Emerging tyrosine kinase inhibitors for the treatment of hepatocellular carcinoma

ABSTRACT

Introduction: Hepatocellular carcinoma (HCC) is the fifth most diagnosed cancer in the world and the third leading cause of death. Unfortunately, when diagnosed two thirds of patients have an advanced disease for which only palliative treatment can be proposed and most likely systemic therapy.

Areas covered: As of today only one systemic therapy is validated in the treatment of advanced HCC, a tyrosine kinase inhibitor (TKI): Sorafenib. Treatment options are therefore lacking. With the advent of Sorafenib other TKIs have been studied with some disappointing results. Many explanations can be found to the failure of these tested TKIs such as the underlying cirrhosis leading to rapidly serious adverse events, or trial design imperfections.

Expert opinion: Taking into account these failures, new trials with more appropriate designs have led to recent success with multi-target TKIs (Regorafenib and Lenvatinib). This multi-target approach allows to overcome the molecular heterogeneity of advanced HCC which is associated with multiple simultaneously dysregulated signaling pathways. On the contrary, another lead is to study target a specific TKI such as c-MET inhibitors or TGFβR inhibitors in HCC sub-populations with promising results in early phase trials. These results will have to be validated in the ongoing phase III trials.

KEYWORDS:

• Hepatocellular carcinoma
• tyrosine kinase inhibitors
• sorafenib
• regorafenib
• lenvatinib
• c-MET inhibitors
• multi-target kinases inhibitors

Declaration of interest

JF Blanc has received honoraria from Bayer, Lilly Oncology, Bristol-Myers Squibb and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded