ZETA
ZETA showed that vandetanib, a pill blocking the RET protein that drives most medullary thyroid cancers along with the tumour blood supply, kept advanced disease from growing for much longer than placebo, and it became the first drug ever approved for this rare cancer.
Overview
ZETA was a double-blind placebo-controlled phase 3 trial in patients with unresectable locally advanced or metastatic medullary thyroid cancer, both hereditary and sporadic. Patients were randomised two to one to vandetanib, an oral inhibitor of RET, VEGF receptor and EGFR signalling, or to placebo, with open-label vandetanib offered at progression.
Vandetanib significantly prolonged progression-free survival, the primary endpoint, and improved response and biochemical markers; overall survival was not different, in part because of crossover. Approval in the United States in April 2011 made vandetanib the first drug for advanced medullary thyroid cancer, followed by cabozantinib after EXAM in 2012 and the selective RET inhibitors selpercatinib and pralsetinib in 2020. QT prolongation limits its use.
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