Vandetanib (Zactima) received full approval from the US Food and Drug Administration (FDA) today for adults with nonresectable or metastatic medullary thyroid cancer (MTC). Vandetanib was initially approved under the FDA's orphan drug program, making it the first medical treatment for MTC.
Approval was based on data from the phase 3 ZETA trial (N = 331), which compared vandetanib (n = 231) with placebo (n = 100). Although the study found that vandetanib did not improve overall survival, progression-free survival (PFS) for the patients in this arm was extended by a median of 6.2 months compared with PFS for patients taking placebo, which was significant (22.6 months vs 16.4 months, respectively; P <0001). The difference translates to a 65% reduction in the risk for disease progression.
The drug has been given a boxed warning that notes the risk of treatment-related QT prolongation, Torsades de points, and sudden death in patients taking vandetanib. The FDA also requested that AstraZeneca, which markets the drug, develop a Risk Evaluation and Mitigation Strategy (REMS). To distribute vanadetanib, prescribers and pharmacies will have to receive certification from the vandetanib REMS program. The black box warning notes that vandetanib has a half-life of 19 days, which could delay resolution of adverse reactions.
Patients in the vandetanib arm fo the ZETA trial receoved a 300-mg dose once daily. Treatment-related adverse effects occurring in more than 20% of patients in this group included diarrhea (57%), rash (53%), acne (35%), nausea (33%), hypertension (33%), headache (26%), fatigue (24%), decreased appetite (21%), and abdominal pain.
Vandetanib is an oral inhibitor of epithelial growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR). An Oncologic Drugs Advisory Committee convened in December 2010 recommended conducting additional trials to evaluate the safety and efficacy of using alternative dosing regimens for vandetanib. They suggested that lower drug levels might prove equally effective but cause less toxicity.
Read the press release here:
www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm250168.htm.
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