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

Eur Urol. 2015 Aug;68(2):317-24. doi: 10.1016/j.eururo.2014.07.028. Epub 2014 Aug 6.

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.

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

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / adverse effects
  • Androgen Antagonists / therapeutic use*
  • Androstenes / adverse effects
  • Androstenes / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Compassionate Use Trials
  • Disease Progression
  • Disease-Free Survival
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Drug Substitution
  • Europe
  • Humans
  • Kallikreins / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nitriles
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / therapeutic use
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Risk Factors
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Androstenes
  • Benzamides
  • Nitriles
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • enzalutamide
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • abiraterone