Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COU-AA-302)

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...

Full description

Saved in:
Bibliographic Details
Published in:European urology 2014-11, Vol.66 (5), p.815-825
Main Authors: Rathkopf, Dana E, Smith, Matthew R, de Bono, Johann S, Logothetis, Christopher J, Shore, Neal D, de Souza, Paul, Fizazi, Karim, Mulders, Peter F.A, Mainwaring, Paul, Hainsworth, John D, Beer, Tomasz M, North, Scott, Fradet, Yves, Van Poppel, Hendrik, Carles, Joan, Flaig, Thomas W, Efstathiou, Eleni, Yu, Evan Y, Higano, Celestia S, Taplin, Mary-Ellen, Griffin, Thomas W, Todd, Mary B, Yu, Margaret K, Park, Youn C, Kheoh, Thian, Small, Eric J, Scher, Howard I, Molina, Arturo, Ryan, Charles J, Saad, Fred
Format: Article
Language:English
Subjects:
Abiraterone Acetate
Aged
Androstenes - administration & dosage
Androstenes - adverse effects
Antineoplastic Agents, Hormonal - administration & dosage
Antineoplastic Agents, Hormonal - adverse effects
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biological and medical sciences
Chemotherapy-naive
Cytochrome P-450 Enzyme Inhibitors - administration & dosage
Cytochrome P-450 Enzyme Inhibitors - adverse effects
Disease Progression
Disease-Free Survival
Double-Blind Method
Drug Administration Schedule
Efficacy
Gynecology. Andrology. Obstetrics
Humans
Kaplan-Meier Estimate
Male
Male genital diseases
Medical sciences
Metastatic castration-resistant prostate cancer
Middle Aged
Neoplasm Metastasis
Neoplasms, Hormone-Dependent - drug therapy
Neoplasms, Hormone-Dependent - enzymology
Neoplasms, Hormone-Dependent - mortality
Neoplasms, Hormone-Dependent - pathology
Nephrology. Urinary tract diseases
Prednisone - administration & dosage
Proportional Hazards Models
Prostatic Neoplasms, Castration-Resistant - drug therapy
Prostatic Neoplasms, Castration-Resistant - enzymology
Prostatic Neoplasms, Castration-Resistant - mortality
Prostatic Neoplasms, Castration-Resistant - pathology
Risk Factors
Safety
Steroid 17-alpha-Hydroxylase - antagonists & inhibitors
Steroid 17-alpha-Hydroxylase - metabolism
Time Factors
Treatment Outcome
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
Urology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 1000 mg plus prednisone 5 mg 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 numb
ISSN:0302-2838
1873-7560
DOI:10.1016/j.eururo.2014.02.056