Abstract
BACKGROUND: Cabozantinib is approved in the treatment of progressive, metastatic medullary thyroid cancer (MTC). It is a small molecule inhibitor, which targets multiple receptors, including vascular endothelial growth factor receptor, tyrosine kinase with Ig and epidermal growth factor homology domains-2 and the proto-oncogenes MET (mesenchymal-epithelial transition factor) and RET (rearranged during transfection). The drug is currently in phase I/II/III clinical trials for a number of other solid tumours and haematological malignancies. The adverse event (AE) profile is similar to that of other newer angiogenesis inhibitors. Hand-foot skin reaction (HFSR) is an important dose-limiting dermatological adverse event of this class of drugs. AIM: To ascertain the incidence and risk of HFSR in patients with cancer during treatment with cabozantinib. METHODS: Electronic databases (PubMed, Web of Science) and the American Society of Clinical Oncology Meeting Library were queried from inception to July 2014. Only phase II/III studies investigating cabozantinib for the treatment of cancer were shortlisted. The incidence, relative risk (RR) and 95% CI were calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. RESULTS: We included 831 patients treated with cabozantinib for various solid malignancies in the analysis. The overall incidence was 35.3% (95% CI 27.9-43.6%) for all-grade and 9.5% (95% CI 7.6-11.7%) for high-grade HFSR. The RR of all-grade and high-grade HFSR with cabozantinib, compared with controls, was increased for both all-grade (27.3; 95% CI 6.9-108.3; P < 0.001) and high-grade (28.1; 95% CI 1.7-457; P < 0.02) HFSR, respectively. CONCLUSIONS: The incidence and risk of developing HFSR with cabozantinib are high. Timely recognition of this dose-limiting AE is critical to direct supportive care efforts including patient counselling, and to institute preventative and/or treatment interventions.