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

TY - JOUR

T1 - Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone

T2 - A Multicentre Analysis

AU - Brasso, Klaus

AU - Thomsen, Frederik B

AU - Schrader, Andres J

AU - Schmid, Sebastian C

AU - Lorente, David

AU - Retz, Margitta

AU - Merseburger, Axel S

AU - von Klot, Christoph A

AU - Boegemann, Martin

AU - de Bono, Johann

N1 - Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

PY - 2015/8/1

Y1 - 2015/8/1

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Androgen Antagonists

KW - Androstenes

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Compassionate Use Trials

KW - Disease Progression

KW - Disease-Free Survival

KW - Drug Resistance, Neoplasm

KW - Drug Substitution

KW - Europe

KW - Humans

KW - Kallikreins

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Phenylthiohydantoin

KW - Proportional Hazards Models

KW - Prostate-Specific Antigen

KW - Prostatic Neoplasms, Castration-Resistant

KW - Risk Factors

KW - Taxoids

KW - Time Factors

KW - Treatment Outcome

U2 - 10.1016/j.eururo.2014.07.028

DO - 10.1016/j.eururo.2014.07.028

M3 - Journal article

C2 - 25108579

SN - 0302-2838

VL - 68

SP - 317

EP - 324

JO - European Urology

JF - European Urology

IS - 2

ER -