Vandetanib for the Treatment of Symptomatic or Progressive Medullary Thyroid Cancer in Patients with Unresectable Locally Advanced or Metastatic Disease: U.S. Food and Drug Administration Drug Approval Summary
Cet article résume les données ayant servi de base à la Food and Drug Administration pour autoriser, en avril 2011, la mise sur le marché du vandetanib dans le traitement d'un cancer médullaire thyroïdien
On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa Tablets, AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced or metastatic disease. Vandetanib is the first drug approved for this indication and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib 300 mg/day orally (n=231) or to placebo (n=100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared to placebo. Other endpoints included evaluation of overall survival (OS) and objective response rate (ORR). The PFS analysis showed a marked improvement for patients randomized to vandetanib (HR=0.35; 95% CI: 0.24-0.53; p<0.0001). The objective response rate for the vandetanib arm was 44% compared to 1% for the placebo arm. The most common grade 3 and 4 toxicities (>5%) were diarrhea/colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash and corrected Q-T interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in progression-free survival. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the Vandetanib Risk Evaluation Mitigation Strategy (REMS) Program, are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic or slowly progressing disease.