A phase III trial among patients with locally advanced or metastatic medullary thyroid cancer met its primary objective of progression-free survival prolongation among patients receiving vandetanib compared to placebo. The secondary efficacy endpoints of objective response rate, disease control rate, and biochemical response “also showed statistically significant benefit in the treatment group compared with the control group,” the investigators reported in the Journal of Clinical Oncology.
Patients were recruited from 23 countries and randomly assigned on a 2:1 basis to vandetanib at 300 mg/d (231) or placebo (100). The mean age was 52 years. Most patients in both groups had sporadic medullary thyroid cancer and metastatic disease. Vandetanib—a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling—had previously shown antitumor activity in a phase II study among patients with the hereditary type of medullary thyroid cancer. Patients with objective disease progression could elect to receive open-label vandetanib.
At a median follow-up of 24 months, 37% of patients had shown disease progression and 15% had died. A final survival analysis is to take place when 50% of the patients have died. Median progression-free survival was 19.3 months in the placebo group, and although median progression-free survival was not yet reached in the vandetanib group, it was estimated at 30.5 months, an estimated prolongation of 11.2 months. “In this clinical study, vandetanib has shown efficacy in patients with locally advanced or metastatic [medullary thyroid cancer], a challenging group of patients for whom there has been no effective therapy,” the authors concluded.
“Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% vs 26%), rash (45% vs 11%), nausea (33% vs 16%), hypertension (32% vs 5%), and headache (26% vs 9%),” the investigators reported. ■
Wells SA, et al: J Clin Oncol 30:134-141, 2012.