Treatment with tivantinib produced a 56% improvement in time-to-progression (TTP) in patients with hepatocellular carcinoma (HCC) (hazard ratio = 0.64; P
= .04), according to information released by ArQule, which is developing tivantinib.
Tivantinib is an experimental selective inhibitor of c-Met, a receptor tyrosine kinase, which is given orally. In some cancer cells, c-Met plays multiple roles, including cell growth, survival, angiogenesis, invasion, and metastasis.
The 107 patients in this randomized, controlled phase II trial had unresectable HCC and had experienced disease progression after first-line therapy or were unable to tolerate such therapy. HCC is the most common primary cancer of the liver.
At the start of the study, patients were randomized to receive 360 mg BID of tivantinib or placebo. Due to the rate of neutropenia, the tivantinib dose was reduced to 240 mg BID for all patients in the treatment arm.
TTP was defined as the time from patient randomization until objective tumor progression using RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria evaluated by radiologists.
Adverse events were similar in the treatment and placebo arms, except for a higher incidence of fatigue and hematologic events, including neutropenia and anemia, in tivantinib-treated patients. The incidence of hematologic events declined after the dose reduction.