(ChemotherapyAdvisor) – Tivantinib increases time to tumor progression (TTP) and survival in patients with Met-positive hepatocellular carcinoma (HCC), according to the results of a phase 2 study presented at the 2012 Association for Clinical Oncology. The abstract was entitled “Tivantinib (ARQ 197) versus placebo in patients (Pts) with hepatocellular carcinoma (HCC) who failed one systemic therapy: Results of a randomized controlled phase II trial (RCT).”

Tivantinib (T) inhibits c-Met, the tyrosine kinase receptor involved in tumor cell migration, invasion, proliferation and angiogenesis in hepatocellular carcinoma (HCC). Tivantinib has shown promising results in HCC in phase 1 studies as monotherapy and in combination with sorafenib, noted lead author Lorenza Rimassa, MD, Deputy Director, Medical Oncology Unit, Humanitas Cancer Center, Milan, Italy. 

In this multi-center, randomized, controlled study, patients were randomized to oral tivantinib [360mg, twice a day (A), 240mg twice a day, (B) or placebo (P). The primary end point was TTP, secondary end points included disease control rate (DCR), PFS, OS, efficacy in Met-positive patients, and safety.

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The investigators reported that major TTP, DCR and PFS benefits were obtained in Met+ pts, with preliminary OS positively trending in the tivantinib arm (HR=0.47) and no detrimental effect in Met- pts. The most common drug-related adverse events were neutropenia (25.4%) and anemia (15.5%).

The investigators concluded that, compared to placebo, tivantinib significantly benefited second-line HCC patients, especially if they were Met-positive, with a manageable safety profile at 240mg twice a day.