Merseburger, A. S., Scher, H. I., Bellmunt, J., Miller, K., Mulders, P. F. A., Stenzl, A., Sternberg, C. N., Fizazi, K., Hirmand, M., Franks, B., Haas, G. P., de Bono, J., de Wit, R. (2015) Enzalutamide in European and North American men participating in the AFFIRM trial. BJU INTERNATIONAL, 115 (1). pp. 41-49. ISSN 1464-4096

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Abstract

Objective To explore any differences in efficacy and safety outcomes between European (EU) (n = 684) and North American (NA) (n = 395) patients in the AFFIRM trial (NCT00974311). Patients and Methods Phase III, double-blind, placebo-controlled, multinational AFFIRM trial in men with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. Participants were randomly assigned in a 2: 1 ratio to receive oral enzalutamide 160 mg/day or placebo. The primary end point was overall survival (OS) in a post hoc analysis. Results Enzalutamide significantly improved OS compared with placebo in both EU and NA patients. The median OS in EU patients was longer than NA patients in both treatment groups. However, the relative treatment effect, expressed as hazard ratio and 95% confidence interval, was similar in both regions: 0.64 (0.50, 0.82) for EU and 0.63 (0.47, 0.83) for NA. Significant improvements in other end points further confirmed the benefit of enzalutamide over placebo in patients from both regions. The tolerability profile of enzalutamide was comparable between EU and NA patients, with fatigue and nausea the most common adverse events. Four EU patients (4/461 enzalutamide-treated, 0.87%) and one NA patient (1/263 enzalutamide-treated, 0.38%) had seizures. The difference in median OS was related in part to the timing of development of mCRPC and baseline demographics on study entry. Conclusion This post hoc exploratory analysis of the AFFIRM trial showed a consistent OS benefit for enzalutamide in men with mCRPC who had previously progressed on docetaxel in both NA- and EU-treated patients, although the median OS was higher in EU relative to NA patients. Efficacy benefits were consistent across end points, with a comparable safety profile in both regions.

Item Type:	Article
Authors (ICR Faculty only):	De Bono, Johann
All Authors:	Merseburger, A. S., Scher, H. I., Bellmunt, J., Miller, K., Mulders, P. F. A., Stenzl, A., Sternberg, C. N., Fizazi, K., Hirmand, M., Franks, B., Haas, G. P., de Bono, J., de Wit, R.
Additional Information:	ISI Document Delivery No.: AX0OK Times Cited: 0 Cited Reference Count: 29 Merseburger, Axel S. Scher, Howard I. Bellmunt, Joaquim Miller, Kurt Mulders, Peter F. A. Stenzl, Arnulf Sternberg, Cora N. Fizazi, Karim Hirmand, Mohammad Franks, Billy Haas, Gabriel P. de Bono, Johann de Wit, Ronald Astellas Pharma, Inc; Medivation, Inc. The authors had full access to the data and participated in reviewing and interpreting the data and paper. They would like to thank Karen Brayshaw, PhD, at Complete HealthVizion, for assistance with writing and revising the draft manuscript, based on detailed discussion and feedback from all authors. Writing assistance was funded by Astellas Pharma, Inc and Medivation, Inc. Primary responsibility for opinions, conclusions and interpretation of data lies with the authors. All authors read and approved the final version of this manuscript. Wiley-blackwell Hoboken
Uncontrolled Keywords:	androgen receptor inhibitor enzalutamide metastatic castration-resistant prostate cancer resistant prostate-cancer increased survival management association abiraterone strategies guidelines patterns options
Research teams:	ICR divisions > Cancer Therapeutics > Cancer Biomarkers ICR divisions > Clinical Studies > Cancer Biomarkers ICR divisions > Clinical Studies > Prostate Cancer Targeted Therapy Group
Depositing User:	Alexander Smithson
Date Deposited:	30 Jan 2015 16:52
Last Modified:	26 May 2017 10:23
URI:	http://publications.icr.ac.uk/id/eprint/13870

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