title: Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary.
abstract: On December 10, 2012, the U.S. Food and Drug Administration granted full approval for a modified indication for abiraterone acetate (Zytiga tablets; Janssen Biotech, Inc.) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). The approval was based on clinical trial COU-AA-302, which randomly allocated asymptomatic or mildly symptomatic patients with chemotherapy-naïve mCRPC and no visceral metastases to either abiraterone acetate plus prednisone (N = 546) or placebo plus prednisone (N = 542). The coprimary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). The median rPFS was 8.3 months in the placebo arm and had not yet been reached in the abiraterone acetate arm {HR, 0.43 [95% confidence interval (CI) 0.35-0.52]; P < 0.0001}. A prespecified interim analysis demonstrated an improvement in OS favoring the abiraterone acetate arm [HR, 0.79 (95% CI, 0.66-0.96)] but did not cross the O'Brien-Fleming boundary for statistical significance. Safety data confirmed the known adverse reaction profile of abiraterone acetate. Full approval was granted on the basis of a large magnitude of effect on rPFS, a favorable trend in OS, and internal consistency across multiple secondary endpoints and exploratory patient-reported pain data. This is the first drug approval for mCRPC to use rPFS as the primary endpoint. Importantly, this approval was granted in the context of a prior statistically significant OS benefit that formed the basis of the original April 28, 2011, approval of abiraterone acetate for patients with mCRPC who had received prior chemotherapy containing docetaxel.
authors.affiliation: Authors' Affiliations: Office of Hematology and Oncology Products, Office of New Drugs, Office of Biostatistics, Office of Clinical Pharmacology, and Office of New Drug Quality Assessment, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Kluetz
authors.forename: Yang-Min
authors.initials: YM
authors.lastname: Ning
authors.forename: V Ellen
authors.initials: VE
authors.lastname: Maher
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Shenghui
authors.initials: S
authors.lastname: Tang
authors.forename: Debasis
authors.initials: D
authors.lastname: Ghosh
authors.forename: Robeena
authors.initials: R
authors.lastname: Aziz
authors.forename: Todd
authors.initials: T
authors.lastname: Palmby
authors.forename: Elimika
authors.initials: E
authors.lastname: Pfuma
authors.forename: Jeanne Fourie
authors.initials: JF
authors.lastname: Zirkelbach
authors.forename: Nitin
authors.initials: N
authors.lastname: Mehrotra
authors.forename: Amy
authors.initials: A
authors.lastname: Tilley
authors.forename: Rajeshwari
authors.initials: R
authors.lastname: Sridhara
authors.forename: Amna
authors.initials: A
authors.lastname: Ibrahim
authors.forename: Robert
authors.initials: R
authors.lastname: Justice
authors.forename: Richard
authors.initials: R
authors.lastname: Pazdur
mesh_terms: D000069501:Abiraterone Acetate; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D017277:Drug Approval; D006801:Humans; D008297:Male; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000730:Androstadienes; D043823:Taxoids; D000077143:Docetaxel; D000069501:Abiraterone Acetate; D011241:Prednisone