Management of Adverse Events Associated with Cabozantinib Treatment in Patients with Advanced Hepatocellular Carcinoma

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. Electronic supplementary material The online version of this article (10.1007/s11523-020-00736-8) contains supplementary material, which is available to authorized users.

Precision Medicine for Hepatocellular Carcinoma: Clinical Perspective

“…During the study, the most common events were palmar-plantar erythrodysesthesia, hypertension, increased aspartate aminotransferase levels, fatigue, and diarrhea. These AEs can be successfully managed by the adopted strategy of supportive care and dose modifications [163]. The comparative cost-effectiveness studies from Germany and the United States found that cabozantinib is not cost-effective compared to that of the best supportive care [164].…”

Cabozantinib: An evolving therapy for hepatocellular carcinoma

“…Although observational studies have reported a median initial dose of cabozantinib at 40 mg [56], clearance of cabozantinib is variable among patients; therefore, modification to the initial dose is generally not recommended except for patients using concomitant medications with potential drug-drug interactions or those with moderate hepatic impairment. The preferred dosing strategy is to initiate cabozantinib at the 60-mg dose but to implement dose reduction promptly to address tolerability, particularly in the first few months of treatment when most adverse events emerge [57].…”

Progression of Cabozantinib-Related Osteonecrosis Mimicking Metastases on Bone Scan

“…[2][3][4][5][6] There are only few reported cases of cabozantinib-related osteonecrosis of the jaw. 7,8 Cabozantinib is an oral multikinase inhibitor whose targets include vascular endothelial growth factor receptors, which might be the cause for osteonecrosis. This case demonstrates an underreported side effect of cabozantinib, which might be overlooked or mistaken for osseous metastasis but has a decisive impact on further oncological management.…”

“…Medication-related osteonecrosis of the jaw is a well-described complication of antiresorptive and antiangiogenic medications, predominantly seen in patients receiving bisphosphonate treatment, because of their combined effects on bone remodeling and angiogenesis 2–6 . There are only few reported cases of cabozantinib-related osteonecrosis of the jaw 7,8 . Cabozantinib is an oral multikinase inhibitor whose targets include vascular endothelial growth factor receptors, which might be the cause for osteonecrosis.…”