Safety and efficacy of two starting doses of vandetanib in advanced medullary thyroid cancer

Mimi I. Hu, Rossella Elisei, Marek Dedecjus, Aron Popovtzer, Maralyn Druce, Ellen Kapiteijn, Furio Pacini, Laura Locati, Jolanta Krajewska, Richard Weiss, Robert F. Gagel

Research output: Contribution to journalArticle

Abstract

Vandetanib is an oral tyrosine kinase inhibitor approved for treatment of advanced symptomatic or progressive medullary thyroid cancer (MTC). The current study (NCT01496313) evaluated the benefit-risk of two starting doses of vandetanib in patients with symptomatic or progressive MTC. Patients were randomized 1:1 to receive vandetanib 150 or 300 mg daily and followed for a maximum of 14 months (Part A), with the option to then enter an open-label phase (Part B) investigating vandetanib 100, 150, 200 and 300 mg daily doses. Efficacy was assessed in Part A, and safety and tolerability during Parts A and B up to 2 years post randomization. Eighty-one patients were randomized in Part A and 61 patients entered Part B, of whom 37 (60.7%) received 2 years of treatment. Overall, 25% of patients experienced an objective response (OR) at 14 months (OR rate, 0.29 (95% CI, 0.176-0.445) for 300 mg, and 0.20 (95% CI, 0.105-0.348) for 150 mg; one-sided P value approximately 0.43). The most common adverse events (AEs) included diarrhea, hypocalcemia, asthenia, QTc prolongation, hypokalemia and keratopathy, all at generally higher incidence with 300 vs 150 mg (Part A). Part B safety and tolerability was consistent with Part A. OR was observed with both vandetanib doses; the 300 mg dose showed a more favorable trend vs 150 mg as initial dose. Thus, for most patients, 300 mg vandetanib is the most appropriate starting dose; dose reductions to manage AEs and lower initial doses for patients with particular comorbidities can be considered.

Original languageEnglish
Pages (from-to)241-250
Number of pages10
JournalEndocrine-Related Cancer
Volume26
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Efficacy
  • Medullary thyroid cancer
  • Safety
  • Vandetanib

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

Fingerprint Dive into the research topics of 'Safety and efficacy of two starting doses of vandetanib in advanced medullary thyroid cancer'. Together they form a unique fingerprint.

  • Cite this

    Hu, M. I., Elisei, R., Dedecjus, M., Popovtzer, A., Druce, M., Kapiteijn, E., Pacini, F., Locati, L., Krajewska, J., Weiss, R., & Gagel, R. F. (2019). Safety and efficacy of two starting doses of vandetanib in advanced medullary thyroid cancer. Endocrine-Related Cancer, 26(2), 241-250. https://doi.org/10.1530/ERC-18-0258