U.S. Food and Drug Administration Approval: Vismodegib for Recurrent, Locally Advanced or Metastatic Basal Cell Carcinoma
Cet article présente les données ayant servi de base à l'autorisation de mise sur le marché américain du vismodegib pour le traitement de patients ateints d'un carcinome basocellulaire métastatique ou localement avancé
The data and regulatory considerations leading to FDA's January 30, 2012 approval of ErivedgeTM (vismodegib) capsules for the treatment of patients with recurrent, locally advanced or metastatic basal cell carcinoma (BCC) are described. FDA's approval decision was based primarily on the results observed in a single-arm, parallel-cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6, 48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5, 56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.