Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma
Toh, H.C. Chen, P.-J. Carr, B.I. Knox, J.J. Gill, S. Ansell, P. McKeegan, E.M. Dowell, B. Pedersen, M. Qin, Q.
Toh, H.C.
Chen, P.-J.
Carr, B.I.
Knox, J.J.
Gill, S.
Ansell, P.
McKeegan, E.M.
Dowell, B.
Pedersen, M.
Qin, Q.
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Alternative Title
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. © 2012 American Cancer Society.
Keywords
angiogenesis, hepatocellular carcinoma (HCC), linifanib, platelet-derived growth factor receptor (PDGFR), sorafenib, vascular endothelial growth factor receptor (VEGFR)
Source Title
Cancer
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Series/Report No.
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Date
2013-01-15
DOI
10.1002/cncr.27758
Type
Article