Management of Adverse Events Associated with Cabozantinib Treatment in Patients with Advanced Hepatocellular Carcinoma
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THERAPY IN PRACTICE
Management of Adverse Events Associated with Cabozantinib Treatment in Patients with Advanced Hepatocellular Carcinoma Gabriel Schwartz1 · Julianne O. Darling2 · Malori Mindo3 · Lucia Damicis4
© The Author(s) 2020
Abstract Cabozantinib is an oral multikinase inhibitor whose targets include vascular endothelial growth factor receptors, MET, and the TAM family of kinases (TYRO3, AXL, MER). Cabozantinib is approved for patients with advanced hepatocellular carcinoma who have been previously treated with sorafenib, based on improved overall survival and progression-free survival relative to placebo in the phase III CELESTIAL study. During CELESTIAL, the most common adverse events (AEs) experienced by patients receiving cabozantinib included palmar-plantar erythrodysesthesia, fatigue, gastrointestinal-related events, and hypertension. These AEs can significantly impact treatment tolerability and patient quality of life. However, AEs can be effectively managed with supportive care and dose modifications. During CELESTIAL, more than half of the patients receiving cabozantinib required a dose reduction, while the rate of treatment discontinuation due to AEs was low. Here, we review the safety profile of cabozantinib and provide guidance on the prevention and management of the more common AEs, based on current evidence from the literature as well as our clinical experience. We consider the specific challenges faced by clinicians in treating this patient population and discuss factors that may affect exposure and tolerability to cabozantinib.
1 Introduction There has been a marked increase in liver cancer deaths in recent years. In 2018, there were ~ 841,000 new cases of liver cancer worldwide, and liver cancer accounted for almost 800,000 deaths, making it the sixth most prevalent cancer worldwide [1]. The most common primary malignancy of the liver is hepatocellular carcinoma (HCC) [2]. The frequency, burden, and etiology of HCC vary across geographic regions and populations but are linked to prevalence of predisposing chronic hepatic conditions such as Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11523-020-00736-8) contains supplementary material, which is available to authorized users. * Gabriel Schwartz [email protected] 1
Gastrointestinal Medical Oncology Clinic, University of California San Francisco, 1825 Fourth St, Fourth Floor, San Francisco, CA 94158, USA
2
Indiana University Health Simon Cancer Center, Indianapolis, IN, USA
3
Department of Medicine, University of California San Francisco, San Francisco, CA, USA
4
IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy
Key Points Cabozantinib represents a treatment option for patients with advanced hepatocellular carcinoma who progress after sorafenib. Adverse events associated with cabozantinib may be effectively managed with supportive care and dose modifications, thereby allowing patients to continue treatment at the appropriate dose, with minimum interruptio
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