Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

Massimo Iavarone; Federica Invernizzi; Carolin Czauderna; Marco Sanduzzi-Zamparelli; Sherrie Bhoori; Giuliana Amaddeo; Matteo A. Manini; Miguel F. López; Margarita Anders; Matthias Pinter; Maria J.B. Rodríguez; Mario R. Cristóbal; Gabriel A. Soteras; Federico Piñero; Gerda E. Villadsen; Arndt Weinmann; Gonzalo Crespo; Vincenzo Mazzaferro; Helene Regnault; Massimo De Giorgio; Maria L. González-Diéguez; Maria F. Donato; Maria Varela; Marcus Alexander Wörns; Jordi Bruix; Pietro Lampertico; Maria Reig

doi:10.1111/ajt.15551

Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

Massimo Iavarone^*, Federica Invernizzi, Carolin Czauderna, Marco Sanduzzi-Zamparelli, Sherrie Bhoori, Giuliana Amaddeo, Matteo A. Manini, Miguel F. López, Margarita Anders, Matthias Pinter, Maria J.B. Rodríguez, Mario R. Cristóbal, Gabriel A. Soteras, Federico Piñero, Gerda E. Villadsen, Arndt Weinmann, Gonzalo Crespo, Vincenzo Mazzaferro, Helene Regnault, Massimo De GiorgioMaria L. González-Diéguez, Maria F. Donato, Maria Varela, Marcus Alexander Wörns, Jordi Bruix, Pietro Lampertico, Maria Reig

^*Corresponding author for this work

Clinic of Internal Medicine I

92 Citations (Scopus)

Abstract

Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second-line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib-treated LT patients (2015-2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty-eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1-18.5) years; median time on sorafenib was 11.3 (0.7-76.4) months and 14 (1-591) days from sorafenib discontinuation to regorafenib. During regorafenib (6.3 months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n = 7) and dermatological reaction (n = 5). While no liver rejection was observed, plasma levels of immunosuppressive drugs increased in five. Twenty-four patients developed progression (38% extrahepatic growth, 33% new extrahepatic lesions/vascular invasion). Median OS from regorafenib initiation was 12.9 (95% CI, 6.7-19.1) and 38.4 months (95% CI, 18.5-58.4) for the sorafenib initiation. This is the first study showing safety of regorafenib after LT, thus providing the rational of considering regorafenib in the clinical decision-making in sorafenib-tolerant patients with HCC recurrence after LT.

Original language	English
Journal	American Journal of Transplantation
Volume	19
Issue number	11
Pages (from-to)	3176-3184
Number of pages	9
ISSN	1600-6135
DOIs	https://doi.org/10.1111/ajt.15551
Publication status	Published - 01.11.2019

Funding

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation . M. Iavarone received speaker honoraria from Bayer, Gilead Science, Janssen, BTG, Abbvie, MSD, and is a consultant for BTG; S. Bhoori received speaker honoraria and is a consultant of Bayer, Biocompatibles; M. Sanduzzi Zamparelli received lecture fees from Bayer; F. Piñero received speaker honoraria of Bayer; M. Pinter received speaker honoraria from Bayer and BMS, he is a consultant for Bayer, BMS, Ipsen, Eisai, and Lilly and he received travel support from Bayer; A. Weinmann received lecture fees from Bayer, Leo Pharma and he is consultant for Bayer, Bristol‐Myers Squib, Wako; H. Regnault is consultant for BTG; V. Mazzaferro received speaker honoraria and is a consultant of Terumo, Ipsen AB; M.L. González‐Diéguez received speaking honoraria from Abbvie, Novartis, Gilead and she is a consultant for Gilead; M. Varela received speaker fees from Bayer and she is consultant for Bristol‐Myers‐Squibb, Sirtex, BTG, IPSEN and Bayer; M. A. Wörns received lecture fees from Abbvie, Bayer, Bristol‐Myers Squibb, Celgene, Gilead, Incyte, Ipsen, MSD, Norgine, and is a consultant for Abbvie, Bayer, Bristol‐Myers Squibb, Eisai, Gilead, Ipsen, Norgine, Roche; J. Bruix is a consultant of Arqule, Bayer‐Shering Pharma, Novartis, BMS, BTG‐Biocompatibles, Eisai, Kowa, Terumo, Gilead, Bio‐Alliance, Roche, AbbVie, Merck, Sirtex, Ipsen, Astra‐Medimmune, Incyte, Quirem, Adaptimmune, Lilly, he received speaker honoraria from Bayer‐Shering Pharma, BTG, Eisai, Terumo, Sirtex, Ipsen, he has research and educational grants from Bayer, BTG and received paid conferences from Bayer, BTG and Ipsen; P. Lampertico received speaker honoraria and is a consultant of BMS, Roche, Gilead Sciences, GSK, MSD, Abbvie and Janssen; M. Reig received speaker honoraria of Gilead, BMS, BTG, Lilly and Bayer and she is a consultant of Bayer, BMS, Lilly, AstraZeneca, Ipsen and Roche and have grants from Bayer and Ipsen. M. Reig: received grant support from Instituto de Salud Carlos III (PI15/00145 and PI18/0358). J. Bruix received grant support from Instituto de Salud Carlos III (PI14/00962), Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (grant 2017_SGR_1753), and from the Spanish Health Ministry (Plan Estratégico Nacional contra la Hepatitis C) and also supported by CERCA Programme/Generalitat de Catalunya.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1111/ajt.15551

Cite this

Iavarone, M., Invernizzi, F., Czauderna, C., Sanduzzi-Zamparelli, M., Bhoori, S., Amaddeo, G., Manini, M. A., López, M. F., Anders, M., Pinter, M., Rodríguez, M. J. B., Cristóbal, M. R., Soteras, G. A., Piñero, F., Villadsen, G. E., Weinmann, A., Crespo, G., Mazzaferro, V., Regnault, H., ... Reig, M. (2019). Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation. American Journal of Transplantation, 19(11), 3176-3184. https://doi.org/10.1111/ajt.15551

@article{781353c1033844189fa968c7551a52c0,

title = "Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation",

abstract = "Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second-line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib-treated LT patients (2015-2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty-eight LT patients (57 years, 7\% cirrhotics, 54\% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1-18.5) years; median time on sorafenib was 11.3 (0.7-76.4) months and 14 (1-591) days from sorafenib discontinuation to regorafenib. During regorafenib (6.3 months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n = 7) and dermatological reaction (n = 5). While no liver rejection was observed, plasma levels of immunosuppressive drugs increased in five. Twenty-four patients developed progression (38\% extrahepatic growth, 33\% new extrahepatic lesions/vascular invasion). Median OS from regorafenib initiation was 12.9 (95\% CI, 6.7-19.1) and 38.4 months (95\% CI, 18.5-58.4) for the sorafenib initiation. This is the first study showing safety of regorafenib after LT, thus providing the rational of considering regorafenib in the clinical decision-making in sorafenib-tolerant patients with HCC recurrence after LT.",

author = "Massimo Iavarone and Federica Invernizzi and Carolin Czauderna and Marco Sanduzzi-Zamparelli and Sherrie Bhoori and Giuliana Amaddeo and Manini, \{Matteo A.\} and L{\'o}pez, \{Miguel F.\} and Margarita Anders and Matthias Pinter and Rodr{\'i}guez, \{Maria J.B.\} and Crist{\'o}bal, \{Mario R.\} and Soteras, \{Gabriel A.\} and Federico Pi{\~n}ero and Villadsen, \{Gerda E.\} and Arndt Weinmann and Gonzalo Crespo and Vincenzo Mazzaferro and Helene Regnault and Giorgio, \{Massimo De\} and Gonz{\'a}lez-Di{\'e}guez, \{Maria L.\} and Donato, \{Maria F.\} and Maria Varela and W{\"o}rns, \{Marcus Alexander\} and Jordi Bruix and Pietro Lampertico and Maria Reig",

note = "Publisher Copyright: {\textcopyright} 2019 The American Society of Transplantation and the American Society of Transplant Surgeons",

year = "2019",

month = nov,

day = "1",

doi = "10.1111/ajt.15551",

language = "English",

volume = "19",

pages = "3176--3184",

journal = "American Journal of Transplantation",

issn = "1600-6135",

publisher = "Elsevier B.V.",

number = "11",

}

Iavarone, M, Invernizzi, F, Czauderna, C, Sanduzzi-Zamparelli, M, Bhoori, S, Amaddeo, G, Manini, MA, López, MF, Anders, M, Pinter, M, Rodríguez, MJB, Cristóbal, MR, Soteras, GA, Piñero, F, Villadsen, GE, Weinmann, A, Crespo, G, Mazzaferro, V, Regnault, H, Giorgio, MD, González-Diéguez, ML, Donato, MF, Varela, M, Wörns, MA, Bruix, J, Lampertico, P & Reig, M 2019, 'Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation', American Journal of Transplantation, vol. 19, no. 11, pp. 3176-3184. https://doi.org/10.1111/ajt.15551

Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation. / Iavarone, Massimo; Invernizzi, Federica; Czauderna, Carolin et al.
In: American Journal of Transplantation, Vol. 19, No. 11, 01.11.2019, p. 3176-3184.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

AU - Iavarone, Massimo

AU - Invernizzi, Federica

AU - Czauderna, Carolin

AU - Sanduzzi-Zamparelli, Marco

AU - Bhoori, Sherrie

AU - Amaddeo, Giuliana

AU - Manini, Matteo A.

AU - López, Miguel F.

AU - Anders, Margarita

AU - Pinter, Matthias

AU - Rodríguez, Maria J.B.

AU - Cristóbal, Mario R.

AU - Soteras, Gabriel A.

AU - Piñero, Federico

AU - Villadsen, Gerda E.

AU - Weinmann, Arndt

AU - Crespo, Gonzalo

AU - Mazzaferro, Vincenzo

AU - Regnault, Helene

AU - Giorgio, Massimo De

AU - González-Diéguez, Maria L.

AU - Donato, Maria F.

AU - Varela, Maria

AU - Wörns, Marcus Alexander

AU - Bruix, Jordi

AU - Lampertico, Pietro

AU - Reig, Maria

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second-line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib-treated LT patients (2015-2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty-eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1-18.5) years; median time on sorafenib was 11.3 (0.7-76.4) months and 14 (1-591) days from sorafenib discontinuation to regorafenib. During regorafenib (6.3 months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n = 7) and dermatological reaction (n = 5). While no liver rejection was observed, plasma levels of immunosuppressive drugs increased in five. Twenty-four patients developed progression (38% extrahepatic growth, 33% new extrahepatic lesions/vascular invasion). Median OS from regorafenib initiation was 12.9 (95% CI, 6.7-19.1) and 38.4 months (95% CI, 18.5-58.4) for the sorafenib initiation. This is the first study showing safety of regorafenib after LT, thus providing the rational of considering regorafenib in the clinical decision-making in sorafenib-tolerant patients with HCC recurrence after LT.

AB - Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate the safety and outcomes of regorafenib as second-line treatment for HCC recurrence after liver transplantation (LT). This is a retrospective, multicenter, international study including regorafenib-treated LT patients (2015-2018), with analysis of baseline characteristics and evolutionary events during sorafenib/regorafenib treatment. Twenty-eight LT patients (57 years, 7% cirrhotics, 54% performance status 1) were included. Median time from LT to regorafenib initiation was 3.9 (1.1-18.5) years; median time on sorafenib was 11.3 (0.7-76.4) months and 14 (1-591) days from sorafenib discontinuation to regorafenib. During regorafenib (6.3 months), all patients had at least one adverse event (AE), the most common grade 3/4 AEs were fatigue (n = 7) and dermatological reaction (n = 5). While no liver rejection was observed, plasma levels of immunosuppressive drugs increased in five. Twenty-four patients developed progression (38% extrahepatic growth, 33% new extrahepatic lesions/vascular invasion). Median OS from regorafenib initiation was 12.9 (95% CI, 6.7-19.1) and 38.4 months (95% CI, 18.5-58.4) for the sorafenib initiation. This is the first study showing safety of regorafenib after LT, thus providing the rational of considering regorafenib in the clinical decision-making in sorafenib-tolerant patients with HCC recurrence after LT.

UR - https://www.scopus.com/pages/publications/85071745261

U2 - 10.1111/ajt.15551

DO - 10.1111/ajt.15551

M3 - Journal articles

C2 - 31365177

AN - SCOPUS:85071745261

SN - 1600-6135

VL - 19

SP - 3176

EP - 3184

JO - American Journal of Transplantation

JF - American Journal of Transplantation

IS - 11

ER -

Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation

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