Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma

Abstract

Cabozantinib is an oral tyrosine-kinase inhibitor whose targets include VEGFR, MET, and AXL. Cabozantinib is approved for the treatment of patients with advanced clear-cell renal-cell carcinoma (RCC) who have received prior antiangiogenic therapy. In the pivotal Phase III trial of second-line RCC, cabozantinib was associated with a significant improvement in overall survival, progression-free survival, and antitumor response compared with everolimus. Adverse events (AEs) were common for patients receiving cabozantinib, but were effectively managed with supportive care and dose modifications, as discontinuations of cabozantinib due to an AE were infrequent. This article reviews the management of the more common AEs associated with cabozantinib based on findings from the pivotal study, clinical practice guidelines, and the authors’ real-world clinical experience, with support from published literature. We focus on hypertension, palmar–plantar erythrodysesthesia, diarrhea, nausea, vomiting, decreased appetite, fatigue, and stomatitis. Effective management of these AEs involves a multimodal strategy that includes patient education, prophylactic and supportive care, and dose modifications. Effective AE management can allow patients to maintain antitumor activity with cabozantinib while mitigating the impact on quality of life.

Keywords:

• cabozantinib
• adverse-event management
• renal-cell carcinoma
• targeted therapy
• tyrosine-kinase inhibitors

Acknowledgments

Medical writing and editorial assistance were provided by Christin Chong, PhD and Michael Raffin of Fishawack Communications (Conshohocken, PA). Funding for this work was provided by Exelixis Inc (South San Francisco, CA).

Author contributions

Both authors contributed to study conception/design, provision of study material/patients, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of the manuscript.

Disclosure

BG has received honoraria from Exelixis, and PAC has received honoraria from Pfizer and Exelixis. The authors report no other conflicts of interest in this work.