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