Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302) Journal Article
| Authors: | Rathkopf, D. E.; Smith, M. R.; de Bono, J. S.; Logothetis, C. J.; Shore, N. D.; De Souza, P.; Fizazi, K.; Mulders, P. F. A.; Mainwaring, P.; Hainsworth, J. D.; Beer, T. M.; North, S.; Fradet, Y.; Van Poppel, H.; Carles, J.; Flaig, T. W.; Efstathiou, E.; Yu, E. Y.; Higano, C. S.; Taplin, M. E.; Griffin, T. W.; Todd, M. B.; Yu, M. K.; Park, Y. C.; Kheoh, T.; Small, E. J.; Scher, H. I.; Molina, A.; Ryan, C. J.; Saad, F. |
| Article Title: | 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: | 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 a-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 (a-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. 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 patientswithmCRPC fromApril 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. |
| Keywords: | prostate cancer; safety; abiraterone acetate; efficacy; chemotherapy-naive; metastatic castration-resistant |
| Journal Title: | European Urology |
| Volume: | 66 |
| Issue: | 5 |
| ISSN: | 0302-2838 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2014-11-01 |
| Start Page: | 815 |
| End Page: | 825 |
| Language: | English |
| DOI: | 10.1016/j.eururo.2014.02.056 |
| PROVIDER: | scopus |
| PUBMED: | 24647231 |
| PMCID: | PMC4418928 |
| DOI/URL: | |
| Notes: | Export Date: 3 November 2014 -- Source: Scopus |
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