TY - JOUR
T1 - Safety and efficacy of two starting doses of vandetanib in advanced medullary thyroid cancer
AU - Hu, Mimi I.
AU - Elisei, Rossella
AU - Dedecjus, Marek
AU - Popovtzer, Aron
AU - Druce, Maralyn
AU - Kapiteijn, Ellen
AU - Pacini, Furio
AU - Locati, Laura
AU - Krajewska, Jolanta
AU - Weiss, Richard
AU - Gagel, Robert F.
N1 - Funding Information:
This work was supported by Sanofi and the University of Texas MD Anderson Cancer Center (Cancer Center Support Grant CA16672).
Funding Information:
The authors thank Richard Ogilvy-Stewart from Mudskipper Business Ltd who provided medical writing assistance funded by Sanofi Genzyme.
Publisher Copyright:
© 2019 Society for Endocrinology Published by Bioscientifica Ltd. Printed in Great Britain
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Efficacy
KW - Medullary thyroid cancer
KW - Safety
KW - Vandetanib
UR - http://www.scopus.com/inward/record.url?scp=85058745190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058745190&partnerID=8YFLogxK
U2 - 10.1530/ERC-18-0258
DO - 10.1530/ERC-18-0258
M3 - Article
C2 - 30557850
AN - SCOPUS:85058745190
SN - 1351-0088
VL - 26
SP - 241
EP - 250
JO - Endocrine-related cancer
JF - Endocrine-related cancer
IS - 2
ER -