title: Novel drugs in clinical development for hepatocellular carcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This review covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Universitätsklinikum Frankfurt, Medizinische Klinik 1 , Theodor-Stern-Kai 7, Frankfurt am Main , Germany +49 0 69 6301 7860 ; +49 0 69 6301 6448 ; trojan@em.uni-frankfurt.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Waidmann
authors.forename: Jörg
authors.initials: J
authors.lastname: Trojan
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D000077157:Sorafenib
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: anti-CTLA-4; anti-PD1; cabozantinib; everolimus; hepatocellular carcinoma; immunotherapy; lenvatinib; oncolytic virus; ramucirumab; receptor tyrosine kinase inhibitor; refametinib; regorafenib; sorafenib; tivantinib; trebananib