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.
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.
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).
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.
The Prostate. 2017 Aug 01 [Epub ahead of print]
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
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts., Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland., Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.