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Updated phase III clinical trial results provide further evidence that oral abiraterone acetate (ZYTIGA), which was recently approved by the FDA, is well tolerated and has significant clinical benefit in men failing previous intervention for metastatic castration-resistant prostate cancer.
Washington-Updated phase III clinical trial results provide further evidence that oral abiraterone acetate (ZYTIGA), which was recently approved by the FDA, is well tolerated and has significant clinical benefit in men failing previous intervention for metastatic castration-resistant prostate cancer, according to a recent multicenter study presented at the AUA annual meeting in Washington.
First author Fred Saad, MD, spoke on behalf of the investigators for COU-AA-301, a randomized, double-blind, placebo-controlled trial enrolling 1,195 patients at 147 centers in 13 countries. Eligible patients had to show disease progression after docetaxel (Taxotere)-based treatment and no more than one other prior cytotoxic chemotherapeutic regimen, and they were randomized 2:1 to receive abiraterone acetate, 1,000 mg, plus prednisone, 5 mg daily, or placebo plus prednisone, 5 mg.
Statistically significant results confirmed
Compared with the controls, men treated with abiraterone had a 42% longer TTPP (10.2 vs. 6.6 months) and 33% longer rPFS (5.6 vs. 3.6 months). Among men with measurable disease, abiraterone treatment increased the rate of objective response 5.1-fold (14% vs. 2.8%), and the differences favoring abiraterone for all of these endpoints were highly statistically significant, reported Dr. Saad, professor and chief of urology at the University of Montreal Hospital Center.
"These are extraordinary efficacy outcomes that in my opinion are not only statistically significant but also clinically significant and almost unheard of in men with such advanced disease," Dr. Saad said. "The safety data in this group of heavily pretreated men is also very positive.
"Given the limited treatment options available for men with castration-resistant prostate cancer, especially in those who have failed docetaxel, regulatory agency approval of abiraterone acetate should give urologists and patients with prostate cancer something to celebrate."
However, rates of grade 3/4 mineralocorticoid-related adverse events ranged only from 1.3% to 3.8% and were only 1% to 3% higher than in the controls.
"The majority of mineralocorticoid-related adverse events were managed with minimal intervention, such as potassium supplementation or abiraterone dose reduction," Dr. Saad said.
Possible increased cardiac risk?
He added that abiraterone was also associated with a higher rate of grade 3/4 cardiac disorders compared with placebo (4.1% vs. 2.3%), which may also be related to its mineralocorticoid effects.
"However, there was no increase in cardiac-related mortality in the treated arm, and it is not yet clear if there is a true increased risk of cardiac events associated with abiraterone," Dr. Saad told Urology Times.
The overall rate of grade 3/4 adverse events was 55% for the abiraterone group and 58% for the controls. Among grade 3/4 adverse events occurring at a rate higher than 5% in either group, only elevated alkaline phosphatase was more frequent in the abiraterone group than among the controls (18% vs. 13%).
Dr. Saad is an adviser to and has conducted research for Johnson & Johnson.