Cabozantinib in patients with hepatocellular carcinoma failing previous treatment with sorafenib

Over the past 10 years, sorafenib has been the only systemic agent approved for the treatment of patients with unresectable hepatocellular carcinoma. Recently, lenvatinib was demonstrated noninferior to sorafenib, and regorafenib and ramucirumab were demonstrated superior to placebo in patients progressing on sorafenib and in patients with elevated α-fetoprotein-failing sorafenib, respectively. Phase I–II trials of immune checkpoint inhibitors reported promising efficacy signals. Recently, the randomized, placebo-controlled, Phase III CELESTIAL trial demonstrated statistically and clinically significant increase in overall survival from 8 months with placebo to 10.2 months with cabozantinib in patients failing sorafenib. Furthermore, the study showed a significant improvement in all the efficacy end points. Main adverse events were palmar–plantar erythrodysesthesia, hypertension, increased aspartate aminotransferase, fatigue and diarrhea.