title: New chemical treatment options in second-line hepatocellular carcinoma: what to do when sorafenib fails?
abstract: There have been no therapies available for patients who experience disease progression after sorafenib treatment. Regorafenib inhibits multiple kinases involved in tumor proliferation and neoangiogenesis, which has produced a survival benefit in hepatocellular carcinoma (HCC) after sorafenib failure. Other active candidate agents are c-Met inhibitors and immune checkpoint inhibitors. Areas covered: This paper presents an updated summary of the preclinical and clinical experience with regorafenib, c-Met inhibitors (tivantinib, cabozantinib and tepotinib), and a checkpoint inhibitor (nivolumab, pembrolizumab) in HCC. The reported data were obtained from abstracts of international conferences and journal articles published up to August 2016 and found in a PubMed search. Expert opinion: Based on favorable data from preclinical and clinical trials, regorafenib, c-Met inhibitor, and checkpoint inhibitors are promising agents for HCC after sorafenib failure. However, further efforts to maximize the survival benefit and minimize adverse events of these drugs in the treatment of HCC are still necessary. Additionally, searching for predictors of good responders could allow these new drugs to be applied in personalized treatments of HCC.
authors.affiliation: a Department of Internal Medicine, College of Medicine , Pusan National University and Medical Research Institute, Pusan National University Hospital , Busan , Republic of Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Woo
authors.affiliation: b BIO-IT Foundry Technology Institute , Pusan National University , Busan , Republic of Korea.|c Research Institute for Convergence of Biomedical Science and Technology , Pusan National University Yangsan Hospital , Yangsan , Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Yoo
authors.affiliation: a Department of Internal Medicine, College of Medicine , Pusan National University and Medical Research Institute, Pusan National University Hospital , Busan , Republic of Korea.
authors.forename: Jeong
authors.initials: J
authors.lastname: Heo
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D019859:Proto-Oncogene Proteins c-met
keywords: Cabozantinib; c-Met inhibitor; hepatocellular carcinoma; immune checkpoint inhibitor; nivolumab; pembrolizumab; regorafenib; sorafenib; tepotinib; tivantinib