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Pelizzaro et al. Hepatoma Res 2021;7:36 Hepatoma Research
DOI: 10.20517/2394-5079.2021.24

Commentary Open Access

Systemic therapies for hepatocellular carcinoma: an

evolving landscape

2
1
Filippo Pelizzaro , Giuliano Ramadori , Fabio Farinati 1
1
Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit, University of Padova, Padova 35128, Italy.
2
Department of Gastroenterology and Endocrinology, University Medical Center Goettingen, Goettingen D-37075, Germany.
Correspondence to: Prof. Fabio Farinati, Department of Surgery, Oncology and Gastroenterology, Gastroenterology Unit,
University of Padova, Via Giustiniani 2, Padova 35128, Italy. E-mail: fabio.farinati@unipd.it
How to cite this article: Pelizzaro F, Ramadori G, Farinati F. Systemic therapies for hepatocellular carcinoma: an evolving
landscape. Hepatoma Res 2021;7:36. https://dx.doi.org/10.20517/2394-5079.2021.24

Received: 22 Feb 2021 First Decision: 25 Apr 2021 Revised: 26 Apr 2021 Accepted: 26 Apr 2021 Published: 8 May 2021

Academic Editor: Guang-Wen Cao Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
In the last few years, there has been a significant widening of the landscape of systemic therapy for unresectable
hepatocellular carcinoma (HCC) patients. After the landmark drug sorafenib, several other molecules have been
approved for treatment in first-line (lenvatinib) and second-line (regorafenib, cabozantinib, and ramucirumab)
regimens. Very recently, another important step forward has been made with the demonstration that the
combination of an anti-programmed death ligand 1 and an anti-vascular endothelial growth factor (atezolizumab +
bevacizumab) provides better survival results compared to sorafenib, thus becoming the new paradigm in first-line
treatment of HCC. In consideration of this rapidly evolving situation, with the availability of many potential active
drugs, the American Society of Clinical Oncology recently published a guideline in order to advise on the selection
of systemic treatment options. However, also considering the uncertainties and the unmet needs in the current
treatment of patients with advanced liver cancer is mandatory.

Keywords: Hepatocellular carcinoma, systemic therapies, tyrosine kinase inhibitors, immune checkpoint inhibitors,
atezolizumab, bevacizumab, American Society of Clinical Oncology (ASCO)

The search for effective systemic therapy in hepatocellular carcinoma (HCC) patients has been very intense
for many years, but all the initial drugs investigated (chemotherapy and hormonal compounds) proved to
be ineffective . Among the most promising molecules, tyrosine kinase inhibitors (TKIs) attracted great
[1]
attention due to their ability to block intracellular pathways involved in several biological activities in HCC

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
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