The US Food and Drug Administration (FDA) approved the orphan drug vandetanib (trade name pending; AstraZeneca), a tyrosine kinase inhibitor, for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first and only FDA approved treatment for this rare cancer.
“Vandetanib’s approval underscores the FDA’s commitment to approving treatments for patients with rare and difficult-to-treat diseases,” said Richard Pazdur, MD, Director of the Office of Oncology Drug Products at the FDA.
The recommended dose is 300 mg administered orally once daily. For patients with moderate renal impairment or severe impairment, the starting dose should be 200 mg.
Medullary thyroid cancer can occur spontaneously or present as part of a genetic syndrome. Its estimated incidence in the United States in 2010 was 1300 to 2200 cases, representing 3% to 5% of all cases of thyroid cancer.
The approval was based on an international, multicenter, randomized, double-blind trial involving 331 patients with unresectable locally advanced or metastatic medullary thyroid carcinoma.
The median progression-free survival (PFS) rate was 22.6 months with vandetanib versus 16.4 months with placebo. Overall, 15% of the patients had died, and overall survival (OS) did not differ between the 2 groups. The most common grade 3 or 4 adverse events (≥5%) were diarrhea/colitis, hypertension and hypertensive crisis, QT prolongation, fatigue, and rash. Five patients who received vandetanib died from respiratory failure, respiratory arrest, aspiration pneumonia, cardiac failure with arrhythmia, or sepsis; 2 additional patients died after data were collected.
Vandetanib is associated with serious adverse effects and was approved with a risk evaluation and mitigation strategy program. (April 6, 2011)
