Vandetanib is a protein tyrosine kinase inhibitor that has activity against the rearranged during transfection (RET) proto-oncogene. It also acts on both vascular and epidermal growth factor receptors, resulting in reduced endothelial cell migration, proliferation and survival, and reduced blood vessel formation in in vitro models of angiogenesis. Inhibition of angiogenesis has also been observed in mice and in MTC xenograph tumours in vivo; however, the precise mechanism of action in locally advanced or metastatic MTC is unknown.1
In a double-blind study (n=331), patients with advanced MTC were randomised to receive vandetanib (300mg daily) or placebo until disease progression, determined at regular intervals by central independent assessment using the Response Evaluation Criteria in Solid Tumours (RECIST). In the event of disease progression, patients had the option to receive open-label vandetanib.2
Overall, vandetanib significantly prolonged progression-free survival to a greater extent than placebo, with an average duration in the treatment arm of 30.5 months compared with 19.3 months in the control arm (hazard ratio 0.46; 95% CI, 0.31 to 0.69; p=0.0001).2
Adverse events were reported more frequently in patients who received vandetanib than in those who received placebo, with diarrhoea, rash, nausea, hypertension and headache occurring most commonly.1,2
1. Caprelsa Summary of Product Characteristics, February 2012.
2. Wells SA Jr et al. J Clin Oncol 2012; 10; 30: 134-41.
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