Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary.
On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa tablets; AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first drug approved for this indication, and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other endpoints included evaluation of overall survival and objective response rate. The PFS analysis showed a marked improvement for patients randomized to vandetanib (hazard ratio = 0.35; 95% confidence interval, 0.24-0.53; P < 0.0001). The objective response rate for the vandetanib arm was 44% compared with 1% for the placebo arm. The most common grade 3 and 4 toxicities (>5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in PFS. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease.
Office of Hematology and Oncology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, White Oak, MD, USA.
Katherine
K
Thornton
Geoffrey
G
Kim
V Ellen
VE
Maher
Somesh
S
Chattopadhyay
Shenghui
S
Tang
Young Jin
YJ
Moon
Pengfei
P
Song
Anshu
A
Marathe
Suchitra
S
Balakrishnan
Hao
H
Zhu
Christine
C
Garnett
Qi
Q
Liu
Brian
B
Booth
Brenda
B
Gehrke
Robert
R
Dorsam
Leigh
L
Verbois
Debasis
D
Ghosh
Wendy
W
Wilson
John
J
Duan
Haripada
H
Sarker
Sarah Pope
SP
Miksinski
Lisa
L
Skarupa
Amna
A
Ibrahim
Robert
R
Justice
Anthony
A
Murgo
Richard
R
Pazdur
D018278:Carcinoma, Neuroendocrine; D018572:Disease-Free Survival; D017277:Drug Approval; D006801:Humans; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D014481:United States; D014486:United States Food and Drug Administration
D010880:Piperidines; D011799:Quinazolines; C452423:vandetanib