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Eur Urol. 2014 Nov;66(5):815-25. doi: 10.1016/j.eururo.2014.02.056. Epub 2014 Mar 6.

Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302).

Author information

1
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. Electronic address: rathkopd@mskcc.org.
2
Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
3
The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, Surrey, UK.
4
MD Anderson Cancer Center, Houston, TX, USA.
5
Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA.
6
University of Western Sydney School of Medicine, Penrith, Australia.
7
Institut Gustave Roussy, University of Paris Sud, Villejuif, France.
8
Radboud University Medical Centre, Nijmegen, The Netherlands.
9
Hematology & Oncology Clinics of Australia, Brisbane, Australia.
10
Sarah Cannon Research Institute, Nashville, TN, USA.
11
Oregon Health & Science University Knight Cancer Institute, Portland, OR, USA.
12
Cross Cancer Institute, Edmonton, Alberta, Canada.
13
Laval University, Québec City, Québec, Canada.
14
University Hospital Leuven, Leuven, Belgium.
15
Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
16
University of Colorado Cancer Center and University of Colorado School of Medicine, Aurora, CO, USA.
17
University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
18
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
19
Janssen Research & Development, Los Angeles, CA, USA.
20
Janssen Research & Development, Raritan, NJ, USA.
21
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
22
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA.
23
Janssen Research & Development, Menlo Park, CA, USA.
24
CRCHUM, University of Montréal, Montréal, Québec, Canada.

Abstract

BACKGROUND:

Abiraterone acetate (an androgen biosynthesis inhibitor) plus prednisone is approved for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Study COU-AA-302 evaluated abiraterone acetate plus prednisone versus prednisone alone in mildly symptomatic or asymptomatic patients with progressive mCRPC without prior chemotherapy.

OBJECTIVE:

Report the prespecified third interim analysis (IA) of efficacy and safety outcomes in study COU-AA-302.

DESIGN, SETTING, AND PARTICIPANTS:

Study COU-AA-302, a double-blind placebo-controlled study, enrolled patients with mCRPC from April 2009 to June 2010. A total of 1088 patients were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1).

INTERVENTION:

Patients were randomised 1:1 to abiraterone 1000mg plus prednisone 5mg twice daily by mouth versus prednisone.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Co-primary end points were radiographic progression-free survival (rPFS) and overall survival (OS). Median times to event outcomes were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived using the Cox model, and treatment comparison used the log-rank test. The O'Brien-Fleming Lan-DeMets α-spending function was used for OS. Adverse events were summarised descriptively.

RESULTS AND LIMITATIONS:

With a median follow-up duration of 27.1 mo, improvement in rPFS was statistically significant with abiraterone treatment versus prednisone (median: 16.5 vs 8.2 mo; HR: 0.52 [95% CI, 0.45-0.61]; p<0.0001). Abiraterone improved OS (median: 35.3 vs 30.1 mo; HR: 0.79 [95% CI, 0.66-0.95]; p=0.0151) but did not reach the prespecified statistical efficacy boundary (α-level: 0.0035). A post hoc multivariate analysis for OS using known prognostic factors supported the primary results (HR: 0.74 [95% CI, 0.61-0.89]; p=0.0017), and all clinically relevant secondary end points and patient-reported outcomes improved. While the post hoc nature of the long-term safety analysis is a limitation, the safety profile with longer treatment exposure was consistent with prior reports.

CONCLUSIONS:

The updated IA of study COU-AA-302 in patients with mCRPC without prior chemotherapy confirms that abiraterone delays disease progression, pain, and functional deterioration and has clinical benefit with a favourable safety profile, including in patients treated for ≥24 mo.

TRIAL REGISTRATION:

Study COU-AA-302, ClinicalTrials.gov number, NCT00887198.

PATIENT SUMMARY:

The updated results of this ongoing study showed that disease progression was delayed in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone, and there was a continued trend in prolongation of life compared with patients treated with prednisone alone. Treatment with abiraterone acetate and prednisone was well tolerated by patients who were treated for >2 yr.

KEYWORDS:

Abiraterone acetate; Chemotherapy-naive; Efficacy; Metastatic castration-resistant prostate cancer; Safety

PMID:
24647231
PMCID:
PMC4418928
DOI:
10.1016/j.eururo.2014.02.056
[Indexed for MEDLINE]
Free PMC Article

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