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

Katherine Thornton, Geoffrey Kim, V. Ellen Maher, Somesh Chattopadhyay, Shenghui Tang, Young Jin Moon, Pengfei Song, Anshu Marathe, Suchitra Balakrishnan, Hao Zhu, Christine Garnett, Qi Liu, Brian Booth, Brenda Gehrke, Robert Dorsam, Leigh Verbois, Debasis Ghosh, Wendy Wilson, John Duan, Haripada SarkerSarah Pope Miksinski, Lisa Skarupa, Amna Ibrahim, Robert Justice, Anthony Murgo, Richard Pazdur

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3722-3730
Number of pages9
JournalClinical Cancer Research
Volume18
Issue number14
DOIs
StatePublished - Jul 15 2012
Externally publishedYes

Fingerprint

Drug Approval
Disease-Free Survival
Therapeutics
Placebos
Medullary Thyroid cancer
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Hypocalcemia
Pharmacies
United States Food and Drug Administration
Colitis
Survival Analysis
Sudden Death
Exanthema
Pharmaceutical Preparations
Tablets
Fatigue
Diarrhea
Confidence Intervals
Hypertension

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Thornton, Katherine; Kim, Geoffrey; Maher, V. Ellen; Chattopadhyay, Somesh; Tang, Shenghui; Moon, Young Jin; Song, Pengfei; Marathe, Anshu; Balakrishnan, Suchitra; Zhu, Hao; Garnett, Christine; Liu, Qi; Booth, Brian; Gehrke, Brenda; Dorsam, Robert; Verbois, Leigh; Ghosh, Debasis; Wilson, Wendy; Duan, John; Sarker, Haripada; Miksinski, Sarah Pope; Skarupa, Lisa; Ibrahim, Amna; Justice, Robert; Murgo, Anthony; Pazdur, Richard.

In: Clinical Cancer Research, Vol. 18, No. 14, 15.07.2012, p. 3722-3730.

Research output: Contribution to journalArticle

Thornton, K, Kim, G, Maher, VE, Chattopadhyay, S, Tang, S, Moon, YJ, Song, P, Marathe, A, Balakrishnan, S, Zhu, H, Garnett, C, Liu, Q, Booth, B, Gehrke, B, Dorsam, R, Verbois, L, Ghosh, D, Wilson, W, Duan, J, Sarker, H, Miksinski, SP, Skarupa, L, Ibrahim, A, Justice, R, Murgo, A & Pazdur, R 2012, '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', Clinical Cancer Research, vol. 18, no. 14, pp. 3722-3730. https://doi.org/10.1158/1078-0432.CCR-12-0411
Thornton, Katherine ; Kim, Geoffrey ; Maher, V. Ellen ; Chattopadhyay, Somesh ; Tang, Shenghui ; Moon, Young Jin ; Song, Pengfei ; Marathe, Anshu ; Balakrishnan, Suchitra ; Zhu, Hao ; Garnett, Christine ; Liu, Qi ; Booth, Brian ; Gehrke, Brenda ; Dorsam, Robert ; Verbois, Leigh ; Ghosh, Debasis ; Wilson, Wendy ; Duan, John ; Sarker, Haripada ; Miksinski, Sarah Pope ; Skarupa, Lisa ; Ibrahim, Amna ; Justice, Robert ; Murgo, Anthony ; Pazdur, Richard. / 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. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 14. pp. 3722-3730.
@article{0cf2af9759634f298f8f386e93910898,
title = "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",
abstract = "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.",
author = "Katherine Thornton and Geoffrey Kim and Maher, {V. Ellen} and Somesh Chattopadhyay and Shenghui Tang and Moon, {Young Jin} and Pengfei Song and Anshu Marathe and Suchitra Balakrishnan and Hao Zhu and Christine Garnett and Qi Liu and Brian Booth and Brenda Gehrke and Robert Dorsam and Leigh Verbois and Debasis Ghosh and Wendy Wilson and John Duan and Haripada Sarker and Miksinski, {Sarah Pope} and Lisa Skarupa and Amna Ibrahim and Robert Justice and Anthony Murgo and Richard Pazdur",
year = "2012",
month = "7",
day = "15",
doi = "10.1158/1078-0432.CCR-12-0411",
language = "English (US)",
volume = "18",
pages = "3722--3730",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "14",

}

TY - JOUR

T1 - Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease

T2 - U.S. Food and Drug Administration Drug approval summary

AU - Thornton, Katherine

AU - Kim, Geoffrey

AU - Maher, V. Ellen

AU - Chattopadhyay, Somesh

AU - Tang, Shenghui

AU - Moon, Young Jin

AU - Song, Pengfei

AU - Marathe, Anshu

AU - Balakrishnan, Suchitra

AU - Zhu, Hao

AU - Garnett, Christine

AU - Liu, Qi

AU - Booth, Brian

AU - Gehrke, Brenda

AU - Dorsam, Robert

AU - Verbois, Leigh

AU - Ghosh, Debasis

AU - Wilson, Wendy

AU - Duan, John

AU - Sarker, Haripada

AU - Miksinski, Sarah Pope

AU - Skarupa, Lisa

AU - Ibrahim, Amna

AU - Justice, Robert

AU - Murgo, Anthony

AU - Pazdur, Richard

PY - 2012/7/15

Y1 - 2012/7/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863890768&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863890768&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-12-0411

DO - 10.1158/1078-0432.CCR-12-0411

M3 - Article

C2 - 22665903

AN - SCOPUS:84863890768

VL - 18

SP - 3722

EP - 3730

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 14

ER -