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

Abstract

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 360 mg 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.

• Authors: A Santoro, M Simonelli, C Rodriguez-Lope, P Zucali, L H Camacho, A Granito, N Senzer, L Rimassa, G Abbadessa, B Schwartz, M Lamar, R E Savage, J Bruix
• Journal: British journal of cancer (Br J Cancer) Vol. 108 Issue 1 Pg. 21-4 (Jan 15 2013) ISSN: 1532-1827 [Electronic] England
• PMID: 23287988 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ARQ 197
• Antineoplastic Agents
• Pyrrolidinones
• Quinolines
• MET protein, human
• Proto-Oncogene Proteins c-met

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Carcinoma, Hepatocellular (complications, drug therapy)
• Female
• Humans
• Liver Cirrhosis (complications)
• Liver Neoplasms (complications, drug therapy)
• Male
• Middle Aged
• Proto-Oncogene Proteins c-met (antagonists & inhibitors)
• Pyrrolidinones (adverse effects, therapeutic use)
• Quinolines (adverse effects, therapeutic use)
• Retreatment