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Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study

Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients curr...

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Autores principales: Kudo, Masatoshi, Ueshima, Kazuomi, Chan, Stephan, Minami, Tomohiro, Chishina, Hirokazu, Aoki, Tomoko, Takita, Masahiro, Hagiwara, Satoru, Minami, Yasunori, Ida, Hiroshi, Takenaka, Mamoru, Sakurai, Toshiharu, Watanabe, Tomohiro, Morita, Masahiro, Ogawa, Chikara, Wada, Yoshiyuki, Ikeda, Masafumi, Ishii, Hiroshi, Izumi, Namiki, Nishida, Naoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721438/
https://www.ncbi.nlm.nih.gov/pubmed/31370183
http://dx.doi.org/10.3390/cancers11081084
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author Kudo, Masatoshi
Ueshima, Kazuomi
Chan, Stephan
Minami, Tomohiro
Chishina, Hirokazu
Aoki, Tomoko
Takita, Masahiro
Hagiwara, Satoru
Minami, Yasunori
Ida, Hiroshi
Takenaka, Mamoru
Sakurai, Toshiharu
Watanabe, Tomohiro
Morita, Masahiro
Ogawa, Chikara
Wada, Yoshiyuki
Ikeda, Masafumi
Ishii, Hiroshi
Izumi, Namiki
Nishida, Naoshi
author_facet Kudo, Masatoshi
Ueshima, Kazuomi
Chan, Stephan
Minami, Tomohiro
Chishina, Hirokazu
Aoki, Tomoko
Takita, Masahiro
Hagiwara, Satoru
Minami, Yasunori
Ida, Hiroshi
Takenaka, Mamoru
Sakurai, Toshiharu
Watanabe, Tomohiro
Morita, Masahiro
Ogawa, Chikara
Wada, Yoshiyuki
Ikeda, Masafumi
Ishii, Hiroshi
Izumi, Namiki
Nishida, Naoshi
author_sort Kudo, Masatoshi
collection PubMed
description Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child–Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were −2.61 to −2.61 for 30 patients in the lenvatinib group (p = 0.254) and −2.66 to −2.09 in the cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child–Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE.
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spelling pubmed-67214382019-09-10 Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study Kudo, Masatoshi Ueshima, Kazuomi Chan, Stephan Minami, Tomohiro Chishina, Hirokazu Aoki, Tomoko Takita, Masahiro Hagiwara, Satoru Minami, Yasunori Ida, Hiroshi Takenaka, Mamoru Sakurai, Toshiharu Watanabe, Tomohiro Morita, Masahiro Ogawa, Chikara Wada, Yoshiyuki Ikeda, Masafumi Ishii, Hiroshi Izumi, Namiki Nishida, Naoshi Cancers (Basel) Article Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child–Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were −2.61 to −2.61 for 30 patients in the lenvatinib group (p = 0.254) and −2.66 to −2.09 in the cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child–Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE. MDPI 2019-07-31 /pmc/articles/PMC6721438/ /pubmed/31370183 http://dx.doi.org/10.3390/cancers11081084 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kudo, Masatoshi
Ueshima, Kazuomi
Chan, Stephan
Minami, Tomohiro
Chishina, Hirokazu
Aoki, Tomoko
Takita, Masahiro
Hagiwara, Satoru
Minami, Yasunori
Ida, Hiroshi
Takenaka, Mamoru
Sakurai, Toshiharu
Watanabe, Tomohiro
Morita, Masahiro
Ogawa, Chikara
Wada, Yoshiyuki
Ikeda, Masafumi
Ishii, Hiroshi
Izumi, Namiki
Nishida, Naoshi
Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study
title Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study
title_full Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study
title_fullStr Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study
title_full_unstemmed Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study
title_short Lenvatinib as an Initial Treatment in Patients with Intermediate-Stage Hepatocellular Carcinoma Beyond Up-To-Seven Criteria and Child–Pugh A Liver Function: A Proof-Of-Concept Study
title_sort lenvatinib as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria and child–pugh a liver function: a proof-of-concept study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721438/
https://www.ncbi.nlm.nih.gov/pubmed/31370183
http://dx.doi.org/10.3390/cancers11081084
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