• Paul G Kluetz, Yang-Min Ning, V Ellen Maher, Lijun Zhang, Shenghui Tang, Debasis Ghosh, Robeena Aziz, Todd Palmby, Elimika Pfuma, Jeanne Fourie Zirkelbach, Nitin Mehrotra, Amy Tilley, Rajeshwari Sridhara, Amna Ibrahim, Robert Justice, and Richard Pazdur.
• 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.
• Clin Cancer Res. 2013 Dec 15;19(24):6650-6.

AbstractOn 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.©2013 AACR.

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