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

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.