Expanded Approval forAbiraterone Acetate

On December 10, 2012, the U. S. Food and Drug Administration approved an expanded indication for abiraterone acetate (Zytiga Tablets, Janssen Biotech, Inc.) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.

The approval was based on a trial randomizing patients with metastatic castration-resistant prostate cancer who had not received cytotoxic chemotherapy to either abiraterone acetate plus prednisone (N = 546) or placebo plus prednisone (N = 542).  Entry was restricted to patients with metastases to the bone, soft tissue, or lymph nodes. Patients with moderate to severe cancer pain or opiate use for cancer pain were excluded.  All patients had a prior orchiectomy or continued to receive a gonadotropin releasing hormone analog.
The co-primary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS).  Treatment with abiraterone acetate improved rPFS.  The median rPFS was 8.3 months in the placebo arm and had not yet been reached for those receiving abiraterone acetate [HR 0.43 (95% CI: 0.35, 0.52), p < 0.0001]. At the pre-specified third interim analysis, median OS were 35.3 and 30.1 months in the abiraterone acetate and placebo arms, respectively [HR 0.79 (95% CI: 0.66, 0.96)].  These results did not cross the O’Brien-Fleming boundary for statistical significance.  The primary endpoints were supported by statistically significant improvements in time-to-opiate use and time-to-cytotoxic chemotherapy.
Safety data were evaluated in 1333 patients with metastatic castration-resistant prostate cancer who received abiraterone acetate plus prednisone and in 934 patients who received placebo plus prednisone in this and the other pivotal trial.  The most common (≥10%) adverse reactions included fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary tract infection, and contusion.  The most common laboratory abnormalities (> 20%) included anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia, elevated AST, hypophosphatemia, elevated ALT, and hypokalemia.
Grade 3-4 adverse reactions occurred in 55% of patients receiving abiraterone acetate and in 50% receiving placebo.  Grade 3-4 increases in ALT or AST occurred in 4% of patients in the abiraterone acetate arm.  Grade 3-4 cardiac failure occurred more commonly in patients treated with abiraterone acetate compared to those receiving placebo (1.6% vs. 0.2%).  Adrenal insufficiency occurred in 0.5% of patients taking abiraterone acetate and in 0.2% of those receiving placebo.  Patients should be monitored for adrenocortical insufficiency and mineralocorticoid excess.
The recommended dose and schedule for abiraterone acetate is 1000 mg administered orally once daily in combination with prednisone 5 mg administered orally twice daily.  Abiraterone acetate must be taken on an empty stomach.  No food should be consumed for at least 2 hours before and for at least 1 hour after abiraterone acetate.  Abiraterone Cmax and AUC0-∞ (exposure) were increased up to 17- and 10-fold higher, respectively, when a single dose of abiraterone acetate was administered with a meal compared to a fasted state.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Page Last Updated: 02/19/2016
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