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Profile of tivantinib and its potential in the treatment of hepatocellular carcinoma: the evidence to date

Authors Pievsky D, Pyrsopoulos N

Received 8 September 2016

Accepted for publication 14 October 2016

Published 15 November 2016 Volume 2016:3 Pages 69—76


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Professor Ahmed O Kaseb

Daniel Pievsky,1 Nikolaos Pyrsopoulos2

1Department of Internal Medicine, 2Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, University Hospital, Newark, NJ, USA

Abstract: Hepatocellular carcinoma (HCC) is the fastest rising cause of cancer-related death in the United States and carries a very poor prognosis, with a median survival time of <50% at 1 year for advanced disease. To date, sorafenib is the only therapy approved by the Food and Drug Administration for the treatment of advanced HCC. Tivantinib (ARQ-197), a non-ATP competitive inhibitor of cellular mesenchymal–epithelial transcription factor (c-MET), has shown a survival benefit in patients with advanced HCC who have failed or are intolerant to sorafenib in Phase I and II trials. Those patients who have tumors with high concentrations of MET (MET-high) appear to derive the greatest benefit from tivantinib therapy. Currently, two large randomized double-blind placebo-controlled Phase III trials (METIV-HCC [NCT01755767] and JET-HCC [NCT02029157]) are evaluating tivantinib in patients with MET-high advanced HCC, with the primary end points of overall survival and progression-free survival, respectively. This study reviews the evidence for the use of tivantinib in advanced HCC. Specific topics addressed include the pharmacology, dosing, toxicity, and biomarkers associated with tivantinib use.

Keywords: tivantinib, ARQ-197, hepatocellular carcinoma, met inhibitor

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