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Clinical Trial
. 2012 Jan 10;30(2):134-41.
doi: 10.1200/JCO.2011.35.5040. Epub 2011 Oct 24.

Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial

Samuel A Wells Jr  1 , Bruce G Robinson, Robert F Gagel, Henning Dralle, James A Fagin, Massimo Santoro, Eric Baudin, Rossella Elisei, Barbara Jarzab, James R Vasselli, Jessica Read, Peter Langmuir, Anderson J Ryan, Martin J Schlumberger
Affiliations
Clinical Trial

Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial

Samuel A Wells Jr et al. J Clin Oncol. .

Erratum in

  • J Clin Oncol. 2013 Aug 20;31(24):3049

Abstract

Purpose: There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC.

Patients and methods: Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments.

Results: Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%).

Conclusion: Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram.
Fig 2.
Fig 2.
(A) Kaplan-Meier curve of progression-free survival (PFS; intention-to-treat population; all randomly assigned patients); derived from all available centralized Response Evaluation Criteria in Solid Tumors (RECIST) assessments. (B) Forest plot of hazard ratios for PFS according to baseline characteristics and disease status. (C) Forest plot of hazard ratios for PFS according to rearranged during transfection (RET) mutation status and M918T mutation status in patients with sporadic medullary thyroid carcinoma. (B, C) A hazard ratio < 1 favors vandetanib. The analyses were performed using a log-rank test with treatment as the only factor.
Fig 3.
Fig 3.
Kaplan-Meier curve of overall survival (intention-to-treat population; all randomly assigned patients).
Fig A1.
Fig A1.
Kaplan-Meier curve of time to worsening of pain (intention-to-treat population; all randomly assigned patients).
See this image and copyright information in PMC

Comment in

References

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