NDA20-498S012CASODEX(bicalutamide)150mg.pptVIP

NDA 20-498 / S012CASODEX (bicalutamide) 150 mg FDA Review Division of Reproductive and Urologic Drug Products (DRUDP) Outline of FDA Presentation Background and Review Issues Dan Shames, M.D., Director, DRUDP Review of Clinical Trial Data Scott Monroe, M.D., Medical Team Leader, DRUDP Summary of Review Issues and Introduction of Questions Dan Shames, M.D. Background Importance of current supplement on the public health Importance of adequate staging in the treatment of prostate cancer History of Casodex 150mg development Public Health Importance Would be first approved drug for non-metastatic prostate cancer Target population of hundreds of thousands Therapy not warranted in a proportion of patients Variable natural history of prostate cancer Side effects possible without drug benefit Drug could be used for years or decades Prediction of Prognoses of Prostate Cancer Subpopulations Definition of Prostate Cancer Subpopulation Clinical/path stage Gleason Score measure of differentiation Gleason score assigned by improper methodology in non US studies PSA Partin, D’Amico, etc. Gleason adds to precision of staging and prognosis History of CASODEX 150 Trials 306 307 Randomized, parallel studies in “Advanced” carcinoma of prostate (1992) M0 = T3/T4 , PSA = 5 x ULN (N=490) M1 = bone mets (N=960) Casodex 150 vs. castration (medical or surgical) Intent of study to show survival non-inferiority of Casodex compared to castration to show QOL advantage of Casodex compared to castration Trials 306 307 DSMB stopped the trials for M1 patients Casodex compared to castration decreased survival increased progression in both trials Trials continued with M0 patients only Trial 306 (N=128) Trial 307 (N=352) Trials 306 307 (NDA 20-498 / S006) Submitted 2/25/00 “To compare in a combined analysis, the selected dose of Casodex 150mg with medical or surgical castration in terms of survival, time to progression and time to treatment failure, QOL and tolerability in pati