Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide

Ann Oncol. 2013 Jul;24(7):1802-1807. doi: 10.1093/annonc/mdt138. Epub 2013 Apr 12.

Abstract

Background: Abiraterone acetate and enzalutamide both improve outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). Optimal sequencing for these agents and whether cross-resistance occurs is unknown.

Methods: Multicentre review of patients with mCRPC treated with abiraterone acetate and prednisone after progressing on enzalutamide. Primary objective was to determine abiraterone acetate response.

Results: Thirty patients identified from four North American centres. At abiraterone initiation, median age was 70 years (56-84 years); 70% had ECOG performance status of 0-1; all had prior docetaxel. Median prior enzalutamide treatment duration was 41 weeks (6-95 weeks), with 70% (21 of 30) having a ≥30% prostate-specific antigen (PSA) decline. Median abiraterone acetate treatment duration was 13 weeks (1-52). No objective radiographic responses were observed. Median abiraterone time to progression (PSA, objective or symptomatic) was 15.4 weeks [95% confidence interval (CI) 10.7-20.2]. Median overall survival was 50.1 weeks (95% CI 28.3-72.0). Three patients had a ≥30% PSA decline with abiraterone. Two of these patients had PSA progression as best response with prior enzalutamide.

Conclusions: In this study of patients progressing after enzalutamide, treatment with abiraterone was associated with a modest response rate and brief duration of effect. Primary progression on enzalutamide may not preclude a response to abiraterone.

Keywords: abiraterone acetate; castration-resistant; enzalutamide; prostatic neoplasms.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenes
  • Androstenols / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Disease-Free Survival
  • Drug Resistance, Neoplasm
  • Humans
  • Kallikreins / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nitriles
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / pharmacology
  • Phenylthiohydantoin / therapeutic use
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Androstenes
  • Androstenols
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Phenylthiohydantoin
  • enzalutamide
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • abiraterone