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. Cancer 2013. © 2012 American Cancer Society.

Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

“…Linifanib (ABT-869), a multitargeted tyrosine kinase inhibitor, inhibits the members of the VEGFR and PDGFR families [34] . Linifanib as single agent showed clinical antitumor activity in OS (9.7 mo) and TTP (3.7 mo) [35] . ABT-869 appeared to benefit HCC patients, with an acceptable safety profile.…”

Management of Hepatocellular Carcinoma: An Update at the Start of 2014

“…Interim Phase II results in patients with advanced HCC showed a median TTP of 3.7 months with ABT-869 treatment and a safety profile consistent with angiogenesis inhibition. In the Toh et al study, the authors demonstrate that linifanib as a single agent was found to be clinically active in patients with advanced HCC, with an acceptable safety profile [48].…”

“…Linifanib[ABT-869] is a multitargeted tyrosine kinase inhibitor that inhibits multiple members of the VEGFR and PDGFR families [48]. In a xenograft model of HCC, ABT-869 significantly reduced tumor burden.…”

Current status and future prospects of chemotherapy for advanced hepatocellular carcinoma

“…Linifanib is a dual TKI for VEGFR and PDGFR.In a phase II trial, the results were as follows: median PFS, 3.7 months; median OS, 9.7 months [23]. In the LIGHT phase III trial of linifanib as a first-line drug, the median OS was 9.1 months with linifanib and 9.8 months with sorafenib (HR 1.05, 95 % CI 0.90-1.22, NS), which indicated that linifanib was neither superior nor inferior to sorafenib [24].…”