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

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 vs. 9.2 mo (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 vs. 8.0 months (HR 0.89, 95% CI: 0.69–1.16, p=0.38) in the statin users vs. 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 towards 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.

Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide after docetaxel failure: the international retrospective observational STABEN study

“…In one small retrospective study, statin use was significantly associated with longer OS and early PSA declines in men who received abiraterone [ 8 ]. In contrast, this OS advantage has not been consistently observed in other studies [ 9 , 10 ]. Furthermore, there is prospective evidence from a phase III trial suggesting that statins may be discontinued in the palliative care setting with no detrimental effect on survival [ 11 ].…”

“…This was supported by their retrospective clinical study of 926 patients, treated with androgen deprivation, which demonstrated that patients who received statin therapy experienced longer median time to progression, when compared to patients not treated with a statin (27.5 versus 17.4 months; P < 0.001). Because abiraterone is also a SLCO2B1 substrate, the same research group [ 10 ] hypothesized that statin use could be a negative predictive factor for patients taking abiraterone. However, their retrospective study of 224 abiraterone-treated patients demonstrated that statin use trended toward longer treatment duration (14.2 versus 9.2 months; HR: 0.79, 95% CI, 0.57–1.09, P = 0.14).…”

“…However, their retrospective study of 224 abiraterone-treated patients demonstrated that statin use trended toward longer treatment duration (14.2 versus 9.2 months; HR: 0.79, 95% CI, 0.57–1.09, P = 0.14). Despite lack of validation in an independent cohort of 270 abiraterone-treated patients [ 10 ], the authors concluded that concomitant stain use did not negatively impact survival.…”

Germline Variant in SLCO2B1 and Response to Abiraterone Acetate Plus Prednisone (AA) in New-onset Metastatic Castration-resistant Prostate Cancer (mCRPC)

“…Thus, many hypothesized that statins could interfere with abiraterone acetate efficacy because both drugs are transported by SLCO2B1. However, a multi-institutional, retrospective study by Harsman and colleagues showed that statins do not interfere with abiraterone acetate efficacy (10). In addition to its previously discussed roles, the SNP rs12422149 of SLCO2B1 is a validated, predictive biomarker of response to ADT for biochemically recurrent and mHSPC (Table 3; SLCO2B1 is a prognostic biomarker of improved outcomes in metastatic prostate cancer.…”

New Insights in Prostate Cancer Development and Tumor Therapy: Modulation of Nuclear Receptors and the Specific Role of Liver X Receptors

“…A decrease in the time of response to ADT has also been reported in patients with hypercholesterolemia. Conversely, statins delay the emergence of CRPC in ADT treated patients [ 142 ]. However, it should be kept in mind that statins have numerous side effects.…”