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

Lauren C. Harshman, Lillian Werner, Abhishek Tripathi, Xiaodong Wang, Benjamin L. Maughan, Emmanuel S. Antonarakis, Mari Nakabayashi, Rana McKay, Mark Pomerantz, Lorelei A. Mucci, Mary Ellen Taplin, Christopher J. Sweeney, Gwo Shu Mary Lee, Philip W. Kantoff

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1303-1311
Number of pages9
JournalProstate
Volume77
Issue number13
DOIs
StatePublished - Sep 15 2017

Keywords

  • SLCO transport
  • abiraterone acetate
  • duration
  • prostate cancer
  • statins

ASJC Scopus subject areas

  • Oncology
  • Urology

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