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World J Gastroenterol. May 14, 2015; 21(18): 5445-5453
Published online May 14, 2015. doi: 10.3748/wjg.v21.i18.5445
MET inhibitors for treatment of advanced hepatocellular carcinoma: A review
Xing-Shun Qi, Xiao-Zhong Guo, Guo-Hong Han, Hong-Yu Li, Jiang Chen
Xing-Shun Qi, Xiao-Zhong Guo, Hong-Yu Li, Jiang Chen, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang 100840, Liaoning Province, China
Xing-Shun Qi, Guo-Hong Han, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, Shaanxi Province, China
Author contributions: Qi XS conceived this work, performed the literature search and selection, and drafted the manuscript; Guo XZ, Han GH, Li HY and Chen J gave critical comments and revised the manuscript; all authors have made an intellectual contribution to the manuscript and approved the submission.
Conflict-of-interest: All authors disclosed no conflicts of interest for this work.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
Correspondence to: Xiao-Zhong Guo, MD, PhD, Professor, Department of Gastroenterology, General Hospital of Shenyang Military Area, No. 83 Wenhua Road, Shenyang 110840, Liaoning Province, China. guo_xiao_zhong@126.com
Telephone: +86-24-28897603 Fax: +86-24-28851113
Received: December 10, 2014
Peer-review started: December 10, 2014
First decision: December 26, 2014
Revised: January 9, 2015
Accepted: February 11, 2015
Article in press: February 11, 2015
Published online: May 14, 2015
Processing time: 158 Days and 23 Hours
Abstract

The current standard treatment option for advanced hepatocellular carcinoma (HCC) is sorafenib, but its clinical benefit is modest. In spite of many attempts, few drugs can provide any significant improvement of survival as the first- or second-line therapy of choice in phase III randomized controlled trials. Recently, the subgroup analysis of a phase II randomized controlled trial has shown that tivantinib, a selective MET inhibitor, can significantly improve the overall survival in patients with MET-positive advanced HCC after the failure or intolerance of a prior systemic therapy. These findings enlighten the role of MET inhibitors in the treatment of advanced HCC. In this paper, we review all ongoing and completed clinical trials regarding this topic. As for the first-line therapy of advanced HCC, INC280 and foretinib are being evaluated in 2 phase II single-arm trials; and MSC2156119J and golvatinib plus sorafenib are being compared with sorafenib alone in 2 phase II randomized controlled trials. As for the second-line therapy of advanced HCC, tivantinib and cabozantinib are being compared with placebo in 2 phase III randomized controlled trials.

Keywords: MET; Hepatocyte growth factor; Tivantinib; Cabozantinib; INC280; MSC2156119J; Golvatinib; Foretinib

Core tip: MET inhibitors are being tested as the first-line or second-line therapy for advanced hepatocellular carcinoma after the failure of a loco-regional or systemic therapy, especially in patients with high MET expression. Ongoing phase III randomized controlled trials will provide the decisive recommendations regarding the use of MET inhibitors in advanced hepatocellular carcinoma.