Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort

Bernhard Scheiner; Martha M. Kirstein; Florian Hucke; Fabian Finkelmeier; Kornelius Schulze; Johann von Felden; Sandra Koch; Philipp Schwabl; Jan B. Hinrichs; Fredrik Waneck; Oliver Waidmann; Thomas Reiberger; Christian Müller; Wolfgang Sieghart; Michael Trauner; Arndt Weinmann; Henning Wege; Jörg Trojan; Markus Peck-Radosavljevic; Arndt Vogel; Matthias Pinter

doi:10.1111/apt.15245

Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort

Bernhard Scheiner, Martha M. Kirstein, Florian Hucke, Fabian Finkelmeier, Kornelius Schulze, Johann von Felden, Sandra Koch, Philipp Schwabl, Jan B. Hinrichs, Fredrik Waneck, Oliver Waidmann, Thomas Reiberger, Christian Müller, Wolfgang Sieghart, Michael Trauner, Arndt Weinmann, Henning Wege, Jörg Trojan, Markus Peck-Radosavljevic, Arndt VogelMatthias Pinter^*

^*Korrespondierende/r Autor/-in für diese Arbeit

Medizinische Klinik I

111 Zitate (Scopus)

Abstract

Background: Programmed cell death protein-1-targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma. Aim: To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real-world cohort of patients with advanced hepatocellular carcinoma. Methods: Sixty-five patients treated with nivolumab (n = 34) or pembrolizumab (n = 31) between July 10, 2015 and December 31, 2018 (data cut-off) across six centres in Austria and Germany were retrospectively analysed. Results: Child-Pugh class A/B/C was 32 (49%)/28 (43%)/5 (8%). Immunotherapy was used as systemic first-/second-/third-/fourth-line treatment in 9 (14%)/27 (42%)/26 (40%)/3 (5%) patients. Fifty-four patients had at least one follow-up imaging and were, therefore, available for radiological response assessment. The overall response and disease control rates were 12% and 49% respectively. Of 52 evaluable patients, four (8%) had hyperprogressive disease. Median time to progression was 5.5 (95% CI, 3.5-7.4) months, median progression-free survival was 4.6 (95% CI, 3.0-6.2) months, and median overall survival was 11.0 (95% CI, 8.2-13.8) months. Most common adverse events were infections (n = 7), rash (n = 6), pruritus (n = 3), fatigue (n = 3), diarrhoea (n = 3) and hepatitis (n = 3). Efficacy and safety results were comparable between Child-Pugh A and B patients; however, median overall survival (OS) was shorter in Child-Pugh B patients (16.7 vs 8.6 months; P = 0.065). There was no difference in terms of efficacy and adverse events between patients who received immunotherapy as first-/second-line and third-/fourth-line respectively. Conclusions: Programmed cell death protein-1-targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patients with advanced hepatocellular carcinoma, including subjects with Child-Pugh stage B and patients with intensive pretreatment.

Originalsprache	Englisch
Zeitschrift	Alimentary Pharmacology and Therapeutics
Jahrgang	49
Ausgabenummer	10
Seiten (von - bis)	1323-1333
Seitenumfang	11
ISSN	0269-2813
DOIs	https://doi.org/10.1111/apt.15245
Publikationsstatus	Veröffentlicht - 05.2019

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Roche, Lilly, Janssen, MSD, and BMS. S.K. has nothing to disclose. P.S. served as a speaker for Boehringer Ingelheim and Bristol‐ Myers Squibb. J.B.H. has nothing to disclose. O.W. served as con‐ sultant for Amgen, Bayer, BMS, Celgene, Eisai, Merck, Novartis, Roche, Servier, and Shire. He served as a speaker for Abbvie, Bayer, BMS, Celgene, Falk, Ipsen, Novartis, Roche, and Shire and received travel support from Abbvie, BMS, Ipsen, Novartis, and Servier. T.R. served as a speaker and/or consultant and/or advisory board member for AbbVie, Bayer, Boehringer Ingelheim, Gilead, W. L. Gore & Associates, and MSD and has received research funding from AbbVie, Boehringer Ingelheim, Gilead, MSD, Phenex Pharmaceuticals, and Philips. C.M. received travel support from Bayer. W.S. received speaker and consulting fees and research grants from Bayer Schering Pharma and served as consultant for Eisai, Lilly, MSD, and BMS. M.T. served as speaker for BMS, Falk, Gilead, and MSD; advisory boards for Albireo, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex, and Regulus. He further re‐ ceived travel grants from Abbvie, Falk, Gilead, and Intercept, and unrestricted research grants from Albireo, Cymabay, Falk, Gilead, Intercept, MSD, and Takeda. He is also the co‐inventor of a patent on the medical use of norUDCA. A.W. is advisor for BMS, Wako, Eisai, Roche, and Amgen. H.W. served as speaker for Bayer, Eisai and Ipsen, and as a consultant for Bayer, Eisai, Lilly, BMS, Roche and Ipsen. He conducts studies for Bayer, Roche, Lilly, MSD and BMS. J.T. served as consultant for Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen and Roche, and received travel support from BMS and Ipsen, and speaking fees from Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen and Roche. He is also an in‐ vestigator for Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen and Roche. M.P.‐R. is advisor/consultant for Astra Zeneca, Bayer, BMS, Eisai, Ipsen, Lilly and MSD; he served as a speaker for Bayer, Eisai, and Lilly and is an investigator for Bayer, BMS, Exelixis and Lilly. A.V. served as consultant for Roche, Bayer, Lilly, BMS, Eisai, and Ipsen and received speaking fees from Roche, Bayer, Lilly, BMS, Eisai and Ipsen. He is also an investigator for Roche, Bayer, Lilly, BMS, Eisai and Ipsen. M.P. served as consultant for Bayer, BMS, Eisai, Ipsen and Lilly, and received travel support from Bayer and speaking fees from Bayer, BMS and MSD. He is also an investigator for Bayer, BMS and Lilly. We thank David Bauer (Division of Gastroenterology & Hepatology, Medical University of Vienna) for helping with evaluation of hyperprogressive disease. Declaration of personal interests: B.S. received travel support from AbbVie and Gilead. M.K. received honoraria from BMS as consultant and is an investigator for AstraZeneca and BMS. F.H. received travel support from Bayer, Abbvie, and Gilead. F.F. received travel support from Abbvie and Novartis. K.S. served as consultant for Ipsen and Bayer, and conducts studies for Bayer, Roche, Lilly, MSD, and BMS. J.v.F. is an investigator for Bayer, Roche, Lilly, Janssen, MSD, and BMS. S.K. has nothing to disclose. P.S. served as a speaker for Boehringer Ingelheim and Bristol-Myers Squibb. J.B.H. has nothing to disclose. O.W. served as consultant for Amgen, Bayer, BMS, Celgene, Eisai, Merck, Novartis, Roche, Servier, and Shire. He served as a speaker for Abbvie, Bayer, BMS, Celgene, Falk, Ipsen, Novartis, Roche, and Shire and received travel support from Abbvie, BMS, Ipsen, Novartis, and Servier. T.R. served as a speaker and/or consultant and/or advisory board member for AbbVie, Bayer, Boehringer Ingelheim, Gilead, W. L. Gore & Associates, and MSD and has received research funding from AbbVie, Boehringer Ingelheim, Gilead, MSD, Phenex Pharmaceuticals, and Philips. C.M. received travel support from Bayer. W.S. received speaker and consulting fees and research grants from Bayer Schering Pharma and served as consultant for Eisai, Lilly, MSD, and BMS. M.T. served as speaker for BMS, Falk, Gilead, and MSD; advisory boards for Albireo, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex, and Regulus. He further received travel grants from Abbvie, Falk, Gilead, and Intercept, and unrestricted research grants from Albireo, Cymabay, Falk, Gilead, Intercept, MSD, and Takeda. He is also the co-inventor of a patent on the medical use of norUDCA. A.W. is advisor for BMS, Wako, Eisai, Roche, and Amgen. H.W. served as speaker for Bayer, Eisai and Ipsen, and as a consultant for Bayer, Eisai, Lilly, BMS, Roche and Ipsen. He conducts studies for Bayer, Roche, Lilly, MSD and BMS. J.T. served as consultant for Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen and Roche, and received travel support from BMS and Ipsen, and speaking fees from Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen and Roche. He is also an investigator for Amgen, Bayer, BMS, Eisai, Lilly, Merck Serono, MSD, Ipsen and Roche. M.P.-R. is advisor/consultant for Astra Zeneca, Bayer, BMS, Eisai, Ipsen, Lilly and MSD; he served as a speaker for Bayer, Eisai, and Lilly and is an investigator for Bayer, BMS, Exelixis and Lilly. A.V. served as consultant for Roche, Bayer, Lilly, BMS, Eisai, and Ipsen and received speaking fees from Roche, Bayer, Lilly, BMS, Eisai and Ipsen. He is also an investigator for Roche, Bayer, Lilly, BMS, Eisai and Ipsen. M.P. served as consultant for Bayer, BMS, Eisai, Ipsen and Lilly, and received travel support from Bayer and speaking fees from Bayer, BMS and MSD. He is also an investigator for Bayer, BMS and Lilly.

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Scheiner, B., Kirstein, M. M., Hucke, F., Finkelmeier, F., Schulze, K., von Felden, J., Koch, S., Schwabl, P., Hinrichs, J. B., Waneck, F., Waidmann, O., Reiberger, T., Müller, C., Sieghart, W., Trauner, M., Weinmann, A., Wege, H., Trojan, J., Peck-Radosavljevic, M., ... Pinter, M. (2019). Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort. Alimentary Pharmacology and Therapeutics, 49(10), 1323-1333. https://doi.org/10.1111/apt.15245

@article{991a0252bf064593980d90a73fe40fef,

title = "Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort",

abstract = "Background: Programmed cell death protein-1-targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma. Aim: To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real-world cohort of patients with advanced hepatocellular carcinoma. Methods: Sixty-five patients treated with nivolumab (n = 34) or pembrolizumab (n = 31) between July 10, 2015 and December 31, 2018 (data cut-off) across six centres in Austria and Germany were retrospectively analysed. Results: Child-Pugh class A/B/C was 32 (49\%)/28 (43\%)/5 (8\%). Immunotherapy was used as systemic first-/second-/third-/fourth-line treatment in 9 (14\%)/27 (42\%)/26 (40\%)/3 (5\%) patients. Fifty-four patients had at least one follow-up imaging and were, therefore, available for radiological response assessment. The overall response and disease control rates were 12\% and 49\% respectively. Of 52 evaluable patients, four (8\%) had hyperprogressive disease. Median time to progression was 5.5 (95\% CI, 3.5-7.4) months, median progression-free survival was 4.6 (95\% CI, 3.0-6.2) months, and median overall survival was 11.0 (95\% CI, 8.2-13.8) months. Most common adverse events were infections (n = 7), rash (n = 6), pruritus (n = 3), fatigue (n = 3), diarrhoea (n = 3) and hepatitis (n = 3). Efficacy and safety results were comparable between Child-Pugh A and B patients; however, median overall survival (OS) was shorter in Child-Pugh B patients (16.7 vs 8.6 months; P = 0.065). There was no difference in terms of efficacy and adverse events between patients who received immunotherapy as first-/second-line and third-/fourth-line respectively. Conclusions: Programmed cell death protein-1-targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patients with advanced hepatocellular carcinoma, including subjects with Child-Pugh stage B and patients with intensive pretreatment.",

author = "Bernhard Scheiner and Kirstein, \{Martha M.\} and Florian Hucke and Fabian Finkelmeier and Kornelius Schulze and \{von Felden\}, Johann and Sandra Koch and Philipp Schwabl and Hinrichs, \{Jan B.\} and Fredrik Waneck and Oliver Waidmann and Thomas Reiberger and Christian M{\"u}ller and Wolfgang Sieghart and Michael Trauner and Arndt Weinmann and Henning Wege and J{\"o}rg Trojan and Markus Peck-Radosavljevic and Arndt Vogel and Matthias Pinter",

note = "Publisher Copyright: {\textcopyright} 2019 The Authors. Alimentary Pharmacology \& Therapeutics Published by John Wiley \& Sons Ltd.",

year = "2019",

month = may,

doi = "10.1111/apt.15245",

language = "English",

volume = "49",

pages = "1323--1333",

journal = "Alimentary Pharmacology and Therapeutics",

issn = "0269-2813",

publisher = "John Wiley and Sons Inc",

number = "10",

}

Scheiner, B, Kirstein, MM, Hucke, F, Finkelmeier, F, Schulze, K, von Felden, J, Koch, S, Schwabl, P, Hinrichs, JB, Waneck, F, Waidmann, O, Reiberger, T, Müller, C, Sieghart, W, Trauner, M, Weinmann, A, Wege, H, Trojan, J, Peck-Radosavljevic, M, Vogel, A & Pinter, M 2019, 'Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort', Alimentary Pharmacology and Therapeutics, Jg. 49, Nr. 10, S. 1323-1333. https://doi.org/10.1111/apt.15245

Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort. / Scheiner, Bernhard; Kirstein, Martha M.; Hucke, Florian et al.
in: Alimentary Pharmacology and Therapeutics, Jahrgang 49, Nr. 10, 05.2019, S. 1323-1333.

Publikation: Beiträge in Fachzeitschriften › Zeitschriftenaufsätze › Forschung › Begutachtung

TY - JOUR

T1 - Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort

AU - Scheiner, Bernhard

AU - Kirstein, Martha M.

AU - Hucke, Florian

AU - Finkelmeier, Fabian

AU - Schulze, Kornelius

AU - von Felden, Johann

AU - Koch, Sandra

AU - Schwabl, Philipp

AU - Hinrichs, Jan B.

AU - Waneck, Fredrik

AU - Waidmann, Oliver

AU - Reiberger, Thomas

AU - Müller, Christian

AU - Sieghart, Wolfgang

AU - Trauner, Michael

AU - Weinmann, Arndt

AU - Wege, Henning

AU - Trojan, Jörg

AU - Peck-Radosavljevic, Markus

AU - Vogel, Arndt

AU - Pinter, Matthias

PY - 2019/5

Y1 - 2019/5

N2 - Background: Programmed cell death protein-1-targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma. Aim: To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real-world cohort of patients with advanced hepatocellular carcinoma. Methods: Sixty-five patients treated with nivolumab (n = 34) or pembrolizumab (n = 31) between July 10, 2015 and December 31, 2018 (data cut-off) across six centres in Austria and Germany were retrospectively analysed. Results: Child-Pugh class A/B/C was 32 (49%)/28 (43%)/5 (8%). Immunotherapy was used as systemic first-/second-/third-/fourth-line treatment in 9 (14%)/27 (42%)/26 (40%)/3 (5%) patients. Fifty-four patients had at least one follow-up imaging and were, therefore, available for radiological response assessment. The overall response and disease control rates were 12% and 49% respectively. Of 52 evaluable patients, four (8%) had hyperprogressive disease. Median time to progression was 5.5 (95% CI, 3.5-7.4) months, median progression-free survival was 4.6 (95% CI, 3.0-6.2) months, and median overall survival was 11.0 (95% CI, 8.2-13.8) months. Most common adverse events were infections (n = 7), rash (n = 6), pruritus (n = 3), fatigue (n = 3), diarrhoea (n = 3) and hepatitis (n = 3). Efficacy and safety results were comparable between Child-Pugh A and B patients; however, median overall survival (OS) was shorter in Child-Pugh B patients (16.7 vs 8.6 months; P = 0.065). There was no difference in terms of efficacy and adverse events between patients who received immunotherapy as first-/second-line and third-/fourth-line respectively. Conclusions: Programmed cell death protein-1-targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patients with advanced hepatocellular carcinoma, including subjects with Child-Pugh stage B and patients with intensive pretreatment.

AB - Background: Programmed cell death protein-1-targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma. Aim: To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real-world cohort of patients with advanced hepatocellular carcinoma. Methods: Sixty-five patients treated with nivolumab (n = 34) or pembrolizumab (n = 31) between July 10, 2015 and December 31, 2018 (data cut-off) across six centres in Austria and Germany were retrospectively analysed. Results: Child-Pugh class A/B/C was 32 (49%)/28 (43%)/5 (8%). Immunotherapy was used as systemic first-/second-/third-/fourth-line treatment in 9 (14%)/27 (42%)/26 (40%)/3 (5%) patients. Fifty-four patients had at least one follow-up imaging and were, therefore, available for radiological response assessment. The overall response and disease control rates were 12% and 49% respectively. Of 52 evaluable patients, four (8%) had hyperprogressive disease. Median time to progression was 5.5 (95% CI, 3.5-7.4) months, median progression-free survival was 4.6 (95% CI, 3.0-6.2) months, and median overall survival was 11.0 (95% CI, 8.2-13.8) months. Most common adverse events were infections (n = 7), rash (n = 6), pruritus (n = 3), fatigue (n = 3), diarrhoea (n = 3) and hepatitis (n = 3). Efficacy and safety results were comparable between Child-Pugh A and B patients; however, median overall survival (OS) was shorter in Child-Pugh B patients (16.7 vs 8.6 months; P = 0.065). There was no difference in terms of efficacy and adverse events between patients who received immunotherapy as first-/second-line and third-/fourth-line respectively. Conclusions: Programmed cell death protein-1-targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patients with advanced hepatocellular carcinoma, including subjects with Child-Pugh stage B and patients with intensive pretreatment.

UR - https://www.scopus.com/pages/publications/85064495617

U2 - 10.1111/apt.15245

DO - 10.1111/apt.15245

M3 - Journal articles

C2 - 30980420

AN - SCOPUS:85064495617

SN - 0269-2813

VL - 49

SP - 1323

EP - 1333

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

IS - 10

ER -

Programmed cell death protein-1 (PD-1)-targeted immunotherapy in advanced hepatocellular carcinoma: efficacy and safety data from an international multicentre real-world cohort

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