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 journalReview article

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

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Thornton, K., Kim, G., Maher, V. E., Chattopadhyay, S., Tang, S., Moon, Y. J., 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., ... 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, 18(14), 3722-3730. https://doi.org/10.1158/1078-0432.CCR-12-0411