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Combination Antiangiogenic and Immunotherapy for Advanced Hepatocellular Carcinoma: Evidence to Date

Authors Raybould AL, Sanoff H

Received 24 April 2020

Accepted for publication 30 July 2020

Published 15 September 2020 Volume 2020:7 Pages 133—142


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Ahmed Kaseb

Alison L Raybould, Hanna Sanoff

Department of Medicine, Division of Hematology-Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

Correspondence: Alison L Raybould Division of Hematology/Oncology, Physicians Office Building, 3rd Floor, 170 Manning Drive, CB #7305, Chapel Hill, NC 27599, USA
Tel +1-919-966-4431
Fax +1-919-966-6735

Abstract: For over a decade, sorafenib remained the only systemic agent with proven clinical efficacy for patients with advanced hepatocellular carcinoma (HCC). Recent years have seen a proliferation of agents. In the first line, lenvatinib was found to be non-inferior to sorafenib in terms of overall survival (OS), with significantly better progression-free survival and objective response rate. Meanwhile, encouraging efficacy signals were observed in phase I/II studies of immune checkpoint inhibitors as monotherapy in HCC. Although subsequent phase III trials failed to demonstrate statistically significant benefit in OS, other clinically meaningful outcomes were observed, including long-term disease control with a favorable toxicity profile. In addition, a synergistic response has been postulated based on the interplay between antiangiogenic molecular targeted agents and immunotherapy. On this basis, interest has turned toward combination strategies of immunotherapy with these standard-of-care medications in the hope of improving treatment efficacy for advanced HCC, while maintaining tolerable safety profiles. Indeed, preliminary results from phase I studies of lenvatinib plus pembrolizumab and atezolizumab plus bevacizumab have proved favorable, prompting phase III investigations in the frontline setting, and for atezolizumab plus bevacizumab, these positive findings have been substantiated by recent reporting of phase III data from IMbrave150. In this review, we will present the currently available data on combination therapy atezolizumab plus bevacizumab in advanced HCC, and compare these findings to other promising combination treatments, most notably that of lenvatinib plus pembrolizumab.

Keywords: advanced hepatocellular carcinoma, combination therapy, antiangiogenic treatment, immunotherapy

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