Cabozantinib for the treatment of advanced hepatocellular carcinoma: current data and future perspectives

Cabozantinib (Cabometyx®) is a potent multikinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor 2, the mesenchymal-epithelial transition factor (MET) receptor, and the “anexelekto” (AXL) receptor tyrosine kinase. It is approved for the treatment of advanced hepatocellular carcinoma (HCC) after failure of sorafenib in Europe (since November 2018) and in the USA (since January 2019). The approval of cabozantinib was based on results of the randomized, placebo-controlled, phase 3 CELESTIAL trial in patients with unresectable HCC, who received one or two prior lines of treatment including sorafenib. At the second planned interim analysis, the trial was stopped, because the primary end point overall survival was clearly in favor for cabozantinib. Additionally, median progression-free survival was superior to placebo. The most common ≥ grade 3 relevant adverse events in patients with HCC treated with cabozantinib were palmar–plantar erythrodysesthesia, hypertension, fatigue, and diarrhea. In this review, current data on cabozantinib for the treatment of patients with advanced HCC, with a focus on the management of common adverse events and ongoing clinical trials, are discussed.