Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma

Background and Rationale: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC...

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Autores principales:	Petros Fessas, Muntaha Naeem, Matthias Pinter, Thomas U. Marron, David Szafron, Lorenz Balcar, Anwaar Saeed, Tomi Jun, Sirish Dharmapuri, Anuhya Gampa, Yinghong Wang, Uqba Khan, Mahvish Muzaffar, Musharraf Navaid, Pei-Chang Lee, Anushi Bulumulle, Bo Yu, Sonal Paul, Neil Nimkar, Dominik Bettinger, Hannah Hildebrand, Yehia I. Abugabal, Tiziana Pressiani, Nicola Personeni, Naoshi Nishida, Masatoshi Kudo, Ahmed Kaseb, Yi-Hsiang Huang, Celina Ang, Anjana Pillai, Lorenza Rimassa, Abdul Rafeh Naqash, Elad Sharon, Alessio Cortellini, David J. Pinato
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	antibiotics cancer immunotherapy immune checkpoint inhibitors hepatocellular carcinoma gut microbiota Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5b2616ec247c4eb78946d132559d4210
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spelling	oai:doaj.org-article:5b2616ec247c4eb78946d132559d42102021-11-04T14:40:32ZEarly Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma2235-17951664-555310.1159/000519108https://doaj.org/article/5b2616ec247c4eb78946d132559d42102021-10-01T00:00:00Zhttps://www.karger.com/Article/FullText/519108https://doaj.org/toc/2235-1795https://doaj.org/toc/1664-5553Background and Rationale: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. Methods: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. Results: Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (n = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank p = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, p = 0.0494). Conclusions: Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.Petros FessasMuntaha NaeemMatthias PinterThomas U. MarronDavid SzafronLorenz BalcarAnwaar SaeedTomi JunSirish DharmapuriAnuhya GampaYinghong WangUqba KhanMahvish MuzaffarMusharraf NavaidPei-Chang LeeAnushi BulumulleBo YuSonal PaulNeil NimkarDominik BettingerHannah HildebrandYehia I. AbugabalTiziana PressianiNicola PersoneniNaoshi NishidaMasatoshi KudoAhmed KasebYi-Hsiang HuangCelina AngAnjana PillaiLorenza RimassaAbdul Rafeh NaqashElad SharonAlessio CortelliniDavid J. PinatoKarger Publishersarticleantibioticscancer immunotherapyimmune checkpoint inhibitorshepatocellular carcinomagut microbiotaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLiver Cancer, Vol 10, Iss 6, Pp 583-592 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotics cancer immunotherapy immune checkpoint inhibitors hepatocellular carcinoma gut microbiota Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	antibiotics cancer immunotherapy immune checkpoint inhibitors hepatocellular carcinoma gut microbiota Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Petros Fessas Muntaha Naeem Matthias Pinter Thomas U. Marron David Szafron Lorenz Balcar Anwaar Saeed Tomi Jun Sirish Dharmapuri Anuhya Gampa Yinghong Wang Uqba Khan Mahvish Muzaffar Musharraf Navaid Pei-Chang Lee Anushi Bulumulle Bo Yu Sonal Paul Neil Nimkar Dominik Bettinger Hannah Hildebrand Yehia I. Abugabal Tiziana Pressiani Nicola Personeni Naoshi Nishida Masatoshi Kudo Ahmed Kaseb Yi-Hsiang Huang Celina Ang Anjana Pillai Lorenza Rimassa Abdul Rafeh Naqash Elad Sharon Alessio Cortellini David J. Pinato Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma
description	Background and Rationale: Immune checkpoint inhibitor (ICI) therapy is an expanding therapeutic option for hepatocellular carcinoma (HCC). Antibiotics (ATB) taken prior to or early during ICI therapy can impact immunotherapy efficacy across indications; however, the effect of ATB is undefined in HCC. Methods: In a large international cohort of 450 ICI recipients from Europe, North America, and Asia, we categorized patients according to timing of ATB focusing on exposure within −30 to +30 days from ICI (early immunotherapy period [EIOP]). EIOP was evaluated in association with overall survival (OS), progression-free survival (PFS), and best radiologic response using RECIST 1.1 criteria. Results: Our study comprised mostly cirrhotic (329, 73.3%) males (355, 79.1%) with a Child-Turcotte Pugh class of A (332, 73.9%), receiving ICI after 1 therapy line (251, 55.9%) for HCC of Barcelona clinic liver cancer stage C (325, 72.4%). EIOP (n = 170, 37.9%) was independent of baseline clinicopathologic features of HCC and correlated with longer PFS (6.1 vs. 3.7 months, log-rank p = 0.0135). EIOP+ patients had similar OS, overall response, and disease control rates (DCRs) compared to EIOP. The effect of EIOP persisted in landmark time analyses and in multivariable models, confirming the independent predictive role of EIOP in influencing PFS following adjustment for covariates reflective of tumor burden, liver function, and ICI regimen administered. In patients receiving programmed cell death-1 receptor/ligand inhibitors monotherapy, EIOP was also associated with higher DCRs (61.4% vs. 50.9%, p = 0.0494). Conclusions: Unlike other oncological indications, ATB in the 30 days before or after ICI initiation is associated with improved benefit from immunotherapy, independent of disease and treatment-related features. Evaluation of the immune microbiologic determinants of response to ICI in HCC warrants further investigation.
format	article
author	Petros Fessas Muntaha Naeem Matthias Pinter Thomas U. Marron David Szafron Lorenz Balcar Anwaar Saeed Tomi Jun Sirish Dharmapuri Anuhya Gampa Yinghong Wang Uqba Khan Mahvish Muzaffar Musharraf Navaid Pei-Chang Lee Anushi Bulumulle Bo Yu Sonal Paul Neil Nimkar Dominik Bettinger Hannah Hildebrand Yehia I. Abugabal Tiziana Pressiani Nicola Personeni Naoshi Nishida Masatoshi Kudo Ahmed Kaseb Yi-Hsiang Huang Celina Ang Anjana Pillai Lorenza Rimassa Abdul Rafeh Naqash Elad Sharon Alessio Cortellini David J. Pinato
author_facet	Petros Fessas Muntaha Naeem Matthias Pinter Thomas U. Marron David Szafron Lorenz Balcar Anwaar Saeed Tomi Jun Sirish Dharmapuri Anuhya Gampa Yinghong Wang Uqba Khan Mahvish Muzaffar Musharraf Navaid Pei-Chang Lee Anushi Bulumulle Bo Yu Sonal Paul Neil Nimkar Dominik Bettinger Hannah Hildebrand Yehia I. Abugabal Tiziana Pressiani Nicola Personeni Naoshi Nishida Masatoshi Kudo Ahmed Kaseb Yi-Hsiang Huang Celina Ang Anjana Pillai Lorenza Rimassa Abdul Rafeh Naqash Elad Sharon Alessio Cortellini David J. Pinato
author_sort	Petros Fessas
title	Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma
title_short	Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma
title_full	Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma
title_fullStr	Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma
title_full_unstemmed	Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma
title_sort	early antibiotic exposure is not detrimental to therapeutic effect from immunotherapy in hepatocellular carcinoma
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/5b2616ec247c4eb78946d132559d4210
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Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma

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