A Phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis

作者：Santoro A; Simonelli M; Rodriguez Lope C; Zucali P; Camacho L H; Granito A; Senzer N; Rimassa L; Abbadessa G; Schwartz B; Lamar M; Savage R E; Bruix J^*

来源：British Journal of Cancer, 2013, 108(1): 21-24.

DOI：10.1038/bjc.2012.556

• hepatocellular carcinoma
• liver cirrhosis
• liver function
• MET inhibitor
• tivantinib

Background: The mesenchymal-epithelial transition factor (MET) receptor is dysregulated in hepatocellular carcinoma (HCC), and tivantinib (ARQ 197) is an oral, selective, MET inhibitor.
Methods: This Phase-1b study assessed tivantinib safety as primary objective in patients with previously treated HCC and Child-Pugh A or B liver cirrhosis. Patients received oral tivantinib 360mg twice daily until disease progression or unacceptable toxicity.
Results: Among 21 HCC patients, common drug-related adverse events (AEs) were neutropaenia, anaemia, asthenia, leucopaenia, anorexia, diarrhoea, and fatigue. No drug-related worsening of liver function or performance status occurred, but one Child-Pugh B patient experienced drug-related bilirubin increase. Four patients had drug-related serious AEs, including one neutropaenia-related death. Haematologic toxicities were more frequent than in previous tivantinib studies but were manageable with prompt therapy. Best response was stable disease (median, 5.3 months) in 9 of 16 evaluable patients (56%). Median time to progression was 3.3 months.
Conclusion: Tivantinib demonstrated a manageable safety profile and preliminary antitumour activity in patients with HCC and Child-Pugh A or B cirrhosis.

• 出版日期2013-1-15