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Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma
Article first published online: 25 JUL 2012
Copyright © 2012 American Cancer Society
Volume 119, Issue 2, pages 380–387, 15 January 2013
How to Cite
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., Qian, J., Scappaticci, F. A., Ricker, J. L., Carlson, D. M. and Yong, W. P. (2013), Phase 2 trial of linifanib (ABT-869) in patients with unresectable or metastatic hepatocellular carcinoma. Cancer, 119: 380–387. doi: 10.1002/cncr.27758
- Issue published online: 4 JAN 2013
- Article first published online: 25 JUL 2012
- Manuscript Accepted: 11 JUN 2012
- Manuscript Revised: 6 JUN 2012
- Manuscript Received: 16 APR 2012
- hepatocellular carcinoma (HCC);
- platelet-derived growth factor receptor (PDGFR);
- vascular endothelial growth factor receptor (VEGFR);
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.
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.
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.
Single-agent linifanib was found to be clinically active in patients with advanced hepatocellular carcinoma, with an acceptable safety profile. Cancer 2013. © 2012 American Cancer Society.