Novel drugs in clinical development for hepatocellular carcinoma

Abstract

Introduction: Sorafenib is the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). Within recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development either due to toxicity or lack of benefit.

Areas covered: This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC.

Expert opinion: In unselected patients with advanced HCC, disappointing results have been reported from several large trials. However, in two subgroups encouraging results have been achieved. Treatment with the MET inhibitor tivantinib resulted in a substantial survival benefit in the subgroup of MET overexpressing tumors in a randomized Phase II trial. Furthermore, the vascular endothelial growth factor receptor 2 antibody ramucirumab resulted in improved overall survival in patients with baseline α-fetoprotein (AFP) ≥ 400 ng/ml in a Phase III trial. These two agents, and several others, will be further developed in HCC. Moreover, immunotherapeutics such as checkpoint inhibitors, programmed death receptor-1 blocking antibodies and oncolytic viruses are under investigation in advanced HCC.

Keywords:

• anti-CTLA-4
• anti-PD1
• cabozantinib
• everolimus
• hepatocellular carcinoma
• immunotherapy
• lenvatinib
• oncolytic virus
• ramucirumab
• receptor tyrosine kinase inhibitor
• refametinib
• regorafenib
• sorafenib
• tivantinib
• trebananib

Declaration of interest

O Waidmann has received lecture fees and is on the advisory board for Bayer Healthcare and Novartis. J Trojan is on the advisory board for Bayer Healthcare, Eli Lilly & Company, Daichi Sankyo, Novartis, Amgen Inc and Merck Serono. He also received lecture fees from Bayer Healthcare. 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.

Notes

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