• Oncology Clinical Trials
• Reproductive Cancers

• Oncology Clinical Trials
• Oncology
• Reproductive Cancers

Abiraterone acetate as therapy for chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) improved overall survival (OS) compared with placebo in the final OS analysis of the phase 3 COU-AA-302 clinical trial.

Charles J. Ryan, MD, University of California, San Francisco, San Francisco, California, USA, presented data from more than 4 years of follow-up from the international, randomized, double-blind, placebo-controlled COU-AA-302. Abiraterone is an orally available inhibitor of the CYP17 enzyme complex, a key regulator of androgen synthesis.

Eligible patients for the trial were required to have mCRPC and to be free of disease-related symptoms that would lead to a requirement for opiate analgesic use. The study included 1088 men with mCRPC who were randomized in a 1:1 fashion to receive abiraterone acetate 1000 mg QD with concurrent prednisone 5 mg BID, or placebo plus prednisone 5 mg BID. The co-primary end points were radiographic progression-free survival (rPFS) and OS.

The study was unblinded on the recommendation of the Independent Data Safety Monitoring Committee after the second interim analysis based on a significant difference in rPFS as well as an emerging trend for OS in favor of abiraterone. After unblinding, the study was not discontinued. A subsequent protocol amendment allowed patients in the placebo arm to receive abiraterone. The current analysis incorporated survival and other data after the observation of 741 deaths.

Treatment arms were evenly matched with respect to common clinical and prognostic variables. The median PSA level was approximately 40 ng/mL in both arms. Approximately half of the patients enrolled had 10 or more bone metastases.

Eighty percent of patients in the placebo arm and 67% in the abiraterone arm received subsequent therapy for mCRPC prior to unblinding of the study. The most common subsequent therapy was docetaxel (about 60% in each arm).

Three interim analyses were conducted. As assessed by investigator review, abiraterone doubled the time to rPFS from 8.2 to 16.5 months (HR, 0.52; P < .0001) at the time of the third interim analysis [Rathkopf DE et al. Eur Urol. 2014].

The final analysis consisted of data from a median follow-up of 49.2 months. At this time, 92% of patients in the abiraterone arm and 100% in the placebo arm had discontinued therapy, most often for radiographic progression. Median OS was 34.7 months in the abiraterone arm and 30.3 months in the placebo arm, corresponding to a 19% relative reduction in the risk of death (HR, 0.81; P = .0033). The treatment effect of abiraterone was more pronounced when adjusting for the 44% of patients receiving prednisone who subsequently received abiraterone (HR, 0.74). More than one-fourth of patients randomized into the abiraterone arm have survived for 48 months or longer, noted Dr Ryan.

The final analysis also demonstrated a significant improvement in median time to opiate use for cancer-related pain when comparing abiraterone versus placebo (median, 33.4 vs 23.4 months, respectively; HR, 0.72; P < .00001). With 2 additional years of follow-up since the previous clinical cutoff, the safety profile of abiraterone remained unchanged. No new safety signals emerged despite the longer duration of therapy and follow-up compared with prior analyses.

• © 2014 MD Conference Express®