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01.08.2014 | Adis Drug Evaluation
Cabozantinib: A Review of Its Use in Patients with Medullary Thyroid Cancer
Erschienen in: Drugs | Ausgabe 12/2014
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Cabozantinib (Cometriq®) is an orally administered small molecule inhibitor of multiple tyrosine kinase receptors, including those involved in the pathogenesis of medullary thyroid cancer (MTC) [i.e. rearranged during transfection (RET), MET and vascular endothelial growth factor receptor (VEGFR)-2]. Cabozantinib is indicated for the treatment of adults with progressive, unresectable locally advanced (in the EU) or metastatic (in the EU and USA) MTC. Compared with placebo, cabozantinib significantly prolonged progression-free survival, reflecting a 72 % reduction in the risk of disease progression or death, in patients with unresectable, locally advanced or metastatic MTC participating in a multinational, phase III study. A significantly higher proportion of patients receiving cabozantinib than those receiving placebo achieved an objective response or disease stabilization (i.e. a complete or partial response, or stable disease). The overall survival benefit with cabozantinib is as yet unclear, with no significant benefit observed in two interim analyses (one prespecified, and one unplanned and conducted at the request of the US FDA). The tolerability profile of oral cabozantinib is typical for a small molecule targeting the VEGFR and other tyrosine kinase-mediated pathways, with adverse events associated with the inhibition of the VEGF pathway (e.g. gastrointestinal perforation, haemorrhage, hypertension and venous thrombosis) reported in the phase III study. Treatment-emergent adverse events were generally managed with supportive therapy, dose reductions and/or dose interruptions. Although final overall survival data are awaited, current evidence suggests cabozantinib to be a valuable treatment option for adults with progressive, unresectable locally advanced or metastatic MTC.