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Review
. 2022 Mar 9;14(6):1404.
doi: 10.3390/cancers14061404.

Impact of Proton Pump Inhibitors and Histamine-2-Receptor Antagonists on Non-Small Cell Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis

Alessandro Rizzo  1 , Antonio Cusmai  1 , Francesco Giovannelli  1 , Silvana Acquafredda  1 , Lucia Rinaldi  1 , Andrea Misino  1 , Elisabetta Sara Montagna  1 , Valentina Ungaro  2 , Mariagrazia Lorusso  3 , Gennaro Palmiotti  1
Affiliations
Review

Impact of Proton Pump Inhibitors and Histamine-2-Receptor Antagonists on Non-Small Cell Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis

Alessandro Rizzo et al. Cancers (Basel). .

Abstract

(1) Background: In recent years, immunotherapy has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), representing a therapeutic breakthrough in this field. Antacid agents such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are commonly prescribed for extended periods in NSCLC patients, and these drugs have the potential to modify the efficacy of immune checkpoint inhibitors (ICIs). (2) Materials and Methods: Herein, we conducted a systematic review and meta-analysis to investigate the impact of PPIs and H2RAs on progression-free survival (PFS) and overall survival (OS) among patients receiving immunotherapy for metastatic NSCLC. Effect measures for OS were Hazard Ratios (HRs) and 95% Confidence Intervals (CIs), which were extracted from available studies. Forest plots were used to assess HRs to describe the relationship between treatment and OS in the specified cohorts of patients. (3) Results: Six studies were included in the analysis, involving 2267 patients. The pooled HRs for OS and PFS were 1.4 (95% CI, 1.25-1.58) and 1.29 (95% CI, 1.17-1.43), respectively, suggesting that PPIs and H2RAs administration was negatively associated with PFS and OS. (4) Conclusion: Concomitant antacid use could modify the activity of ICIs in NSCLC patients.

Keywords: antiacid; immune checkpoint inhibitors; immunotherapy; non-small cell lung cancer; proton pump inhibitors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Selection of trials included in the meta-analysis according to PRISMA statement.
Figure 2
Figure 2
Forest plot of comparison between non-small cell lung cancer patients receiving immune checkpoint inhibitors with concomitant PPIs and/or H2RAs use or not; the outcome (ES) was Hazard Ratio of Overall Survival. Abbreviations: CI: confidence interval; ES: Effect Size (Hazard Ratio); W: Weight.
Figure 3
Figure 3
Forest plot of comparison between non-small cell lung cancer patients receiving immune checkpoint inhibitors with concomitant PPIs and/or H2RAs use or not; the outcome (ES) was Hazard Ratio of Progression-Free Survival. Abbreviations: CI: confidence interval; ES: Effect Size (Hazard Ratio); W: Weight.
Figure 4
Figure 4
Funnel plot of overall survival.
Figure 5
Figure 5
Funnel plot of progression-free survival.
See this image and copyright information in PMC

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