**2.4. Cabozantinib**

Cabozantinib is another inhibitor of several receptor tyrosine kinases, including the hepatocyte growth factor/c-MET and VEGFR [14]. Efficacy in patients with previously treated advanced HCC was shown in the placebo-controlled phase III CELESTIAL trial [15]. In a preliminary report, in the group of patients receiving second- or third-line treatment, median overall survival was significantly better with cabozantinib (10.2 vs. 8.0 months), and the difference was more pronounced when the analysis was limited to patients whose only prior therapy was sorafenib (median overall survival 11.3 vs. 7.2 months). The most common grade 3 or 4 adverse events with cabozantinib were palmar-plantar erythrodysesthesia (17 vs. 0 in the placebo group), hypertension (16 vs. 0%), increased aspartate aminotransferase (12 vs. 7%), fatigue (10 vs. 4%), and diarrhea (10 vs. 2%).
