Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma
Journal
Cancer
Journal Volume
119
Journal Issue
2
Pages
380-387
Date Issued
2013
Author(s)
Toh H.C.
Carr B.I.
Knox J.J.
Gill S.
Ansell P.
McKeegan E.M.
Dowell B.
Pedersen M.
Qin Q.
Qian J.
Scappaticci F.A.
Ricker J.L.
Carlson D.M.
Yong W.P.
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.
Subjects
angiogenesis; hepatocellular carcinoma (HCC); linifanib; platelet-derived growth factor receptor (PDGFR); sorafenib; vascular endothelial growth factor receptor (VEGFR)
SDGs
Other Subjects
CA 125 antigen; cytokeratin fragment 21.1; decarboxyprothrombin; keratin; linifanib; tumor marker; unclassified drug; adult; aged; alanine aminotransferase blood level; anemia; article; Asian; aspartate aminotransferase blood level; bedtime dosage; bilirubin blood level; cancer growth; cancer prognosis; cancer survival; Child Pugh score; clinical article; decreased appetite; diarrhea; drug efficacy; drug eruption; drug safety; fatigue; female; hand foot syndrome; human; hypertension; leukopenia; liver cell carcinoma; liver function; male; metastasis potential; multicenter study; neutropenia; open study; overall survival; phase 2 clinical trial; priority journal; progression free survival; protein blood level; proteinuria; side effect; systemic therapy; thrombocytopenia; treatment response; vomiting
Publisher
John Wiley and Sons Inc.
Type
journal article