An updated interim analysis of the COU-AA-302 trial upholds the benefits of abiraterone acetate in mildly symptomatic or asymptomatic patients with progressive mCRPC untreated with prior chemotherapy.
Photo Courtesy © ASCO/Todd Buchanan 2013
Dana E. Rathkopf, MD
An updated interim analysis of the COU-AA-302 trial upholds the benefits of abiraterone acetate (Zytiga) in mildly symptomatic or asymptomatic patients with progressive metastatic castration resistant prostate cancer (mCRPC) untreated with prior chemotherapy. At a median follow-up of 27.1 months, radiographic progression-free survival (rPFS) and all secondary endpoints favored the abiraterone acetate arm.
The first interim analysis of COU-AA-302 was presented at the 2012 Annual Meeting of ASCO, and at that time, with a median follow-up of 22 months, results were so favorable for abiraterone acetate that an Independent Data Monitoring Committee recommended unblinding the study and offering all patients abiraterone acetate. COU-AA-302 was the first randomized controlled trial to show benefits for both overall survival (OS) and rPFS in mCRPC.
“The updated analysis resulted in expanded approval of abiraterone in untreated patients with metastatic CRPC and has expanded the way we treat this disease,” said lead author Dana E. Rathkopf, MD, an assistant attending physician in the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center in New York. “Abiraterone can be given pre-chemotherapy and is now approved across the spectrum of metastatic CRPC.”
Abiraterone acetate is a specific inhibitor of CYP17 that blocks androgen biosynthesis and improves OS in mCRPC after treatment with docetaxel. The updated interim analysis presented at the 2013 Genitourinary Cancers Symposium, was prespecified, after 55% of the total OS events occurred. The present analysis confirms the benefits of abiraterone acetate in men with mCRPC who had not received prior chemotherapy.
The international COU-AA-302 tail was conducted at 150 sites around the world. Patients were randomized to receive oral abiraterone acetate 1000 mg plus oral prednisone 5 mg twice daily versus a placebo and prednisone. The co-primary endpoints were rPFS and OS.
At a median follow-up of 27.1 months, OS remained significantly superior with abiraterone acetate, with a median OS of 35.3 months in the experimental arm compared with 30.1 months in the control arm (hazard ratio [HR] = 0.79; 95% CI, 0.66 — 0.96; P < .0151). Abiraterone acetate (AA) was significantly superior to prednisone alone for the following endpoints: rPFS (median of 16.5 months for AA versus 8.3 months for prednisone [HR = 0.53; 95% CI, 0.45 — 0.62; P < .0001]); time to opiate use for cancer pain (not reached for AA versus median of 23.7 months [HR = 0.71; 95% CI, 0.59 — 0.85; P = .0002]); time to initiation of chemotherapy (median of 26.5 months for AA versus 16.8 months for prednisone [HR = 0.61; 95% CI, 0.51 — 0.72; P < .0001]); time to deterioration in ECOG performance status (12.3 months versus 10.9 months, respectively [HR = 0.83; 95% CI, 0.72 — 0.94; P = .0052]); and median time to PSA progression (11.1 months for AA versus 5.6 months for prednisone [HR = 0.50; 95% CI, 0.43 — 0.58; P < .0001]).
Selected adverse events of interest included fatigue, fluid retention, low-grade hypertension, and low-grade hypokalemia. No new safety signals were reported for abiraterone acetate or prednisone beyond 2 years in this analysis.
“Treatment with abiraterone reduced the risk of disease progression by 47%, and decreased the risk of death by 21%,” Rathkopf said. “The updated analysis showed that the drug is safe and well tolerated with longer exposure.”
Rathkopf DE, Smith MR, De Bono JS, et al. Updated interim analysis (IA) of COU-AA-302, a randomized phase III study of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy. J Clin Oncol. 2013;31(suppl 6, abstr 5).