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
Externally publishedYes

Bibliographical note

Funding Information:
LC Harshman: Advisory: Genentech, Dendreon, Pfizer, Medivation/Astellas, Kew Group, Theragene; Research to the institution: Bayer, Sotio, BMS, Merck, Takeda, Dendreon/Valient, Jannsen, Medivation/Astellas, Genentech, Pfizer, Takeda, Jannsen; Travel accommodations: Sanofi; L Werner: None; A Tripathi: None; X Wang: None; BL Maughan: None; ES Antonarakis: Honoraria: Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA, Astellas Pharma; Consultant/adviser: Sanofi, Dendreon, Medivation, Janssen Biotech, ESSA, Astellas Pharma; Research funding to institution: Janssen Biotech, Johnson & Johnson, Sanofi, Dendreon, Aragon Pharmaceuticals, Exelixis, Millenium Pharm, Genentech, Novartis, Astellas Pharmaceuticals, and Tokai Pharma; Patents: Co-inventor of a biomarker technology that has been licensed to Qiagen and Tokai; Travel/Accommodations/Expenses: Sanofi, Dendreon, MedivationM Nakabayashi: None; R McKay: Research funding to institution: Bayer, Pfizer; M Pomerantz: None; LA Mucci: none; ME Taplin: Research funding and advisory board: Janssen; CJ Sweeney: Consulting and research support: Janssen, Astellas, Medivation, Bayer, Sanofi; Consulting; Pfizer; GSM Lee: None; PW Kantoff: Consultant: Astellas, Bayer, Bellicum, BIND Biosciences Inc., BN Immunotherapeutics, DRGT, Genetech/Roche, Ipsen Pharmaceuticals, Janssen, Metamark, Merck, MTG Therapeutics, Omnitura, OncoCellMDX, OncoGenex, Progenity, Sanofi, Tarveda Therapeutics, Thermo Fisher, Bavarian Nordic; Investments: Bellicum, DRGT, Placon, Tarveda Therapeutics; Editorial services: UpToDate; Advisory board: Memorial Sloan kettering Cancer Center, University of Pennsylvania, Thomas Jefferson University, MD Anderson Cancer Center, Northwestern University. This work was supported by a Dana-Farber Prostate Cancer SPORE P50CA090381; Department of Defense (DOD - W81XWH-14-1-0515). Lauren C. Harshman was partially funded by a 2013 Prostate Cancer Foundation Young Investigator Award. Benjamin L. Maughan was partially funded by a Conquer Cancer Foundation YIA. Emmanuel S. Antonarakis was partially funded by grant P30 CA006973.

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

Keywords

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

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