The FINANCIAL — AstraZeneca announced on June 7 results from ZETA, a phase III study in patients with advanced medullary thyroid cancer (MTC), showed that treatment with the investigational drug vandetanib significantly extended Progression Free Survival (PFS), the primary endpoint of the study, by demonstrating a 54% reduction in the rate of progression compared to placebo (HR=0.46, p=0.0001).
The results of the ZETA study were presented today at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
"ZETA was a phase III, randomized, double-blind, placebo-controlled, multi-center study, evaluating oral once-daily vandetanib 300mg in 331 patients with unresectable, locally advanced or metastatic hereditary or sporadic medullary thyroid cancer and the presence of a measurable tumor. This was the first phase III trial with definitive results, carried out for patients with advanced MTC," AstraZeneca informs.
Significant differences for vandetanib compared to placebo were also observed in secondary endpoints of objective response rate and disease control rate–the response rate in patients receiving vandetanib was 45%. Patients receiving vandetanib also had a significant decrease in calcitonin and CEA biomarkers. Overall survival (OS) data at the time of presentation was immature.
The most common adverse events associated with vandetanib in this study, included rash, diarrhea, hypertension, fatigue and headache (incidence >20% overall). The incidence of protocol-defined QTc prolongation was 8%. The safety profile of vandetanib in this study was similar to what has been previously observed in other studies in medullary thyroid and non small cell lung cancer.
“Patients with advanced medullary thyroid cancer currently have few or no options for treatment once they reach this late stage of their disease”, said Peter Langmuir, M.D. Executive Director, Medical-Science, AstraZeneca. “Given the results of this trial, we are moving quickly to file regulatory submissions for approval with the FDA and the EMA.”
Vandetanib 300mg has orphan drug designation in the US and Europe for the treatment of patients with advanced medullary thyroid cancer and AstraZeneca plans regulatory submissions in 2010. Vandetanib is thought to work by inhibition of the vascular endothelial growth factor (VEGF) pathway, epidermal growth factor receptor (EGFR) and rearranged during transfection (RET) pathways.