Dr. Abou-Alfa on MET Inhibition in Liver Cancer

Ghassan K. Abou-Alfa, MD, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, discusses the promising results and future investigation of MET inhibition in hepatocellular carcinoma (HCC) using cabozantinib (Cometriq) and tivantinib (ARQ 197).

Cabozantinib, a multikinase inhibitor that blocks both VEGFR2 and MET, demonstrated impressive results in a phase II trial, Abou-Alfa notes. Overall, the randomized discontinuation trial included 41 patients and found that treatment with cabozantinib improved median overall survival (OS) by 15.1 months.

The most promising results for tivantinib, a selective inhibitor of MET, has evolved around MET expression as a prognostic factor, Abou-Alfa believes. In a phase II trial, 107 patients with HCC were treated with tivantinib or placebo. The most promising results were in patients with MET-positive tumors. These patients experienced more than a doubling in OS compared to placebo, from 3.8 months to 7.2 (HR = 0.38; P = 0.01).

Given the positive phase II results, phase III trials investigating these two agents are likely. The phase III trial examining tivantinib was announced January 31, 2013. This trial will select patients based on MET expression, which makes sense given previous results with the agent, Abou-Alfa notes. However, cabozantinib as a multikinase inhibitor may not benefit from this type of trial design, since MET expression has not been validated.