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Targeted agents for second-line treatment of advanced hepatocellular carcinoma
Over the past ten years, sorafenib, a multikinase inhibitor, has been the standard of care for patients with unresectable hepatocellular carcinoma (HCC) and well-preserved liver function. Recently, lenvatinib, a different multikinase inhibitor, was shown to be non-inferior to sorafenib, in terms of...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Baishideng Publishing Group Inc
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815920/ https://www.ncbi.nlm.nih.gov/pubmed/31662820 http://dx.doi.org/10.4251/wjgo.v11.i10.788 |
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author | Personeni, Nicola Pressiani, Tiziana Bozzarelli, Silvia Rimassa, Lorenza |
author_facet | Personeni, Nicola Pressiani, Tiziana Bozzarelli, Silvia Rimassa, Lorenza |
author_sort | Personeni, Nicola |
collection | PubMed |
description | Over the past ten years, sorafenib, a multikinase inhibitor, has been the standard of care for patients with unresectable hepatocellular carcinoma (HCC) and well-preserved liver function. Recently, lenvatinib, a different multikinase inhibitor, was shown to be non-inferior to sorafenib, in terms of survival, while all other agents previously tested failed to prove non-inferiority (or superiority) when compared to sorafenib. Similarly, in the second-line setting, most investigational drugs failed to provide better survival outcomes than placebo. However, in the last 2 years three positive phase III trials have been published in this setting. The RESORCE trial, a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib, showed better outcomes with regorafenib compared to placebo. More recently, the phase III CELESTIAL trial demonstrated the superiority of cabozantinib, a multikinase inhibitor targeting vascular endothelial growth factor receptor, MET, and AXL, vs placebo in the second- and third-line setting in patients progressing on or intolerant to sorafenib. The survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein levels. Overall, the adverse events reported in these trials were in line with the known safety profiles of the tested agents. After nearly a decade of a certain degree of stagnation, we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC. |
format | Online Article Text |
id | pubmed-6815920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-68159202019-10-29 Targeted agents for second-line treatment of advanced hepatocellular carcinoma Personeni, Nicola Pressiani, Tiziana Bozzarelli, Silvia Rimassa, Lorenza World J Gastrointest Oncol Review Over the past ten years, sorafenib, a multikinase inhibitor, has been the standard of care for patients with unresectable hepatocellular carcinoma (HCC) and well-preserved liver function. Recently, lenvatinib, a different multikinase inhibitor, was shown to be non-inferior to sorafenib, in terms of survival, while all other agents previously tested failed to prove non-inferiority (or superiority) when compared to sorafenib. Similarly, in the second-line setting, most investigational drugs failed to provide better survival outcomes than placebo. However, in the last 2 years three positive phase III trials have been published in this setting. The RESORCE trial, a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib, showed better outcomes with regorafenib compared to placebo. More recently, the phase III CELESTIAL trial demonstrated the superiority of cabozantinib, a multikinase inhibitor targeting vascular endothelial growth factor receptor, MET, and AXL, vs placebo in the second- and third-line setting in patients progressing on or intolerant to sorafenib. The survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein levels. Overall, the adverse events reported in these trials were in line with the known safety profiles of the tested agents. After nearly a decade of a certain degree of stagnation, we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC. Baishideng Publishing Group Inc 2019-10-15 2019-10-15 /pmc/articles/PMC6815920/ /pubmed/31662820 http://dx.doi.org/10.4251/wjgo.v11.i10.788 Text en ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Review Personeni, Nicola Pressiani, Tiziana Bozzarelli, Silvia Rimassa, Lorenza Targeted agents for second-line treatment of advanced hepatocellular carcinoma |
title | Targeted agents for second-line treatment of advanced hepatocellular carcinoma |
title_full | Targeted agents for second-line treatment of advanced hepatocellular carcinoma |
title_fullStr | Targeted agents for second-line treatment of advanced hepatocellular carcinoma |
title_full_unstemmed | Targeted agents for second-line treatment of advanced hepatocellular carcinoma |
title_short | Targeted agents for second-line treatment of advanced hepatocellular carcinoma |
title_sort | targeted agents for second-line treatment of advanced hepatocellular carcinoma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6815920/ https://www.ncbi.nlm.nih.gov/pubmed/31662820 http://dx.doi.org/10.4251/wjgo.v11.i10.788 |
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