MET inhibitors for treatment of advanced hepatocellular carcinoma: A review

World J Gastroenterol. 2015 May 14;21(18):5445-53. doi: 10.3748/wjg.v21.i18.5445.

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

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-met / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • MET protein, human
  • Proto-Oncogene Proteins c-met