@article{084ccfc285da43c2ad5033aeb83a610a,
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 = "Abiraterone acetate, Chemotherapy-naive, Efficacy, Metastatic castration-resistant, Safety, prostate cancer",
author = "Rathkopf, {Dana E.} and Smith, {Matthew R.} and {De Bono}, {Johann S.} and Logothetis, {Christopher J.} and Shore, {Neal D.} and {De Souza}, Paul and Karim Fizazi and Mulders, {Peter F.A.} and Paul Mainwaring and Hainsworth, {John D.} and Beer, {Tomasz M.} and Scott North and Yves Fradet and {Van Poppel}, Hendrik and Joan Carles and Flaig, {Thomas W.} and Eleni Efstathiou and Yu, {Evan Y.} and Higano, {Celestia S.} and Taplin, {Mary Ellen} and Griffin, {Thomas W.} and Todd, {Mary B.} and Yu, {Margaret K.} and Park, {Youn C.} and Thian Kheoh and Small, {Eric J.} and Scher, {Howard I.} and Arturo Molina and Ryan, {Charles J.} and Fred Saad",
note = "Funding Information: Financial disclosures: Dana E. Rathkopf certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Dana E. Rathkopf has received research funding from Cougar Biotechnology, Janssen Biotech, and Medivation. Matthew R. Smith has served as a consultant/advisor for, and received research funding from, Janssen. Johann S. de Bono is an employee of The Institute of Cancer Research and has served as a consultant/advisor for and received honoraria from Astellas, Medivation, and Johnson & Johnson. Christopher J. Logothetis has served as a consultant/advisor for, and received honoraria and research funding from, Astellas, Novartis, BMS, Johnson & Johnson, and Sanofi. Neal D. Shore has served as a consultant/advisor for Amgen, Astellas, Algeta, Bayer, Ferring, Dendreon, Janssen, Millennium, Sanofi, and BNI. Paul de Souza has served as a consultant/advisor for, and has received honoraria from, Janssen Australia Pty Ltd. Karim Fizazi has served as a consultant/advisor for, and received honoraria from, Janssen. Paul Mainwaring has served as a consultant/advisor for, and received honoraria from, Roche, Sanofi, and Janssen. Tomasz M. Beer has received research funding from Cougar Biotechnology, Janssen Biotech, Astellas Pharma Global, and Medivation. Scott North has served as a consultant/advisor for Janssen and Astellas and has received honoraria from Janssen, Astellas, Pfizer, Novartis, and GSK. Yves Fradet has received honoraria and research funding from Janssen Ortho. Joan Carles has served as a consultant/advisor for Janssen, Novartis, Sanofi, Pfizer, and Astellas and has received honoraria from Janssen, Astellas, Pfizer, Novartis, and GSK. Thomas W. Flaig is an employee of, and has intellectual property interests in, Aurora Oncology; has served as a consultant/advisor for GTx and Sanofi; and has received honoraria from Amgen and research funding from Amgen, Bayer/Onyx, BN ImmunoTherapeutics, Cougar Biotechnology, Dendreon, Genentech, GlaxoSmithKline, GTx, Janssen Oncology, Medivation, Novartis, Pfizer, Sanofi, Veridex, and Zymogenetics. Eleni Efstathiou has received honoraria from, and served on an ad board and steering committee for, Johnson & Johnson, Millennium, and Sanofi. Evan Y. Yu has served as a consultant/advisor for, and received research funding from, Janssen. Celestia S. Higano has served as a consultant for Amgen, AstraZeneca, Bayer, Centocor Ortho Biotech, Dendreon, Genentech, GTx, Inc., Medivation, Millennium, Pfizer, Bristol-Myers Squibb, Sanofi-Aventis, Teva Pharmaceuticals, Abbott Laboratories, Endo, Fresenius Kabi, Cougar Biotechnology, and Novartis and has received institutional research funding from Amgen, Aragon, Bristol-Myers Squibb, Dendreon, Exelixis, ImClone, Medarex, Medivation, Millennium, OncoGenex, GlaxoSmithKline, Nerviano, Novartis, Cougar Biotechnology, Algeta, and Genentech. Mary-Ellen Taplin has served as a consultant/advisor for, and received honoraria and research funding from, Janssen. Thomas W. Griffin is an employee of Janssen Research & Development and owns stock in Johnson & Johnson. Mary B. Todd is an employee of Janssen Global Services and owns stock in Johnson & Johnson. Margaret K. Yu is an employee of, and owns stock in, Janssen Research & Development. Youn C. Park is an employee of Janssen Research & Development and owns stock in Johnson & Johnson. Thian Kheoh is an employee of Janssen Research & Development and owns stock in Johnson & Johnson. Howard I. Scher has served as a consultant (uncompensated) for Aragon Pharmaceuticals, Bristol-Myers Squibb, Celgene, Johnson & Johnson Pharmaceutical Development, Medivation, and Veridex (now Janssen Research & Development); has served as a consultant (compensated) for ODEON, Enzon, Millennium, Novartis, and Ortho Biotech Oncology Research and Development; and has received research funding (paid to institution) from Aragon Pharmaceuticals, Exelixis, Janssen Research & Development, Medivation, and Veridex (now Janssen Research & Development). Arturo Molina is an employee of Janssen Research & Development and owns stock in Johnson & Johnson. Charles J. Ryan has received honoraria from Janssen. Fred Saad has served as a consultant for, and received honoraria and research funding from, Janssen and Astellas. ",
year = "2014",
month = nov,
day = "1",
doi = "10.1016/j.eururo.2014.02.056",
language = "English (US)",
volume = "66",
pages = "815--825",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "5",
}