Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302).
Eur Urol
; 66(5): 815-25, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-24647231
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, ANDPARTICIPANTS:
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 11 to abiraterone 1000mg plus prednisone 5mg twice daily by mouth versus prednisone. OUTCOME MEASUREMENTS AND STATISTICALANALYSIS:
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 ANDLIMITATIONS:
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. PATIENTSUMMARY:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Esteroide 17-alfa-Hidroxilase
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Protocolos de Quimioterapia Combinada Antineoplásica
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Antineoplásicos Hormonais
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Neoplasias de Próstata Resistentes à Castração
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Inibidores das Enzimas do Citocromo P-450
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Androstenos
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Neoplasias Hormônio-Dependentes
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article