Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives
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REVIEW ARTICLE
Cabozantinib for the Treatment of Advanced Hepatocellular Carcinoma: Current Data and Future Perspectives Jörg Trojan1
© The Author(s) 2020
Abstract 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, placebocontrolled, 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.
Key Points Cabozantinib is approved for patients with sorafenibpretreated advanced hepatocellular carcinoma (HCC). The management of hypertension and gastrointestinal and dermatological toxicity is crucial to maximize the benefit of this targeted therapy in HCC. Cabozantinib is currently being further developed in combination with immune checkpoint inhibitors in patients with advanced HCC.
1 Introduction Liver cancer is the fourth most frequent cause of cancerrelated mortality, with 782,000 deaths in 2018 worldwide [1]. The most common form of liver cancer is hepatocellular * Jörg Trojan [email protected]‑frankfurt.de 1
Universitätsklinikum Frankfurt, Medizinische Klinik 1, Theodor‑Stern‑Kai 7, 60590 Frankfurt am Main, Germany
carcinoma (HCC), with over 600,000 new cases annually. Most cases of HCC occur in Asia and sub-Saharan Africa due to endemic chronic hepatitis B virus infection. In Western countries, alcohol and chronic hepatitis C virus infection are the predominant risk factors, and due to rising prevalence of non-alcoholic steatohepatitis, the incidence of HCC is steadily rising. Most patients with HCC have underlying liver cirrhosis, which not only limits surgical options, but also might result in different safety profiles of systemic agents. Despite new therapeutic options, HCC is an aggressive condition and patients with advanced disease have a poor prognosis [2]. The landscape of systemic therapy for advanced HCC has been evolving rapidly since 2017. For 10 years, the multi-targeted antiangiogenic tyrosine kinase inhibitor sorafenib was the only approved systemic therapy [3, 4]. After 2017, the multi-targeted tyrosine kinase inhibitor
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