Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma

Cancer. 2013 Jan 15;119(2):380-7. doi: 10.1002/cncr.27758. Epub 2012 Jul 25.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / secondary
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • Fatigue / chemically induced
  • Female
  • Humans
  • Indazoles / adverse effects
  • Indazoles / pharmacology
  • Indazoles / therapeutic use*
  • Kaplan-Meier Estimate
  • Liver Neoplasms / blood
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacology
  • Phenylurea Compounds / therapeutic use*
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Young Adult

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Indazoles
  • N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N1-(2-fluoro-5-methylphenyl)urea
  • Phenylurea Compounds