title: A Phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis.
abstract: BACKGROUND
  The mesenchymal-epithelial transition factor (MET) receptor is dysregulated in hepatocellular carcinoma (HCC), and tivantinib (ARQ 197) is an oral, selective, MET inhibitor.
  
  
  METHODS
  This Phase-1b study assessed tivantinib safety as primary objective in patients with previously treated HCC and Child-Pugh A or B liver cirrhosis. Patients received oral tivantinib 360 mg twice daily until disease progression or unacceptable toxicity.
  
  
  RESULTS
  Among 21 HCC patients, common drug-related adverse events (AEs) were neutropaenia, anaemia, asthenia, leucopaenia, anorexia, diarrhoea, and fatigue. No drug-related worsening of liver function or performance status occurred, but one Child-Pugh B patient experienced drug-related bilirubin increase. Four patients had drug-related serious AEs, including one neutropaenia-related death. Haematologic toxicities were more frequent than in previous tivantinib studies but were manageable with prompt therapy. Best response was stable disease (median, 5.3 months) in 9 of 16 evaluable patients (56%). Median time to progression was 3.3 months.
  
  
  CONCLUSIONS
  Tivantinib demonstrated a manageable safety profile and preliminary antitumour activity in patients with HCC and Child-Pugh A or B cirrhosis.
authors.affiliation: Medical Oncology and Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas IRCCS, Via Manzoni 56, 20089 Rozzano (Milan), Italy.
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: M
authors.initials: M
authors.lastname: Simonelli
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez-Lope
authors.forename: P
authors.initials: P
authors.lastname: Zucali
authors.forename: L H
authors.initials: LH
authors.lastname: Camacho
authors.forename: A
authors.initials: A
authors.lastname: Granito
authors.forename: N
authors.initials: N
authors.lastname: Senzer
authors.forename: L
authors.initials: L
authors.lastname: Rimassa
authors.forename: G
authors.initials: G
authors.lastname: Abbadessa
authors.forename: B
authors.initials: B
authors.lastname: Schwartz
authors.forename: M
authors.initials: M
authors.lastname: Lamar
authors.forename: R E
authors.initials: RE
authors.lastname: Savage
authors.forename: J
authors.initials: J
authors.lastname: Bruix
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D019233:Retreatment
chemical_list: C551661:ARQ 197; D000970:Antineoplastic Agents; D011760:Pyrrolidinones; D011804:Quinolines; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met