Antacid exposure and immunotherapy outcomes among patients with advanced hepatocellular carcinoma

Tomi Jun; Umut Ozbek; Sirish Dharmapuri; Camille Hardy-Abeloos; Huili Zhu; Jung Yi Lin; Nicola Personeni; Tiziana Pressiani; Naoshi Nishida; Pei Chang Lee; Chieh Ju Lee; Hannah Hildebrand; Neil Nimkar; Sonal Paul; Petros Fessas; Muntaha Naeem; Dominik Bettinger; Uqba Khan; Anwaar Saeed; Yi Hsiang Huang; Masatoshi Kudo; Lorenza Rimassa; Thomas U. Marron; David J. Pinato; Celina Ang

doi:10.1177/17588359211010937

Antacid exposure and immunotherapy outcomes among patients with advanced hepatocellular carcinoma

Tomi Jun, Umut Ozbek, Sirish Dharmapuri, Camille Hardy-Abeloos, Huili Zhu, Jung Yi Lin, Nicola Personeni, Tiziana Pressiani, Naoshi Nishida, Pei Chang Lee, Chieh Ju Lee, Hannah Hildebrand, Neil Nimkar, Sonal Paul, Petros Fessas, Muntaha Naeem, Dominik Bettinger, Uqba Khan, Anwaar Saeed, Yi Hsiang HuangMasatoshi Kudo, Lorenza Rimassa, Thomas U. Marron, David J. Pinato, Celina Ang

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17 Scopus citations

Abstract

Background: Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting. Methods: We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs). Results: Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75–1.35) or multivariable analysis (HR 0.98, 95% CI 0.71–1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66–2.65) or AEs (OR 1.07, 95% CI 0.54–2.12) in multivariable analysis. Conclusions: Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.

Original language	English
Journal	Therapeutic Advances in Medical Oncology
Volume	13
DOIs	https://doi.org/10.1177/17588359211010937
State	Published - 2021

Keywords

antacid
hepatocellular carcinoma
immunotherapy
proton pump inhibitor

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Jun, T., Ozbek, U., Dharmapuri, S., Hardy-Abeloos, C., Zhu, H., Lin, J. Y., Personeni, N., Pressiani, T., Nishida, N., Lee, P. C., Lee, C. J., Hildebrand, H., Nimkar, N., Paul, S., Fessas, P., Naeem, M., Bettinger, D., Khan, U., Saeed, A., ... Ang, C. (2021). Antacid exposure and immunotherapy outcomes among patients with advanced hepatocellular carcinoma. Therapeutic Advances in Medical Oncology, 13. https://doi.org/10.1177/17588359211010937

@article{5135d4196eef4c00baf19402247c6889,

title = "Antacid exposure and immunotherapy outcomes among patients with advanced hepatocellular carcinoma",

abstract = "Background: Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting. Methods: We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs). Results: Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75–1.35) or multivariable analysis (HR 0.98, 95% CI 0.71–1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66–2.65) or AEs (OR 1.07, 95% CI 0.54–2.12) in multivariable analysis. Conclusions: Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.",

keywords = "antacid, hepatocellular carcinoma, immunotherapy, proton pump inhibitor",

author = "Tomi Jun and Umut Ozbek and Sirish Dharmapuri and Camille Hardy-Abeloos and Huili Zhu and Lin, {Jung Yi} and Nicola Personeni and Tiziana Pressiani and Naoshi Nishida and Lee, {Pei Chang} and Lee, {Chieh Ju} and Hannah Hildebrand and Neil Nimkar and Sonal Paul and Petros Fessas and Muntaha Naeem and Dominik Bettinger and Uqba Khan and Anwaar Saeed and Huang, {Yi Hsiang} and Masatoshi Kudo and Lorenza Rimassa and Marron, {Thomas U.} and Pinato, {David J.} and Celina Ang",

note = "Publisher Copyright: {\textcopyright} The Author(s), 2021.",

year = "2021",

doi = "10.1177/17588359211010937",

language = "English",

volume = "13",

journal = "Therapeutic Advances in Medical Oncology",

issn = "1758-8340",

publisher = "SAGE Publications Inc.",

}

Jun, T, Ozbek, U, Dharmapuri, S, Hardy-Abeloos, C, Zhu, H, Lin, JY, Personeni, N, Pressiani, T, Nishida, N, Lee, PC, Lee, CJ, Hildebrand, H, Nimkar, N, Paul, S, Fessas, P, Naeem, M, Bettinger, D, Khan, U, Saeed, A, Huang, YH, Kudo, M, Rimassa, L, Marron, TU, Pinato, DJ & Ang, C 2021, 'Antacid exposure and immunotherapy outcomes among patients with advanced hepatocellular carcinoma', Therapeutic Advances in Medical Oncology, vol. 13. https://doi.org/10.1177/17588359211010937

TY - JOUR

T1 - Antacid exposure and immunotherapy outcomes among patients with advanced hepatocellular carcinoma

AU - Jun, Tomi

AU - Ozbek, Umut

AU - Dharmapuri, Sirish

AU - Hardy-Abeloos, Camille

AU - Zhu, Huili

AU - Lin, Jung Yi

AU - Personeni, Nicola

AU - Pressiani, Tiziana

AU - Nishida, Naoshi

AU - Lee, Pei Chang

AU - Lee, Chieh Ju

AU - Hildebrand, Hannah

AU - Nimkar, Neil

AU - Paul, Sonal

AU - Fessas, Petros

AU - Naeem, Muntaha

AU - Bettinger, Dominik

AU - Khan, Uqba

AU - Saeed, Anwaar

AU - Huang, Yi Hsiang

AU - Kudo, Masatoshi

AU - Rimassa, Lorenza

AU - Marron, Thomas U.

AU - Pinato, David J.

AU - Ang, Celina

PY - 2021

Y1 - 2021

N2 - Background: Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting. Methods: We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs). Results: Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75–1.35) or multivariable analysis (HR 0.98, 95% CI 0.71–1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66–2.65) or AEs (OR 1.07, 95% CI 0.54–2.12) in multivariable analysis. Conclusions: Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.

AB - Background: Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting. Methods: We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs). Results: Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75–1.35) or multivariable analysis (HR 0.98, 95% CI 0.71–1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66–2.65) or AEs (OR 1.07, 95% CI 0.54–2.12) in multivariable analysis. Conclusions: Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.

KW - antacid

KW - hepatocellular carcinoma

KW - immunotherapy

KW - proton pump inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85105542522&partnerID=8YFLogxK

U2 - 10.1177/17588359211010937

DO - 10.1177/17588359211010937

M3 - Article

AN - SCOPUS:85105542522

SN - 1758-8340

VL - 13

JO - Therapeutic Advances in Medical Oncology

JF - Therapeutic Advances in Medical Oncology

ER -

Antacid exposure and immunotherapy outcomes among patients with advanced hepatocellular carcinoma

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Keywords

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