Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone

Eur J Cancer. 2014 Jan;50(1):78-84. doi: 10.1016/j.ejca.2013.08.020. Epub 2013 Sep 25.

Abstract

Background: The new generation anti-androgen enzalutamide and the potent CYP17 inhibitor abiraterone have both demonstrated survival benefits in patients with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. Preliminary data on the antitumour activity of abiraterone after enzalutamide have suggested limited activity. The antitumour activity and safety of enzalutamide after abiraterone in metastatic CRPC patients is still unknown.

Patients and methods: We retrospectively identified patients treated with docetaxel and abiraterone prior to enzalutamide to investigate the activity and safety of enzalutamide in a more advanced setting. Prostate specific antigen (PSA), radiological and clinical assessments were analysed.

Results: 39 patients with metastatic CRPC were identified for this analysis (median age 70years, range: 54-85years). Overall 16 patients (41%) had a confirmed PSA decline of at least 30%. Confirmed PSA declines of ⩾50% and ⩾90% were achieved in 5/39 (12.8%) and 1/39 (2.5%) respectively. Of the 15 patients who responded to abiraterone, two (13.3%) also had a confirmed ⩾50% PSA decline on subsequent enzalutamide. Among the 22 abiraterone-refractory patients, two (9%) achieved a confirmed ⩾50% PSA decline on enzalutamide.

Conclusion: Our preliminary case series data suggest limited activity of enzalutamide in the post-docetaxel and post-abiraterone patient population.

Keywords: Abiraterone; Androgen receptor targeting; Castration resistant prostate cancer; Enzalutamide; Hormone therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenes
  • Androstenols / adverse effects
  • Androstenols / therapeutic use*
  • Docetaxel
  • Humans
  • Male
  • Middle Aged
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives*
  • Phenylthiohydantoin / therapeutic use
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / metabolism
  • Retrospective Studies
  • Taxoids / adverse effects
  • Taxoids / therapeutic use*
  • Treatment Outcome

Substances

  • Androstenes
  • Androstenols
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • enzalutamide
  • Prostate-Specific Antigen
  • abiraterone