title: Incidence and risk of hand-foot skin reaction with cabozantinib, a novel multikinase inhibitor: a meta-analysis.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: V R
authors.initials: VR
authors.lastname: Belum
authors.affiliation: Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Serna-Tamayo
authors.affiliation: Division of Medical Oncology, Department of Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA.|Division of Haematology and Oncology, Department of Medicine, Northport VA Medical Center, Northport, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.affiliation: Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Lacouture
mesh_terms: D000813:Anilides / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D060831:Hand-Foot Syndrome / Q000209:etiology*; D006801:Humans; D015994:Incidence; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011725:Pyridines / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C558660:cabozantinib