MET inhibitors for treatment of advanced hepatocellular carcinoma: A review

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC), but offers limited clinical benefit.
• Few therapies have demonstrated significant survival improvements in first- or second-line treatments for advanced HCC.
• The role of MET inhibitors in advanced HCC treatment is an emerging area of research.

Purpose of the Study:

• To review ongoing and completed clinical trials of MET inhibitors for advanced hepatocellular carcinoma (HCC).
• To evaluate the efficacy of MET inhibitors as both first-line and second-line therapies for advanced HCC.
• To highlight the potential of targeted therapies in improving outcomes for HCC patients.

Main Methods:

• Systematic review of clinical trials investigating MET inhibitors in advanced HCC.
• Analysis of data from phase II and phase III randomized controlled trials.
• Inclusion of single-arm trials evaluating first-line therapies and randomized controlled trials for first- and second-line treatments.

Main Results:

• Tivantinib, a MET inhibitor, demonstrated significant overall survival improvement in MET-positive advanced HCC patients post-systemic therapy failure.
• Several MET inhibitors (INC280, foretinib, MSC2156119J, golvatinib) are under investigation in phase II trials for first-line HCC therapy.
• Tivantinib and cabozantinib are being evaluated against placebo in phase III trials for second-line advanced HCC treatment.

Conclusions:

• MET inhibitors represent a promising therapeutic strategy for advanced hepatocellular carcinoma (HCC).
• Targeting MET may offer improved survival benefits for specific HCC patient subgroups.
• Further clinical trials are crucial to establish the role of MET inhibitors in HCC treatment paradigms.