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 (AA) plus prednisone (N = 546) or placebo plus prednisone (N = 542). The co-primary 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 AA arm (HR 0.43 (95% CI: 0.35, 0.52), p < 0.0001). A pre-specified interim analysis demonstrated an improvement in OS favoring the AA 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 AA. Full approval was granted based on 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 utilize 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 AA for patients with mCRPC who had received prior chemotherapy containing docetaxel.
Written by:
Kluetz PG, Ning YM, Maher VE, Zhang L, Tang S, Ghosh D, Aziz R, Palmby T, Pfuma E, Fourie Zirkelbach J, Mehrotra N, Tilley A, Sridhara R, Ibrahim A, Justice R, Pazdur R. Are you the author?
Office of Hematology and Oncology Products, Food and Drug Administration.
Reference: Clin Cancer Res. 2013 Oct 22. Epub ahead of print.
doi: 10.1158/1078-0432.CCR-13-2134
PubMed Abstract
PMID: 24150234
UroToday.com mCRPC Treatment Section
