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World J Gastroenterol. Apr 28, 2020; 26(16): 1888-1900
Published online Apr 28, 2020. doi: 10.3748/wjg.v26.i16.1888
Sequencing of systemic treatment for hepatocellular carcinoma: Second line competitors
Federico Piñero, Marcelo Silva, Massimo Iavarone
Federico Piñero, Marcelo Silva, Hospital Universitario Austral, Facultad de Ciencias Biomédicas, Universidad Austral, Buenos Aires B1629HJ, Argentina
Federico Piñero, Marcelo Silva, Latin American Liver Research Educational and Awareness Network, Buenos Aires B1629HJ, Argentina
Massimo Iavarone, Division of Gastroenterology and Hepatology, CRC “A.M. e A. Migliavacca” Center for the Study of Liver Disease, University of Milan, Fondazione IRCCS Ca’ Granda Maggiore Hospital, Milan 20121, Italy
Author contributions: All authors equally contributed to this paper with conception and design of the study, literature review, drafting, critical revision and editing. They all have approved the final version.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Federico Piñero, MD, MSc, Academic Research, Doctor, Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Av. Presidente Perón 1500, Pilar, Buenos Aires B1629HJ, Argentina. fpinerof@cas.austral.edu.ar
Received: December 28, 2019
Peer-review started: December 28, 2019
First decision: January 11, 2020
Revised: March 27, 2020
Accepted: April 4, 2020
Article in press: April 4, 2020
Published online: April 28, 2020
Abstract

During the last decades, further knowledge of hepatocellular carcinoma (HCC) molecular mechanisms has led to development of effective systemic treatments including tyrosine kinase inhibitors (TKIs) and immunotherapy. In this review, we describe first and second line systemic treatment options for advanced HCC. Several trials have evaluated new drugs for the treatment of HCC patients: In first line, lenvatinib resulted non-inferior to sorafenib and it can be used as alternative, even in the lack of evidence for sequential treatment options in second line after lenvatinib. Recently, atezolizumab plus bevacizumab have shown superiority over sorafenib in first-line. Sorafenib-regorafenib sequential administration in selected patients has opened a new paradigm of treatment in advanced HCC with a life expectancy exceeding two years. Other TKIs for second line treatment include cabozantinib and ramucirumab (specifically for patients with Alpha-fetoprotein values ≥ 400 ng/mL). The combination of TKIs with immunotherapy may represent a big step forward for these patients in the near future.

Keywords: Hepatocellular carcinoma, Systemic, Options, Sequencing, Advanced, Future

Core tip: The prognosis of advanced hepatocellular carcinoma (HCC) has been improved in the last years due to new available drugs for first and second line systemic treatments. Recent improvements in HCC molecular mechanisms have led to development of effective systemic treatments including tyrosine kinase inhibitors and immunotherapy. In this review, we describe first and second line systemic treatment options for advanced HCC focusing on sequencing therapy and comparison of different second line options.