This early-access protocol trial was initiated after completion of the COU-AA-301 study, which had reported abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy.
An accompanying commentary notes that implementation of an early-access protocol trial and subsequent comparison of data with those from the registration study is challenging, with inherent limitations, as it does not have the strict regimentation and structure of COU-AA-301, and assessments were clinically based. Only serious adverse events as judged by the investigator were recorded, and response assessment was confounded because PSA testing was only required at 3-month intervals, and follow-up imaging was done at the discretion of the treating clinician. In addition, the median duration of abiraterone treatment was shorter in the early-access protocol trial than in COU-AA-301 (4.9 months vs 7.4 months). These differences between studies raise concerns about underestimation of adverse events in the early-access protocol trial. Nevertheless, the commentary is reassured by the absence of any major toxic effects and clear clinical activity. It is anticipated that in practice, abiraterone will probably be used much earlier in the clinical course than in the population evaluated in these studies, and although these findings increase confidence with respect to the safety of abiraterone, the burden is now on individual practitioners to report unusual toxic effects.