Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors
BackgroundIn patients with cirrhosis, portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, promoting an inflammatory state that can lead to the progression of liver disease and development of hepatocellular carcinoma (HCC). We aimed to investigate whether be...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1128569/full |
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| author | Y. Linda Wu Grace van Hyfte Umut Özbek Marlene Reincke Anuhya Gampa Yehia I. Mohamed Naoshi Nishida Brooke Wietharn Suneetha Amara Pei-Chang Lee Bernhard Scheiner Lorenz Balcar Matthias Pinter Arndt Vogel Arndt Weinmann Anwaar Saeed Anjana Pillai Lorenza Rimassa Lorenza Rimassa Abdul Rafeh Naqash Mahvish Muzaffar Yi-Hsiang Huang Ahmed O. Kaseb Masatoshi Kudo David J. Pinato Celina Ang |
| author_facet | Y. Linda Wu Grace van Hyfte Umut Özbek Marlene Reincke Anuhya Gampa Yehia I. Mohamed Naoshi Nishida Brooke Wietharn Suneetha Amara Pei-Chang Lee Bernhard Scheiner Lorenz Balcar Matthias Pinter Arndt Vogel Arndt Weinmann Anwaar Saeed Anjana Pillai Lorenza Rimassa Lorenza Rimassa Abdul Rafeh Naqash Mahvish Muzaffar Yi-Hsiang Huang Ahmed O. Kaseb Masatoshi Kudo David J. Pinato Celina Ang |
| author_sort | Y. Linda Wu |
| collection | DOAJ |
| description | BackgroundIn patients with cirrhosis, portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, promoting an inflammatory state that can lead to the progression of liver disease and development of hepatocellular carcinoma (HCC). We aimed to investigate whether beta blockers (BBs), which can mediate portal hypertension, conferred survival benefits in patients treated with immune checkpoint inhibitors (ICIs).MethodsWe conducted a retrospective, observational study of 578 patients with unresectable HCC treated with ICI from 2017 to 2019 at 13 institutions across three continents. BB use was defined as exposure to BBs at any time during ICI therapy. The primary objective was to assess the association of BB exposure with overall survival (OS). Secondary objectives were to evaluate the association of BB use with progression-free survival (PFS) and objective response rate (ORR) according to RECIST 1.1 criteria.ResultsIn our study cohort, 203 (35%) patients used BBs at any point during ICI therapy. Of these, 51% were taking a nonselective BB. BB use was not significantly correlated with OS (hazard ratio [HR] 1.12, 95% CI 0.9-1.39, P = 0.298), PFS (HR 1.02, 95% CI 0.83-1.26, P = 0.844) or ORR (odds ratio [OR] 0.84, 95% CI 0.54-1.31, P = 0.451) in univariate or multivariate analyses. BB use was also not associated with incidence of adverse events (OR 1.38, 95% CI 0.96-1.97, P = 0.079). Specifically, nonselective BB use was not correlated with OS (HR 0.94, 95% CI 0.66-1.33, P = 0.721), PFS (HR 0.92, 0.66-1.29, P = 0.629), ORR (OR 1.20, 95% CI 0.58-2.49, P = 0.623), or rate of adverse events (OR 0.82, 95% CI 0.46-1.47, P = 0.510).ConclusionIn this real-world population of patients with unresectable HCC treated with immunotherapy, BB use was not associated with OS, PFS or ORR. |
| first_indexed | 2024-04-10T15:17:08Z |
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| id | doaj.art-5885bcec7b444fc4b4fe6d9c281e9f99 |
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| language | English |
| last_indexed | 2024-04-10T15:17:08Z |
| publishDate | 2023-02-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-5885bcec7b444fc4b4fe6d9c281e9f992023-02-14T19:06:16ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-02-011310.3389/fonc.2023.11285691128569Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitorsY. Linda Wu0Grace van Hyfte1Umut Özbek2Marlene Reincke3Anuhya Gampa4Yehia I. Mohamed5Naoshi Nishida6Brooke Wietharn7Suneetha Amara8Pei-Chang Lee9Bernhard Scheiner10Lorenz Balcar11Matthias Pinter12Arndt Vogel13Arndt Weinmann14Anwaar Saeed15Anjana Pillai16Lorenza Rimassa17Lorenza Rimassa18Abdul Rafeh Naqash19Mahvish Muzaffar20Yi-Hsiang Huang21Ahmed O. Kaseb22Masatoshi Kudo23David J. Pinato24Celina Ang25Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, GermanySection of Gastroenterology, Hepatology and Nutrition, The University of Chicago Medical Center, Chicago, IL, United StatesDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, JapanDivision of Medical Oncology, Department of Medicine, Kansas University Cancer Center, Kansas City, KS, United StatesDivision of Hematology/Oncology, East Carolina University, Greenville, NC, United StatesDivision of Gastroenterology and Hepatology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan0Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria0Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria0Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany2Department of Internal Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyDivision of Medical Oncology, Department of Medicine, Kansas University Cancer Center, Kansas City, KS, United StatesSection of Gastroenterology, Hepatology and Nutrition, The University of Chicago Medical Center, Chicago, IL, United States3Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy4Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Clinical and Research Hospital, Rozzano (Milan), Italy5Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD, United StatesDivision of Hematology/Oncology, East Carolina University, Greenville, NC, United StatesDivision of Gastroenterology and Hepatology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, TaiwanDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United StatesDepartment of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan6Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital London, London, United KingdomDivision of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesBackgroundIn patients with cirrhosis, portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, promoting an inflammatory state that can lead to the progression of liver disease and development of hepatocellular carcinoma (HCC). We aimed to investigate whether beta blockers (BBs), which can mediate portal hypertension, conferred survival benefits in patients treated with immune checkpoint inhibitors (ICIs).MethodsWe conducted a retrospective, observational study of 578 patients with unresectable HCC treated with ICI from 2017 to 2019 at 13 institutions across three continents. BB use was defined as exposure to BBs at any time during ICI therapy. The primary objective was to assess the association of BB exposure with overall survival (OS). Secondary objectives were to evaluate the association of BB use with progression-free survival (PFS) and objective response rate (ORR) according to RECIST 1.1 criteria.ResultsIn our study cohort, 203 (35%) patients used BBs at any point during ICI therapy. Of these, 51% were taking a nonselective BB. BB use was not significantly correlated with OS (hazard ratio [HR] 1.12, 95% CI 0.9-1.39, P = 0.298), PFS (HR 1.02, 95% CI 0.83-1.26, P = 0.844) or ORR (odds ratio [OR] 0.84, 95% CI 0.54-1.31, P = 0.451) in univariate or multivariate analyses. BB use was also not associated with incidence of adverse events (OR 1.38, 95% CI 0.96-1.97, P = 0.079). Specifically, nonselective BB use was not correlated with OS (HR 0.94, 95% CI 0.66-1.33, P = 0.721), PFS (HR 0.92, 0.66-1.29, P = 0.629), ORR (OR 1.20, 95% CI 0.58-2.49, P = 0.623), or rate of adverse events (OR 0.82, 95% CI 0.46-1.47, P = 0.510).ConclusionIn this real-world population of patients with unresectable HCC treated with immunotherapy, BB use was not associated with OS, PFS or ORR.https://www.frontiersin.org/articles/10.3389/fonc.2023.1128569/fullhepatocellular carcinomaimmune checkpoint inhibitorscancer immunotherapybeta-adrenergic blockadebeta blocker |
| spellingShingle | Y. Linda Wu Grace van Hyfte Umut Özbek Marlene Reincke Anuhya Gampa Yehia I. Mohamed Naoshi Nishida Brooke Wietharn Suneetha Amara Pei-Chang Lee Bernhard Scheiner Lorenz Balcar Matthias Pinter Arndt Vogel Arndt Weinmann Anwaar Saeed Anjana Pillai Lorenza Rimassa Lorenza Rimassa Abdul Rafeh Naqash Mahvish Muzaffar Yi-Hsiang Huang Ahmed O. Kaseb Masatoshi Kudo David J. Pinato Celina Ang Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors Frontiers in Oncology hepatocellular carcinoma immune checkpoint inhibitors cancer immunotherapy beta-adrenergic blockade beta blocker |
| title | Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors |
| title_full | Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors |
| title_fullStr | Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors |
| title_full_unstemmed | Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors |
| title_short | Outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors |
| title_sort | outcomes of beta blocker use in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors |
| topic | hepatocellular carcinoma immune checkpoint inhibitors cancer immunotherapy beta-adrenergic blockade beta blocker |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1128569/full |
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