Charles J. Ryan, MD
An interim analysis of the COU-AA-302 phase III trial investigating the use of abiraterone acetate (Zytiga) in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) showed a trend toward improvement in progression-free survival (PFS) and overall survival (OS), suggesting that the recently approved drug could be safely delivered in an earlier setting. The results were presented at ASCO 2012.
Abiraterone is an androgen synthesis inhibitor, part of a class of newer agents that are designed to target androgen receptors to block the signaling pathways associated with prostate cancer. In April 2011, abiraterone was approved by the FDA to treat patients with mCRPC who had previously received docetaxel. However, studies such as COU-AA-302 are attempting to determine whether the drug can be given prior to chemotherapy.
In the ongoing COU-AA-302 study, 1088 chemotherapy- naïve, asymptomatic or mildly symptomatic patients with mCRPC were randomized 1:1 to receive either 1 g of abiraterone once daily plus 5 mg of prednisone twice daily or placebo plus 5 mg of prednisone twice daily. The primary endpoints are radiographic PFS and OS.
At the time of the interim analysis, 43% of total events had been reported. The median PFS in the control arm was 8.3 months; however, the median PFS could not be determined for the abiraterone group. Based on independent analysis, the median PFS appeared to be approximately doubled in the abiraterone arm (hazard ratio [HR] = 0.43; 95% CI, 0.35-0.52; P
The median OS also could not be determined at the interim analysis. The OS in the control arm was 27.2 months, the longest median OS measured in any phase III mCRPC study. The independent analysis showed that there was an approximate 25% increase in OS in the abiraterone arm (HR = 0.75; 95% CI, 0.61-0.93; P
In March, the study was unblinded so that patients in the control arm could receive abiraterone.
As compared with the placebo group, the abiraterone arm experienced higher rates of grade 3 and 4 adverse events, including hypertension (4.9% vs 3.0%), hypokalemia (2.4% vs 1.9%), elevated ALT levels (5.4% vs 0.8%), and elevated AST levels (3.0% vs 0.9%).
The results of this study suggest that abiraterone might be safe to give to patients earlier in the treatment course than its currently approved indication, according to lead study author Charles J. Ryan, MD, University of California San Francisco Helen Diller Family Comprehensive Cancer Center.
“We have an orally available, well-tolerated, generally safe agent that leads to clinical responses in over half of patients who take it,” Ryan said.
Based on the COU-AA-302 data, Johnson & Johnson submitted a supplemental New Drug Application to the FDA in June seeking to expand abiraterone’s label to include treatment of symptomatic or mildly symptomatic, chemotherapynaïve patients with mCRPC following the failure of androgen deprivation therapy.
Ryan CJ, Smith MR, De Bono JS, et al. Interim analysis (IA) results of COU-AA-302, a randomized, phase III study of abiraterone acetate (AA) in chemotherapy-naïve patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2012;30(suppl; abstr LBA4518).