title: Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma.
abstract: BACKGROUND
  The efficacy and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinases, were assessed in this phase 2, single-arm, open-label, multicenter trial.
  
  
  METHODS
  Eligible patients had unresectable or metastatic hepatocellular carcinoma and had received ≤ 1 prior systemic therapy. Patients received oral linifanib at a fasting dose of 0.25 mg/kg,. The primary endpoint was the progression-free rate at 16 weeks. Tumor response was assessed every 8 weeks. Secondary endpoints included the time to disease progression, overall survival, and objective response rate. Safety was also assessed.
  
  
  RESULTS
  Of the 44 patients enrolled, the majority were Asian (89%), had received no prior systemic therapy (82%), had Child-Pugh class A hepatic function (86%), and had hepatitis B virus infection (61%). The estimated progression-free rate at 16 weeks was 31.8% (34.2% for patients with Child-Pugh class A hepatic function), the estimated objective response rate was 9.1% (10.5% for patients with Child-Pugh class A hepatic function), the median time to disease progression was 3.7 months (3.7 months for patients with Child-Pugh class A hepatic function), and the median overall survival was 9.7 months (10.4 months for patients with Child-Pugh class A hepatic function). The most common linifanib-related adverse events were diarrhea (55%) and fatigue (52%). The most common linifanib-related grade 3/4 adverse events were hypertension (25%) and fatigue (14%). Serum levels of biomarkers cancer antigen (CA) 125, cytokeratin fragment (CYFRA)21.1, and protein induced by vitamin K absence or antagonist II (PIVKA) demonstrated potential as prognostic indicators of patient response or outcome.
  
  
  CONCLUSIONS
  Single-agent linifanib was found to be clinically active in patients with advanced hepatocellular carcinoma, with an acceptable safety profile.
authors: Department of Medical Oncology, National Cancer Centre Singapore, Singapore. hanchongtoh@gmail.com
authors: Han Chong
authors: HC
authors: Toh
authors: Pei-Jer
authors: PJ
authors: Chen
authors: Brian I
authors: BI
authors: Carr
authors: Jennifer J
authors: JJ
authors: Knox
authors: Sharlene
authors: S
authors: Gill
authors: Peter
authors: P
authors: Ansell
authors: Evelyn M
authors: EM
authors: McKeegan
authors: Barry
authors: B
authors: Dowell
authors: Michelle
authors: M
authors: Pedersen
authors: Qin
authors: Q
authors: Qin
authors: Jiang
authors: J
authors: Qian
authors: Frank A
authors: FA
authors: Scappaticci
authors: Justin L
authors: JL
authors: Ricker
authors: Dawn M
authors: DM
authors: Carlson
authors: Wei Peng
authors: WP
authors: Yong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D006801:Humans; D007191:Indazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007191:Indazoles; D010671:Phenylurea Compounds; C513486:linifanib