Enzalutamide (ENZA) in combination with abiraterone acetate (AA) in bone metastatic castration resistant prostate cancer (mCRPC).

5000 Background: Co-targeting the androgen receptor (AR) and paracrine androgen biosynthesis in mCRPC may be more effective than either alone. This study aims to evaluate safety, pharmacokinetic (PK) drug-drug interactions (DDI), androgen signaling and steroid metabolome modulation and efficacy of ENZA with AA in mCRPC Methods: We enrolled patients (pts) with progressive bone mCRPC, castrate level serum testosterone (≤ 50 ng/dl) consenting to bone marrow (BM) biopsy. Pts were treated with ENZA 160 mg QD and AA 1g QD + prednisone 5 mg bid and monitored every 4-week with CBC, chemistry, physical exams. mCRPC was assessed clinically by PSA, ALP and imaging. Tumor was characterized by IHC and LC mass spectrometry (blood and BM). Ctroughplasma concentrations of AA were measured on days 4 & 29, and ENZA and its active metabolite M2 on d29 in pt subset. Results: We enrolled (07/12-09/13) 60 pts with median age 66 yrs (range 40-82), PS-ECOG 1 (range 0-2) and PSA 20.8 ng/ml (range1-670). Gleason Score (GS) at diag...