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

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).

• Authors: Samuel A Wells Jr, 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 2 Pg. 134-41 (Jan 10 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 22025146 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Piperidines
• Placebos
• Quinazolines
• vandetanib

Topics

• Carcinoma, Neuroendocrine
• Disease Progression
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Piperidines (adverse effects, therapeutic use)
• Placebos
• Quinazolines (adverse effects, therapeutic use)
• Thyroid Neoplasms (drug therapy, pathology)