In December, the FDA approved an expanded indication for abiraterone acetate (Zytiga) in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer.
Trial Design
The approval was based on a trial randomly assigning 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 coprimary endpoints were radiographic progression-free survival and overall survival. Treatment with abiraterone acetate improved radiographic progression-free survival. The median radiographic progression-free survival 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 < .0001]. At the prespecified third interim analysis, median overall survival was 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
Safety data were evaluated in 1,333 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.
The recommended dose and schedule for abiraterone acetate is 1,000 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. ■
