Abiraterone plus prednisone reduces the risk of disease progression and delays the time to opiate use and chemotherapy versus prednisone alone in men with metastatic castration-resistant prostate cancer (mCRPC) who had not received chemotherapy for metastatic disease, according to a long-term analysis of the COU-AA-302 trial presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting. Treatment with abiraterone plus prednisone was safe, and no new safety concerns emerged with longer follow-up.
Abiraterone plus prednisone received expanded approval from the US Food and Drug Administration in December 2012 for men with chemotherapy-naive mCRPC, based on updated interim results of COU-AA-302.
“Building on an increased understanding of the continued relevance of the androgen signaling pathway in CRPC, abiraterone impairs androgen synthesis by selective inhibition of the CYP17 enzyme complex and is now approved for the treatment of mCRPC across the spectrum of disease states,” said lead author Dana Rathkopf, MD, of Memorial Sloan-Kettering Cancer Center in New York City. Rathkopf presented updated safety and efficacy results from COU-AA-302 at ASCO.
The study evaluated 1082 men with asymptomatic or mildly symptomatic progressive mCRPC not treated with prior chemotherapy. They were randomized to receive abiraterone plus prednisone versus prednisone alone.
The phase 3 multinational, randomized, double-blind, placebo-controlled study was conducted at 151 sites in 12 countries, enrolling patients from April 2009 to June 2010. Median duration of follow-up was 27.1 months.
An interim analysis showed that abiraterone plus prednisone significantly improved radiographic progression-free survival (rPFS; P <.0001). A nonsignificant trend was seen for improved overall survival (OS) with abiraterone treatment.
Results of the longer-term analysis were similar to those reported at the interim analysis. Abiraterone significantly improved rPFS versus prednisone alone, reducing the risk of disease progression by 48%: median of 16.5 months versus 8.2 months, respectively (P <.0001). OS was a median of 35.3 months in the abiraterone-treated group versus 30.1 months in the prednisone-alone group (not significant).
Significant differences favoring abiraterone plus prednisone were observed for time to opiate use (P = .0002), time to chemotherapy initiation (P <.0001), time to deterioration in ECOG Performance Status (P = .0052), and time to prostate-specific antigen (PSA) progression (P <.0001).
The percentage of grades 3 and 4 adverse events was low, despite more than 2 years of exposure to abir-aterone. The cumulative incidence of all grades of adverse events was similar across both treatment groups. Rates of infection were high in both treatment groups; the majority of grades 1 and 2 infections were of the upper respiratory tract and upper urinary tract.
Rathkopf DE, Smith MR, De Bono JS, et al. Long-term safety and efficacy analysis of abiraterone acetate (AA) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy (COU-AA-302). J Clin Oncol. 2013;31(suppl):Abstract 5009. Presented at: 2013 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2013; Chicago, IL.