Treatment with cabozantinib was clinically active and associated with manageable toxicities in patients with advanced, recurrent, or metastatic hepatocellular carcinoma (HCC), according to a study published in Annals of Oncology.1

For the multicohort, phase 2 trial (ClinicalTrials.gov Identifier: NCT00940225), investigators enrolled adult patients with 9 different types of advanced malignancies, including 41 patients with HCC. All patients with HCC had Child-Pugh A liver function and had received no more than 1 prior systemic regimen.

All patients initially received cabozantinib at a starting dose of 100 mg daily. After an initial 12-week period of cabozantinib therapy, patients were randomly assigned to receive cabozantinib or placebo.

By week 12, 5% of patients had achieved an objective response, including 2 patients who achieved a confirmed partial response. A total of 66% of patients achieved disease control at week 12, with 73% of Asian patients having stable disease or a partial response.

Among the 22 patients with stable disease who were randomly assigned to cabozantinib or placebo, median progression-free survival from randomization was 2.5 months and 1.4 months, respectively. This difference was not statistically significant.

The study further demonstrated that median progression-free survival from day 1 of therapy in all patients was 5.2 months and median overall survival was 11.5 months.

The most frequently reported grade 3 to 4 adverse events were diarrhea, hand-foot syndrome, and thrombocytopenia. Investigators managed adverse events with dose reductions in 59% of patients.

Cabozantinib is an oral inhibitor of the tyrosine kinases MET, AXL, and VEGF receptors. The drug is approved by the U.S. Food and Drug Administration as Cometriq for patients with advanced medullary thyroid cancer and as Cabometyx for advanced kidney cancer.