Cargando…
The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis
SIMPLE SUMMARY: Proton pump inhibitors (PPIs) are the most commonly used gastric acid suppressants in cancer patients. However, long-term use of PPIs can cause dysbiosis effects disrupting gut microbiota with subsequent impairment of the effectiveness of immune checkpoint inhibitors (ICIs). Our stud...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818995/ https://www.ncbi.nlm.nih.gov/pubmed/36612290 http://dx.doi.org/10.3390/cancers15010284 |
_version_ | 1784865122336899072 |
---|---|
author | Chang, Yu Lin, Wan-Ying Chang, Yu-Cheng Huang, Chin-Hsuan Tzeng, Huey-En Abdul-Lattif, Eahab Wang, Tsu-Hsien Tseng, Tzu-Hsuan Kang, Yi-No Chi, Kuan-Yu |
author_facet | Chang, Yu Lin, Wan-Ying Chang, Yu-Cheng Huang, Chin-Hsuan Tzeng, Huey-En Abdul-Lattif, Eahab Wang, Tsu-Hsien Tseng, Tzu-Hsuan Kang, Yi-No Chi, Kuan-Yu |
author_sort | Chang, Yu |
collection | PubMed |
description | SIMPLE SUMMARY: Proton pump inhibitors (PPIs) are the most commonly used gastric acid suppressants in cancer patients. However, long-term use of PPIs can cause dysbiosis effects disrupting gut microbiota with subsequent impairment of the effectiveness of immune checkpoint inhibitors (ICIs). Our study demonstrates that, in advanced non-small cell lung cancer and urothelial carcinoma, patients receiving ICIs with concomitant PPIs are associated with poorer survival outcomes, when compared not only with those without PPIs but also with patients treated with chemotherapy, implying that PPIs could compromise the effectiveness of ICIs, causing them to be less effective than chemotherapy. As a result, we suggest that clinicians should avoid unnecessary PPI prescription in these patients. Conversely, there is little survival association with PPI in patients with melanoma, renal cell carcinoma, hepatocellular carcinoma, and squamous cell carcinoma of the neck and head. Nevertheless, future high quality prospective studies including more cancer types are warranted. ABSTRACT: (1) Although emerging evidence suggests that proton pump inhibitor (PPI)-induced dysbiosis negatively alters treatment response to immune checkpoint inhibitors (ICIs) in cancer patients, no study systematically investigates the association between PPIs, ICIs, and chemotherapy; (2) Cochrane Library, Embase, Medline, and PubMed were searched from inception to 20 May 2022, to identify relevant studies involving patients receiving ICIs or chemotherapy and reporting survival outcome between PPI users and non-users. Survival outcomes included overall survival (OS) and progression-free survival (PFS). Network meta-analyses were performed using random-effects models. p-scores, with a value between 0 and 1, were calculated to quantify the treatment ranking, with a higher score suggesting a higher probability of greater effectiveness. We also conducted pairwise meta-analyses of observational studies to complement our network meta-analysis; (3) We identified 62 studies involving 26,484 patients (PPI = 8834; non-PPI = 17,650), including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), melanoma, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and squamous cell carcinoma (SCC) of the neck and head. Eight post-hoc analyses from 18 randomized–controlled trials were included in our network, which demonstrated that, in advanced NSCLC and UC, patients under ICI treatment with concomitant PPI (p-score: 0.2016) are associated with both poorer OS (HR, 1.49; 95% CI, 1.37 to 1.67) and poorer PFS (HR, 1.41; 95% CI, 1.25 to 1.61) than those without PPIs (p-score: 1.000). Patients under ICI treatment with concomitant PPI also had poorer OS (HR, 1.18; 95% CI, 1.07 to 1.31) and poorer PFS (HR, 1.30; 95% CI, 1.14 to 1.48) in comparison with those receiving chemotherapy (p-score: 0.6664), implying that PPIs may compromise ICI’s effectiveness, making it less effective than chemotherapy. Our pairwise meta-analyses also supported this association. Conversely, PPI has little effect on patients with advanced melanoma, RCC, HCC, and SCC of the neck and head who were treated with ICIs; (4) “PPI-induced dysbiosis” serves as a significant modifier of treatment response in both advanced NSCLC and UC that are treated with ICIs, compromising the effectiveness of ICIs to be less than that of chemotherapy. Thus, clinicians should avoid unnecessary PPI prescription in these patients. “PPI-induced dysbiosis”, on the other hand, does not alter the treatment response to ICIs in advanced melanoma, RCC, HCC, and SCC of the head and neck. |
format | Online Article Text |
id | pubmed-9818995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98189952023-01-07 The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis Chang, Yu Lin, Wan-Ying Chang, Yu-Cheng Huang, Chin-Hsuan Tzeng, Huey-En Abdul-Lattif, Eahab Wang, Tsu-Hsien Tseng, Tzu-Hsuan Kang, Yi-No Chi, Kuan-Yu Cancers (Basel) Systematic Review SIMPLE SUMMARY: Proton pump inhibitors (PPIs) are the most commonly used gastric acid suppressants in cancer patients. However, long-term use of PPIs can cause dysbiosis effects disrupting gut microbiota with subsequent impairment of the effectiveness of immune checkpoint inhibitors (ICIs). Our study demonstrates that, in advanced non-small cell lung cancer and urothelial carcinoma, patients receiving ICIs with concomitant PPIs are associated with poorer survival outcomes, when compared not only with those without PPIs but also with patients treated with chemotherapy, implying that PPIs could compromise the effectiveness of ICIs, causing them to be less effective than chemotherapy. As a result, we suggest that clinicians should avoid unnecessary PPI prescription in these patients. Conversely, there is little survival association with PPI in patients with melanoma, renal cell carcinoma, hepatocellular carcinoma, and squamous cell carcinoma of the neck and head. Nevertheless, future high quality prospective studies including more cancer types are warranted. ABSTRACT: (1) Although emerging evidence suggests that proton pump inhibitor (PPI)-induced dysbiosis negatively alters treatment response to immune checkpoint inhibitors (ICIs) in cancer patients, no study systematically investigates the association between PPIs, ICIs, and chemotherapy; (2) Cochrane Library, Embase, Medline, and PubMed were searched from inception to 20 May 2022, to identify relevant studies involving patients receiving ICIs or chemotherapy and reporting survival outcome between PPI users and non-users. Survival outcomes included overall survival (OS) and progression-free survival (PFS). Network meta-analyses were performed using random-effects models. p-scores, with a value between 0 and 1, were calculated to quantify the treatment ranking, with a higher score suggesting a higher probability of greater effectiveness. We also conducted pairwise meta-analyses of observational studies to complement our network meta-analysis; (3) We identified 62 studies involving 26,484 patients (PPI = 8834; non-PPI = 17,650), including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), melanoma, renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and squamous cell carcinoma (SCC) of the neck and head. Eight post-hoc analyses from 18 randomized–controlled trials were included in our network, which demonstrated that, in advanced NSCLC and UC, patients under ICI treatment with concomitant PPI (p-score: 0.2016) are associated with both poorer OS (HR, 1.49; 95% CI, 1.37 to 1.67) and poorer PFS (HR, 1.41; 95% CI, 1.25 to 1.61) than those without PPIs (p-score: 1.000). Patients under ICI treatment with concomitant PPI also had poorer OS (HR, 1.18; 95% CI, 1.07 to 1.31) and poorer PFS (HR, 1.30; 95% CI, 1.14 to 1.48) in comparison with those receiving chemotherapy (p-score: 0.6664), implying that PPIs may compromise ICI’s effectiveness, making it less effective than chemotherapy. Our pairwise meta-analyses also supported this association. Conversely, PPI has little effect on patients with advanced melanoma, RCC, HCC, and SCC of the neck and head who were treated with ICIs; (4) “PPI-induced dysbiosis” serves as a significant modifier of treatment response in both advanced NSCLC and UC that are treated with ICIs, compromising the effectiveness of ICIs to be less than that of chemotherapy. Thus, clinicians should avoid unnecessary PPI prescription in these patients. “PPI-induced dysbiosis”, on the other hand, does not alter the treatment response to ICIs in advanced melanoma, RCC, HCC, and SCC of the head and neck. MDPI 2022-12-31 /pmc/articles/PMC9818995/ /pubmed/36612290 http://dx.doi.org/10.3390/cancers15010284 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Systematic Review Chang, Yu Lin, Wan-Ying Chang, Yu-Cheng Huang, Chin-Hsuan Tzeng, Huey-En Abdul-Lattif, Eahab Wang, Tsu-Hsien Tseng, Tzu-Hsuan Kang, Yi-No Chi, Kuan-Yu The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis |
title | The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis |
title_full | The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis |
title_fullStr | The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis |
title_full_unstemmed | The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis |
title_short | The Association between Baseline Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Chemotherapy: A Systematic Review with Network Meta-Analysis |
title_sort | association between baseline proton pump inhibitors, immune checkpoint inhibitors, and chemotherapy: a systematic review with network meta-analysis |
topic | Systematic Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818995/ https://www.ncbi.nlm.nih.gov/pubmed/36612290 http://dx.doi.org/10.3390/cancers15010284 |
work_keys_str_mv | AT changyu theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT linwanying theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT changyucheng theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT huangchinhsuan theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT tzenghueyen theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT abdullattifeahab theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT wangtsuhsien theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT tsengtzuhsuan theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT kangyino theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT chikuanyu theassociationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT changyu associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT linwanying associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT changyucheng associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT huangchinhsuan associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT tzenghueyen associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT abdullattifeahab associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT wangtsuhsien associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT tsengtzuhsuan associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT kangyino associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis AT chikuanyu associationbetweenbaselineprotonpumpinhibitorsimmunecheckpointinhibitorsandchemotherapyasystematicreviewwithnetworkmetaanalysis |