooled 6-mo OS and PFS were 54% (95%CI: 45%-64%) and 26% (95%CI: 20%-32%), respectively, and the 12-mo OS and PFS were 42% (95%CI: 21%-62%) and 11% (95%CI: 8%-13%), respectively. In addition, the incidence of any-grade AEs and grade ≥ 3 AEs was 64% (95%CI: 54%-73%) and 18% (95%CI: 16%-20%), respectively. Most importantly, PD-L1 positive patients exhibited a higher ORR rate than PD-L1 negative patients (odds ratio = 2.54, 95%CI: 1.56-4.15).

CONCLUSION

Anti-PD-1/anti-PD-L1 antibody therapy has shown promising anti-tumor efficacy with manageable AEs in advanced GC/GEJC patients, with PD-L1 overexpressing patients exhibiting a higher ORR. What is more, the clinical efficacy of anti-PD-1/PD-L1 combined with traditional chemotherapy drugs is even better, although the occurrence of AEs still causes considerate concerns.

Keywords: Gastric cancer; Gastroesophageal junction cancer; Anti-PD-1/anti-PD-L1 antibody therapy; Meta-analysis; Systematic review

Core Tip: Anti-PD-1/anti-PD-L1 antibody therapy, such as nivolumab and pembrolizumab, which has been approved by the FDA for marketing, enhances the body′s cellular immune response to anti-tumor effects by regulating T cell function. At present, it has become the first-line treatment for extensive stage small cell lung cancer and other cancers. In recent years, some clinical trials have also shown that anti-PD-1/anti-PD-L1 antibody therapy has a reliable effect in advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC) patients, but there is still controversy. The main purpose of this meta-analysis was to comprehensively evaluate the efficacy and safety of anti-PD-1/anti-PD-L1 antibody therapy in the treatment of advanced GC/GEJC patients.