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Volume 12
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Systematic Review

The Impact of Concomitant Proton Pump Inhibitors on Immunotherapy Efficacy among Patients with Urothelial Carcinoma: A Meta-Analysis

by
Alessandro Rizzo
1,*,
Matteo Santoni
2,
Veronica Mollica
3,
Angela Dalia Ricci
4,
Concetta Calabrò
5,
Antonio Cusmai
1,
Gennaro Gadaleta-Caldarola
6,
Gennaro Palmiotti
1,† and
Francesco Massari
3,7,†
1
Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, Viale Orazio Flacco 65, 70124 Bari, Italy
2
Oncology Unit, Macerata Hospital, 62100 Macerata, Italy
3
Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138 Bologna, Italy
4
Departmental Unit of Medical Oncology, ‘San Paolo’ Hospital, ASL BA, 70123 Bari, Italy
5
S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo-Bari, 70124 Bari, Italy
6
Medical Oncology Unit, ‘Mons. R. Dimiccoli’ Hospital, Azienda Sanitaria Locale Barletta, 76121 Barletta, Italy
7
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
J. Pers. Med. 2022, 12(5), 842; https://doi.org/10.3390/jpm12050842
Submission received: 28 April 2022 / Revised: 17 May 2022 / Accepted: 19 May 2022 / Published: 20 May 2022
(This article belongs to the Special Issue Precision Medicine and Molecular Diagnosis for Urogenital Cancer)
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Abstract

Background. Immune checkpoint inhibitors (ICIs) have recently represented a breakthrough in urothelial carcinoma (UC). Proton pump inhibitors (PPIs) are routinely used for extended time periods in UC patients, with these agents having potentially and frequently undervalued effects on ICIs efficacy. Methods. We performed a meta-analysis aimed at investigating the impact of concomitant PPI administration on progression-free survival (PFS) and overall survival (OS) among patients receiving immunotherapy for metastatic UC. Results. Two studies encompassing a total of 1015 patients were included. The pooled Hazard Ratios (HRs) for OS and PFS were 1.55 (95% CI, 1.31–1.84) and 1.43 (95% CI, 1.23–1.66), respectively, suggesting that the administration of PPIs was negatively associated with PFS and with OS in UC patients treated with ICIs. Conclusions. The current meta-analysis represents the first study to provide a systematic evaluation of the impact of concomitant PPI use in UC patients treated with ICIs. Further studies are warranted on this topic to clarify the relationship between gut microbiome, antiacid exposure, and cancer immunotherapy. In the current era of medical oncology, progress in this setting will require the collaboration of basic science and clinical research to optimize systemic treatment and to improve the outcomes of UC patients receiving ICIs.
Keywords: atezolizumab; durvalumab; immunotherapy; meta-analysis; nivolumab; pembrolizumab; proton pump inhibitors; urothelial carcinoma atezolizumab; durvalumab; immunotherapy; meta-analysis; nivolumab; pembrolizumab; proton pump inhibitors; urothelial carcinoma

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MDPI and ACS Style

Rizzo, A.; Santoni, M.; Mollica, V.; Ricci, A.D.; Calabrò, C.; Cusmai, A.; Gadaleta-Caldarola, G.; Palmiotti, G.; Massari, F. The Impact of Concomitant Proton Pump Inhibitors on Immunotherapy Efficacy among Patients with Urothelial Carcinoma: A Meta-Analysis. J. Pers. Med. 2022, 12, 842. https://doi.org/10.3390/jpm12050842

AMA Style

Rizzo A, Santoni M, Mollica V, Ricci AD, Calabrò C, Cusmai A, Gadaleta-Caldarola G, Palmiotti G, Massari F. The Impact of Concomitant Proton Pump Inhibitors on Immunotherapy Efficacy among Patients with Urothelial Carcinoma: A Meta-Analysis. Journal of Personalized Medicine. 2022; 12(5):842. https://doi.org/10.3390/jpm12050842

Chicago/Turabian Style

Rizzo, Alessandro, Matteo Santoni, Veronica Mollica, Angela Dalia Ricci, Concetta Calabrò, Antonio Cusmai, Gennaro Gadaleta-Caldarola, Gennaro Palmiotti, and Francesco Massari. 2022. "The Impact of Concomitant Proton Pump Inhibitors on Immunotherapy Efficacy among Patients with Urothelial Carcinoma: A Meta-Analysis" Journal of Personalized Medicine 12, no. 5: 842. https://doi.org/10.3390/jpm12050842

APA Style

Rizzo, A., Santoni, M., Mollica, V., Ricci, A. D., Calabrò, C., Cusmai, A., Gadaleta-Caldarola, G., Palmiotti, G., & Massari, F. (2022). The Impact of Concomitant Proton Pump Inhibitors on Immunotherapy Efficacy among Patients with Urothelial Carcinoma: A Meta-Analysis. Journal of Personalized Medicine, 12(5), 842. https://doi.org/10.3390/jpm12050842

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