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Management of Adverse Events Associated with Cabozantinib Treatment in Patients with Advanced Hepatocellular
Gabriel Schwartz1, Julianne O Darling2, Malori Mindo3
1Gastrointestinal Medical Oncology Clinic, University of California San Francisco, 1825 Fourth St, Fourth Floor, San Francisco, CA, 94158, USA. Gabriel.Schwartz@ucsf.edu.
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.
Insights
Cabozantinib effectively manages advanced liver cancer, but common side effects like fatigue and skin reactions require attention. Early intervention with supportive care and dose adjustments improves patient tolerability and quality of life.
Area of Science:
- Oncology
- Pharmacology
Background:
- Cabozantinib is an oral multikinase inhibitor targeting VEGFR, MET, and TAM kinases.
- It is approved for advanced hepatocellular carcinoma (HCC) post-sorafenib treatment, demonstrating improved survival in the CELESTIAL trial.
Purpose of the Study:
- To review the safety profile of cabozantinib in advanced HCC patients.
- To provide guidance on managing common adverse events (AEs) associated with cabozantinib therapy.
Main Methods:
- Review of safety data from the phase III CELESTIAL study.
- Analysis of common adverse events, including palmar-plantar erythrodysesthesia, fatigue, gastrointestinal events, and hypertension.
- Inclusion of clinical experience and literature evidence for AE management.
Main Results:
- Common AEs include palmar-plantar erythrodysesthesia, fatigue, GI events, and hypertension, impacting tolerability and quality of life.
- Over half of patients required dose reduction, but treatment discontinuation rates due to AEs were low.
- AEs can be managed effectively through supportive care and dose modifications.
Conclusions:
- Cabozantinib is an effective treatment for advanced HCC, with manageable safety profile.
- Proactive management of AEs is crucial for maintaining treatment adherence and improving patient outcomes.
- Understanding factors affecting exposure and tolerability is key for optimizing cabozantinib therapy.
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