Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy

The impact of corticosteroid therapy (CT) on efficacy of immune checkpoint inhibitors (ICI) is undefined in hepatocellular carcinoma (HCC). We evaluated whether CT administered at baseline (bCT) or concurrently with ICI (cCT) influences overall (OS), progression-free survival (PFS) and overall respo...

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Main Authors: Dominik Bettinger, Bo Yu, David Szafron, Yinghong Wang, Abdul Rafeh Naqash, Mahvish Muzaffar, Uqba Khan, Yi-Hsiang Huang, David J Pinato, Ahmed Kaseb, Anwaar Saeed, Tomi Jun, Sirish Dharmapuri, Musharraf Navaid, ChiehJu Lee, Anushi Bulumulle, Sonal Paul, Petros Fessas, Neil Nimkar, Hannah Hildebrand, Tiziana Pressiani, Yehia I Abugabal, Nicola Personeni, Jingky Lozano-Kuehne, Lorenza Rimassa, Celina Ang, Thomas U Marron
Format: Article
Language:English
Published: BMJ Publishing Group 2020-10-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/8/2/e000726.full
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author Dominik Bettinger
Bo Yu
David Szafron
Yinghong Wang
Abdul Rafeh Naqash
Mahvish Muzaffar
Uqba Khan
Yi-Hsiang Huang
David J Pinato
Ahmed Kaseb
Anwaar Saeed
Tomi Jun
Sirish Dharmapuri
Musharraf Navaid
ChiehJu Lee
Anushi Bulumulle
Sonal Paul
Petros Fessas
Neil Nimkar
Hannah Hildebrand
Tiziana Pressiani
Yehia I Abugabal
Nicola Personeni
Jingky Lozano-Kuehne
Lorenza Rimassa
Celina Ang
Thomas U Marron
author_facet Dominik Bettinger
Bo Yu
David Szafron
Yinghong Wang
Abdul Rafeh Naqash
Mahvish Muzaffar
Uqba Khan
Yi-Hsiang Huang
David J Pinato
Ahmed Kaseb
Anwaar Saeed
Tomi Jun
Sirish Dharmapuri
Musharraf Navaid
ChiehJu Lee
Anushi Bulumulle
Sonal Paul
Petros Fessas
Neil Nimkar
Hannah Hildebrand
Tiziana Pressiani
Yehia I Abugabal
Nicola Personeni
Jingky Lozano-Kuehne
Lorenza Rimassa
Celina Ang
Thomas U Marron
author_sort Dominik Bettinger
collection DOAJ
description The impact of corticosteroid therapy (CT) on efficacy of immune checkpoint inhibitors (ICI) is undefined in hepatocellular carcinoma (HCC). We evaluated whether CT administered at baseline (bCT) or concurrently with ICI (cCT) influences overall (OS), progression-free survival (PFS) and overall response rates (ORR) in 341 patients collected across 3 continents. Of 304 eligible patients, 78 (26%) received >10 mg prednisone equivalent daily either as bCT (n=14, 5%) or cCT (n=64, 21%). Indications for CT included procedure/prophylaxis (n=37, 47%), management of immune-related adverse event (n=27, 35%), cancer-related symptoms (n=8, 10%) or comorbidities (n=6, 8%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in univariable and multivariable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (p<0.001) and was associated with refractoriness to ICI (75% vs 33%, p=0.05) compared with cancer-unrelated indications. This is the first study to demonstrate that neither bCT nor cCT influence response and OS following ICI in HCC. Worse outcomes in CT recipients for cancer-related indications appear driven by the poor prognosis associated with symptomatic HCC.
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spelling doaj-art-fd5dfa2eba3b4f96a6696a68a05a1a492025-08-20T02:13:19ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-000726Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapyDominik Bettinger0Bo Yu1David Szafron2Yinghong Wang3Abdul Rafeh Naqash4Mahvish Muzaffar5Uqba Khan6Yi-Hsiang Huang7David J Pinato8Ahmed Kaseb9Anwaar Saeed10Tomi Jun11Sirish Dharmapuri12Musharraf Navaid13ChiehJu Lee14Anushi Bulumulle15Sonal Paul16Petros Fessas17Neil Nimkar18Hannah Hildebrand19Tiziana Pressiani20Yehia I Abugabal21Nicola Personeni22Jingky Lozano-Kuehne23Lorenza Rimassa24Celina Ang25Thomas U Marron2611 Department of Medicine II, Faculty of Medicine, Medical Center University of Freiburg, Freiburg, GermanyDepartment of Medicine, New York City Health and Hospitals/ Lincoln, New York City, New York, USA2 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA3 Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USAMedical Oncology/TSET Phase 1 Program, The University of Oklahoma Stephenson Cancer Center, Oklahoma City, Oklahoma, USA7 Division of Hematology/Oncology, East Carolina University, Greenville, North Carolina, United States8 Division of Hematology and Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, Ithaca, New York, USA9 Division of Gastroenterology and Hepatology, Department of Medicine at Taipei Veterans General Hospital and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan16 Department of Surgery & Cancer, Imperial College London, London, UK2 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA4 Division of Medical Oncology, Kansas University Cancer Center, Kansas City, Kansas, USA5 Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital School of Medicine, New York, New York, USA5 Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai Hospital School of Medicine, New York, New York, USA7 Division of Hematology/Oncology, East Carolina University, Greenville, North Carolina, USA9 Division of Gastroenterology and Hepatology, Department of Medicine at Taipei Veterans General Hospital and Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan10 Brody School of Medicine at East Carolina University, Greenville, North Carolina, USA10 Department of Medicine, New York Presbyterian Brooklyn Methodist Hospital, Brooklyn, New York, United States11 Surgery and Cancer, Imperial College London, London, UK8 Division of Hematology and Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, Ithaca, New York, USA4 Division of Medical Oncology, Kansas University Cancer Center, Kansas City, Kansas, USA13 Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano, Milan, Italy2 Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA13 Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano, Milan, ItalyPopulation Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK13 Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, IRCCS, Via Manzoni 56, 20089 Rozzano, Milan, Italy1Icahn School of Medicine at Mount Sinai, New York, NY, USADepartment of Medicine, Division of Hematology Oncology, Mount Sinai School of Medicine, New York, New York, USAThe impact of corticosteroid therapy (CT) on efficacy of immune checkpoint inhibitors (ICI) is undefined in hepatocellular carcinoma (HCC). We evaluated whether CT administered at baseline (bCT) or concurrently with ICI (cCT) influences overall (OS), progression-free survival (PFS) and overall response rates (ORR) in 341 patients collected across 3 continents. Of 304 eligible patients, 78 (26%) received >10 mg prednisone equivalent daily either as bCT (n=14, 5%) or cCT (n=64, 21%). Indications for CT included procedure/prophylaxis (n=37, 47%), management of immune-related adverse event (n=27, 35%), cancer-related symptoms (n=8, 10%) or comorbidities (n=6, 8%). Neither overall CT, bCT nor cCT predicted for worse OS, PFS nor ORR in univariable and multivariable analyses (p>0.05). CT for cancer-related indications predicted for shorter PFS (p<0.001) and was associated with refractoriness to ICI (75% vs 33%, p=0.05) compared with cancer-unrelated indications. This is the first study to demonstrate that neither bCT nor cCT influence response and OS following ICI in HCC. Worse outcomes in CT recipients for cancer-related indications appear driven by the poor prognosis associated with symptomatic HCC.https://jitc.bmj.com/content/8/2/e000726.full
spellingShingle Dominik Bettinger
Bo Yu
David Szafron
Yinghong Wang
Abdul Rafeh Naqash
Mahvish Muzaffar
Uqba Khan
Yi-Hsiang Huang
David J Pinato
Ahmed Kaseb
Anwaar Saeed
Tomi Jun
Sirish Dharmapuri
Musharraf Navaid
ChiehJu Lee
Anushi Bulumulle
Sonal Paul
Petros Fessas
Neil Nimkar
Hannah Hildebrand
Tiziana Pressiani
Yehia I Abugabal
Nicola Personeni
Jingky Lozano-Kuehne
Lorenza Rimassa
Celina Ang
Thomas U Marron
Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy
Journal for ImmunoTherapy of Cancer
title Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy
title_full Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy
title_fullStr Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy
title_full_unstemmed Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy
title_short Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy
title_sort impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy
url https://jitc.bmj.com/content/8/2/e000726.full
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