Incidence and risk of hypertension associated with cabozantinib in cancer patients: a systematic review and meta-analysis

Expert Rev Clin Pharmacol. 2016 Aug;9(8):1109-15. doi: 10.1080/17512433.2016.1190269. Epub 2016 Jun 1.

Abstract

Introduction: Cabozantinib (XL184) is an oral inhibitor of multiplereceptor tyrosine kinases including mesenchymal-epithelial transition factor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2). Hypertension is one of its major side effects, but the incidence rate and overall risk has not been systematically studied. We thus conducted this meta-analysis to investigate the overall incidence and risk of developing hypertension in cancer patients treated with cabozantinib.

Areas covered: Pubmed, Embase and oncology conference proceedings were searched for relevant studies. Eligible studies were phase II and III prospective clinical trials of cabozantinib in cancer patients with data on hypertension available. A total of 1,514 patients (cabozantinib, 1083; control, 431) with a variety of solid tumors from 8 prospective clinical trials were included for the meta-analysis. The use of cabozantinib was associated with significantly increased risk of developing all grade (RR 5.48; 95%CI, 3.76-7.99; p < 0.001) and high grade (5.09; 95% CI: 2.71-9.54, p < 0.001) hypertension in comparison with controls. Additionally, the risk of high grade hypertension with cabozantinib was substantially higher than other four approved VEGFR-TKIs (sorafenib, sunitinib, vandetanib and pazopanib). Expert commentary: Cancer patients receiving cabozantinib have an increased risk of developing hypertension. Close monitoring and management of hypertension are recommended.

Keywords: Cabozantinib; cancer patients; hypertension; meta-analysis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Anilides / adverse effects*
  • Anilides / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / epidemiology
  • Incidence
  • Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridines / adverse effects*
  • Pyridines / therapeutic use
  • Risk

Substances

  • Anilides
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Pyridines
  • cabozantinib