The impact of statin use on abiraterone acetate (AA) treatment duration in patients with castration-resistant prostate cancer (CRPC).

Abstract

196 Background: Statins compete with DHEAS for influx through the transporter SLCO2B1 and may prolong time to progression (TTP) on androgen deprivation therapy (ADT). The androgen biosynthesis inhibitor, AA, may also undergo SLCO-mediated transport. We hypothesized that statins may compete with AA for influx by SLCO2B1, which could negatively impact drug efficacy. Methods: We queried our institutional clinical database for patients treated with AA for CRPC. Data on statin use including on-therapy dates were retrospectively collected from the medical record. Time on AA was used as a surrogate for TTP. Duration of AA was defined as the time from AA initiation to time to when AA was discontinued or censored on the last known alive date. The association between statin use and AA duration was estimated using the Kaplan-Meier method. Multivariable Cox regression adjusted for known prognostic factors (e.g, prior docetaxel (D) or enzalutamide (E) use, and sites of metastases (mets) specifically bone or lymph node versus liver or other viscera. Results: Of the 224 patients eligible for analysis, the majority (96%) had metastatic disease at time of AA initiation. 26% had prior D and 7% E. Nearly half were statin users (41%). The median duration on AA was 10.7 months (mo) with a trend to longer duration in statin users: 14.2 vs. 9.2 mo (HR 0.79, 95% CI: 0.57-1.09, p = 0.14). Prior D and E was significantly associated with shorter AA duration while site of mets and age were not. Adjusting for prior use of D, E, and site of mets did not alter the relationship between statin use and AA duration (p = 0.18, HR 0.81, 0.58-1.11). Conclusions: Contrary to our initial hypothesis, there was a trend to longer AA duration in statin users. Given our prior work demonstrating a 10 mo prolonged TTP on ADT in men concurrently taking statins (adjusted HR 0.83), and in vitro findings of inhibition of DHEAS uptake by statins, we postulate that there could be an additive effect of statins and AA by blocking DHEAS uptake. Alternatively, statins may inhibit hepatic AA uptake prolonging drug exposure and increasing effectiveness. Ongoing analyses are evaluating the impact of SLCO SNPs on AA efficacy.