Exploring the Clinical Benefit of Docetaxel or Enzalutamide After Disease Progression During Abiraterone Acetate and Prednisone Treatment in Men With Metastatic Castration-Resistant Prostate Cancer

Clin Genitourin Cancer. 2015 Aug;13(4):392-399. doi: 10.1016/j.clgc.2015.01.004. Epub 2015 Jan 24.

Abstract

Background: Abiraterone acetate (AA) has demonstrated improved outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). However, data are lacking on the effect of AA on subsequent efficacy of enzalutamide or docetaxel.

Patients and methods: We included men with mCRPC who received AA and subsequent enzalutamide or docetaxel by August 12, 2013. Patients were separated into 3 groups: group A, treated with AA then enzalutamide before chemotherapy; group B, treated with AA then docetaxel; and group C, treated with AA and enzalutamide after chemotherapy. The primary objective was to describe the response and overall survival with subsequent therapy.

Results: There were 28 evaluable patients who received enzalutamide after AA (9 in group A and 19 in group C) and 13 patients who received docetaxel after AA (group B). Group A patients had more visceral disease and higher baseline prostate-specific antigen (PSA) levels, and group C men had a higher level of pain and multiple poor prognostic features. Median progression-free survival was 3.6, 5.1, and 2.8 months, respectively, and median overall survival was 8.5, not reached, and 9.6 months, respectively. A ≥ 50% PSA decline was achieved in 11%, 63%, and 5% of group A, B, and C patients, respectively. Radiographic or clinical progression as best response was noted in 55.5%, 30.8%, and 68.4% in each respective group.

Conclusion: In this chart review of consecutive men with progressive mCRPC after AA, we found modest activity for enzalutamide and docetaxel, with clear cross-resistance for AA and enzalutamide. These data might inform the complex treatment decisions after AA treatment.

Keywords: Abiraterone; Castration resistant prostate cancer; Cross-resistance; Docetaxel; Enzalutamide.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Abiraterone Acetate
  • Aged
  • Aged, 80 and over
  • Androstenes / pharmacology*
  • Androstenes / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Disease Progression
  • Disease-Free Survival
  • Docetaxel
  • Drug Resistance, Neoplasm
  • Humans
  • Kallikreins / blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nitriles
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / therapeutic use
  • Prednisone / pharmacology*
  • Prednisone / therapeutic use
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / diagnostic imaging
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Radiography
  • Retrospective Studies
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Androstenes
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • enzalutamide
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • Abiraterone Acetate
  • abiraterone
  • Prednisone