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Prostate Cancer

Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone: A Multicentre Analysis

By: Klaus Brasso a , Frederik B. Thomsen a , Andres J. Schrader b , Sebastian C. Schmid c , David Lorente d , Margitta Retz c , Axel S. Merseburger e , Christoph A. von Klot e , Martin Boegemann f and Johann de Bono d

European Urology, Volume 68 Issue 2, August 2015, Pages 317-324

Published online: 01 August 2015

Keywords: Castration-resistant prostate cancer, Enzalutamide, Abiraterone, Docetaxel, Survival, PSA

Abstract Full Text Full Text PDF (1,1 MB) Patient Summary

Abstract

Background

The degree of antitumour activity of enzalutamide following disease progression on docetaxel and abiraterone remains controversial.

Objective

To examine the effect of enzalutamide in patients progressing following taxane-based chemotherapy and abiraterone.

Design, setting, and participants

Metastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide.

Outcome measurements and statistical analysis

The primary end point was overall survival (OS). Secondary end points were association between OS and posttreatment prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed.

Results and limitations

We identified 137 patients who prior to enzalutamide had progressed following a median of eight cycles of docetaxel and seven courses of abiraterone. The median time on enzalutamide was 3.2 mo; median OS from the time patients started enzalutamide was 8.3 mo (95% confidence interval, 6.8–9.8). Only 45 (38%) and 22 (18%) patients had PSA declines (unconfirmed) >30% and 50%, respectively. Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p = 0.001 and 12.6 vs 7.4 mo; p = 0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS.

Conclusions

Median OS on enzalutamide following disease progression on taxane-based chemotherapy and abiraterone was modest, but patients who experience a PSA decline >30% or 50%, respectively, with enzalutamide in this setting had longer survival.

Patient summary

Enzalutamide produces modest prostate-specific antigen (PSA) responses in patients progressing following chemotherapy and abiraterone. Despite a modest PSA response, survival may still be improved.

Take Home Message

A combined European analysis of patients who have castration-resistant prostate cancer previously managed with both docetaxel and abiraterone demonstrated a potential benefit in terms of prolonged survival when entering a compassionate use programme with enzalutamide, despite modest prostate-specific antigen response.

Keywords: Castration-resistant prostate cancer, Enzalutamide, Abiraterone, Docetaxel, Survival, PSA.

Footnotes

a Copenhagen Prostate Cancer Centre, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark

b Department of Urology, Ulm University Medical Centre, Ulm, Germany

c Urologische Klinik und Poliklinik, Technische Universität München, Munich, Germany

d Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Sutton, United Kingdom

e Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany

f Department of Urology, Muenster University Medical Centre, Muenster, Germany

Corresponding author. Copenhagen Prostate Cancer Centre, Rigshospitalet, Tagensvej 20, Afsnit 7521, Copenhagen N, DK-2200, Denmark. Tel. +45 35 457 125; Fax: +45 35 452 716.

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