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.
Bibliographical noteFunding 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.
© 2017 Wiley Periodicals, Inc.
- abiraterone acetate
- prostate cancer
- SLCO transport