Basic StudyEffect of Antacid Use on Immune Checkpoint Inhibitors in Advanced Solid Cancer Patients: A Systematic Review and Meta-analysisDeng, Ruiyi*,†; Zhang, Hua*; Li, Yuan‡; Shi, Yanyan* Author Information *Peking University Third Hospital, Research Center of Clinical Epidemiology †Peking University Health Science Center ‡Department of Gastroenterology, Peking University Third Hospital, Beijing, P.R. China R.D. and H.Z. contributed equally. Supported by grants from National Natural Science Foundation of China (81700496) and Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation (BMU2021PY002). R.D. and H.Z. searched the literature and wrote the manuscript. Y.S. and Y.L. designed this study and revised the manuscript. Reprints: Yanyan Shi, Peking University Third Hospital, Beijing, P.R. China (e-mail: [email protected]); Yuan Li, Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, P.R. China (e-mail: [email protected]). Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.immunotherapy-journal.com. Journal of Immunotherapy ():10.1097/CJI.0000000000000442, October 19, 2022. | DOI: 10.1097/CJI.0000000000000442 Buy SDC PAP Metrics Abstract The influence of antacids use on immune checkpoint inhibitor (ICI) efficacy remains unclear. A systematic review and meta-analysis was performed to evaluate the effect of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) on ICI efficacy in advanced solid cancer patients. A systematic literature search in PubMed, EMBASE, and Web of Science was performed to retrieve studies investigating the effect of antacid use on ICI efficacy. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse events were measured using hazard ratios (HRs) or odds ratios (ORs). Thirty studies enrolling 16,147 advanced cancer patients receiving ICI treatment were included. The pooled analysis indicated that PPI use was associated with shorter OS (HR=1.40, 95% CI, 1.25–1.57) and PFS (HR=1.34, 95% CI, 1.19–1.52) in advanced cancer patients treated with ICIs. PPI use did not show effect on ORR or immune-related adverse event of advanced cancer patients receiving ICI treatment. OS, PFS, and ORR did not differ between H2RA users and non-H2RA users. In subgroup analyses, PPI use was associated with shorter OS and PFS in NSCLC and urothelial carcinoma patients and in patients treated with anti–programmed cell death 1 or anti–programmed cell death ligand 1 monotherapy. In addition, ICI efficacy was different in the antacid exposure time frame subgroups. In conclusion, PPI use has a negative effect on OS and PFS among advanced cancer patients receiving ICI treatment. PPIs should be cautiously administered among advanced cancer patients treated with ICI. The safety of H2RAs and the influence of H2RAs on ICI efficacy need further investigation. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.