Vandetanib in patients with locally advanced or metastatic medullary thyroid
cancer: a randomized, double-blind phase III trial.
Author(s): Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E,
Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ.
Affiliation(s): Medical Oncology Branch, National Cancer Institute, National Institutes of
Health, Building 10, Room 13N-240E MSC 1206, 9000 Rockville Pike, Bethesda, MD
20892, USA. wellss@mail.nih.gov
Publication date & source: 2012, J Clin Oncol. , 30(2):134-41
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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