On January 14, 2019, the FDA approved cabozantinib (Cabometyx; Exelixis) an oral multitargeted tyrosine kinase inhibitor, for the treatment of patients with hepatocellular carcinoma who were previously treated with sorafenib (Nexavar).
This approval was based on a phase 3, randomized, double-blind, multicenter clinical trial of 707 patients with previously treated hepatocellular carcinoma who had Child-Pugh Class A liver impairment. Patients were randomized in a 2:1 ratio to oral cabozantinib 60 mg daily or placebo until disease progression or unacceptable toxicity.
Median overall survival, the primary end point of the trial, was 10.2 months (95% confidence interval [CI], 9.1-12.0) for patients receiving cabozantinib versus 8 months (95% CI, 6.8-9.4) for those receiving placebo (hazard ratio [HR] 0.76; 95% CI, 0.63-0.92; P = .0049). The median progression-free survival was 5.2 months (95% CI, 4.0-5.5) for the cabozantinib treatment group versus 1.9 months (95% CI, 1.9-1.9) for the placebo group (HR, 0.44; 95% CI, 0.36-0.52; P <.001). The overall response rate was 4% in the cabozantinib group versus 0.4% in the placebo group.
The most common (≥25%) adverse events reported with cabozantinib were diarrhea, fatigue, decreased appetite, palmar-plantar erythrodysesthesia, nausea, hypertension, and vomiting.