Incidence and risk of hand–foot skin reaction with cabozantinib, a novel multikinase inhibitor: a meta‐analysis

Summary 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.