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Carr. Hepatoma Res 2019;5:3 Hepatoma Research
DOI: 10.20517/2394-5079.2018.113

Review Open Access

Review of therapies for intermediate and advanced
stage hepatocellular carcinoma, not suitable for
curative therapies: a rapidly changing landscape

Brian I. Carr

Liver Transplantation Institute, Inonu University, Malatya, Turkey and Izmir Biomedicine and Genome Center, Dokuz Eylul University,
Izmir 35340, Turkey.

Correspondence to: Prof. Brian I. Carr, MD, FRCP, PhD, Liver Transplantation Institute, Inonu University, Malatya, Turkey and Izmir
Biomedicine and Genome Center, Dokuz Eylul University, Izmir 35340, Turkey. E-mail: brianicarr@hotmail.com

How to cite this article: Carr BI. Review of therapies for intermediate and advanced stage hepatocellular carcinoma, not suitable for
curative therapies: a rapidly changing landscape. Hepatoma Res 2019;5:3. http://dx.doi.org/10.20517/2394-5079.2018.113
Received: 4 Dec 2018 First Decision: 24 Dec 2018 Revised: 31 Dec 2018 Accepted: 3 Jan 2019 Published: 24 Jan 2019

Science Editor: Guang-Wen Cao Copy Editor: Cui Yu Production Editor: Huan-Liang Wu

Abstract
Recent clinical trials and new agents have permitted greater clarity in the choice of effective agents for that
majority of patients with hepatocellular carcinoma who have advanced disease at diagnosis and thus cannot be
offered potentially curative resection, ablation or liver transplantation. The main treatment for these patients
remains chemoembolization, although evidence for selective internal radiation therapy (SIRT) with SIR-Spheres or
Theraphere, is beginning to suggest that the results with this may be comparable with less toxicity. Patients who
have failed chemoembolization or SIRT or have metastatic disease at presentation are suitable for the multikinase
inhibitor sorafenib (nexavar) or newly-approved lenvatinib (lenvima) as first line therapies. The choice between
which of them to use first is not currently clear. Patients who have failed sorafenib can be offered a choice of FDA-
approved regorafenib (stivarga) or immune checkpoint inhibitor nivolumab (opdivo) as second line agents. For that
considerable percent of patients presenting with macroscopic portal vein thrombosis, the choice appears to be
between multikinase inhibitor or SIRT, given the potential toxicity of chemoembolization in this setting. However,
considering the potency of both nivolumab and regorafenib and the pipeline of new agents such as atezolizumab
(tecentriq) in current clinical trials, including new immune checkpoint inhibitors, this landscape may change within
a couple of years, especially if new evidence arises for the superior effectiveness of combinations of any of these
agents over single agents.

Keywords: Hepatocellular carcinoma, advanced, kinase inhibitors, immune checkpoint inhibitors, transarterial
chemoembolization, selective internal radiation therapy

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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