The impact of statin use on the efficacy of abiraterone acetate in patients with castration-resistant prostate cancer

Prostate. 2017 May;77(13):1303-1311. doi: 10.1002/pros.23390. Epub 2017 Aug 1.

Abstract

Background: Statins compete with DHEAS for influx through the SLCO2B1 transporter, which may prolong time to progression (TTP) on androgen deprivation therapy. Abiraterone acetate (AA) may also undergo SLCO-mediated transport. Based on preclinical findings showing antagonism, we hypothesized that statins may compete with AA for influx via SLCO2B1 and could negatively impact drug efficacy.

Methods: We queried two institutional clinical databases (Dana-Farber Cancer Institute [DFCI], Johns Hopkins University [JHU]) for CRPC patients treated with AA. Treatment duration was a surrogate for TTP. Associations between statin use and AA duration were estimated using the Kaplan-Meier method. Multivariable Cox regression modeling adjusted for known prognostic factors.

Results: Of the 224 DFCI and 270 JHU patients included, the majority (96%) had metastatic disease. Nearly half (41% and 45%) were statin users. In the DFCI cohort, there was a trend toward longer AA duration in statin users: 14.2 versus 9.2 months (HR 0.79, 95%CI: 0.57-1.09, P = 0.14). There was no association between statin use and AA duration in the JHU cohort: 8.3 versus 8.0 months (HR 0.89, 95%CI: 0.69-1.16, P = 0.38) in the statin users versus non-users, except for a trend in patients that had not previously received docetaxel or enzalutamide (HR 0.79; 95%CI: 0.57-1.10).

Conclusions: Contrary to our initial hypothesis, there was a trend toward longer (rather than shorter) AA duration in statin users in the entire DFCI cohort and in the enzalutamide- and docetaxel-naïve JHU patients. Together, these results do not support the hypothesis that statins interfere with AA efficacy.

Keywords: SLCO transport; abiraterone acetate; duration; prostate cancer; statins.

MeSH terms

  • Abiraterone Acetate* / administration & dosage
  • Abiraterone Acetate* / pharmacokinetics
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Biological Transport / drug effects*
  • Cell Line
  • Disease Progression
  • Docetaxel
  • Drug Synergism
  • Electronic Health Records / statistics & numerical data
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacokinetics
  • Male
  • Middle Aged
  • Organic Anion Transporters / metabolism*
  • Phenylthiohydantoin / analogs & derivatives
  • Phenylthiohydantoin / therapeutic use
  • Prostate-Specific Antigen / analysis
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / metabolism
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Retrospective Studies
  • Taxoids / therapeutic use
  • Time Factors
  • United States

Substances

  • Antineoplastic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Organic Anion Transporters
  • SLCO2B1 protein, human
  • Taxoids
  • Docetaxel
  • Phenylthiohydantoin
  • enzalutamide
  • Prostate-Specific Antigen
  • Abiraterone Acetate