URO ONCO

Welcome, this website is intended for all international healthcare professionals in uro-oncology. By clicking the link below you are declaring and confirming that you are a healthcare professional.

You are here

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial

Lancet Oncol. 2014 Oct;15(11):1263-8.

Lancet Oncol. 2014 Oct;15(11):1263-8.

Abstract

BACKGROUND:

In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy.

METHODS:

We did a multicentre, open-label, early-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression, development of sustained side-effects, or abiraterone acetate becoming available in the respective country. The primary outcome was the number of adverse events arising during study treatment and within 30 days of discontinuation. Efficacy measures (time to prostate-specific antigen [PSA] progression and time to clinical progression) were gathered to guide treatment decisions. We included in our analysis all patients who received at least one dose of abiraterone acetate. This study is registered with ClinicalTrials.gov, number NCT01217697.

FINDINGS:

Between Nov 17, 2010, and Sept 30, 2013, 2314 patients were enrolled into the early-access protocol trial. Median follow-up was 5·7 months (IQR 3·5-10·6). 952 (41%) patients had a grade 3 or 4 treatment-related adverse event, and grade 3 or 4 serious adverse events were recorded in 585 (25%) people. The most common grade 3 and 4 adverse events were hepatotoxicity (188 [8%]), hypertension (99 [4%]), cardiac disorders (52 [2%]), osteoporosis (31 [1%]), hypokalaemia (28 [1%]), and fluid retention or oedema (23 [1%]). 172 (7%) patients discontinued the study because of adverse events (64 [3%] were drug-related), as assessed by the investigator, and 171 (7%) people died. The funder assessed causes of death, which were due to disease progression (85 [4%]), an unrelated adverse experience (72 [3%]), and unknown reasons (14 [1%]). Of the 86 deaths not attributable to disease progression, 18 (<1%) were caused by a drug-related adverse event, as assessed by the investigator. Median time to PSA progression was 8·5 months (95% CI 8·3-9·7) and median time to clinical progression was 12·7 months (11·8-13·8).

INTERPRETATION:

No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients' outcomes.

FUNDING:

Janssen Research & Development.

Copyright © 2014 Elsevier Ltd. All rights reserved.

Comment from Henk van der Poel:  Early access program that showed similar toxicity of abiraterone as compared to the clinical trial after chemotherapy (COU-AA-301). Interestingly, median time to PSA progression was 8.5m and identical to data from COU-AA-301 that confirms the data in a less stringent population.

E-Alert

Subscribe to our E-Alert to keep up to date with the new items in the Resource Centre

Subscribe

URO ONCO is made possible by an unrestricted educational grant from:

The editorial independence of the resource centre is mandatory and recognized by the EAU and Elsevier.

The journal articles, videos and statements published on the resource centre have been selected independently and without influence from Elsevier, European Urology Editors or the sponsor and do not necessarily reflect their opinions or views.