Phase II multicenter study of chemotherapy (chemo)-naive castration-resistant prostate cancer (CRPC) not exposed to ketoconazole (keto), treated with abiraterone acetate (AA) plus prednisone
5046 Background: AA is a potent inhibitor of the enzyme CYP17, a major contributor to androgen biosynthesis. Keto is also known to inhibit this enzyme but AA is many-fold stronger in its action. 33 pts with progressive metastatic disease, normal organ function, ECOG performance status (PS) 0–1, and no prior chemo were enrolled. Pts with prior keto treatment were excluded. AA (1000 mg qd) plus prednisone (5mg bid) were administered orally in 28 day cycles. Methods: Results: At baseline median age was 71.0 (range 52–85) yrs and median PSA was 24.7 (range 7.1–1110.0) ng/mL;19/26 pts (73%) had an ECOG PS of 0 and 7/26 (27%) had PS of 1; the median number of prior hormonal therapies was 2; all pts were on LHRHa and 73% of pts had received anti-androgen, all of whom had undergone prior anti-androgen withdrawal. Pts were evaluated at each cycle for PSA response according to PSAWG criteria. 27 pts have available data for PSA response. Total maximal PSA declines of ≥30%, ≥50%, ≥90% were observed in 89% (24/27), 85% (23/27) and 41% (11/27) pts, respectively. Week 12 PSA declines displayed a similar and sustained trend: ≥30%, ≥50% and ≥90% PSA decline in 82%, 78%, and 26% of pts. Post-treatment ECOG PS score was 0 in 24 (92%) pts: 19% experienced improvement in PS (PS 1 to 0 in 5 pts) and 19/19 pts maintained a PS of 0; Median time to PSA progression has not been reached. Majority of adverse events were grades 1–2. Incidence of hypokalemia - 12%; HTN - 6%; edema - 15%. One pt experienced a grade 3 drug-related HTN. Conclusions: Abiraterone acetate plus prednisone has significant anti-cancer activity in patients with metastatic CRPC not previously treated with ketoconazole or chemotherapy, as demonstrated by declines in PSA and improvement in performance status, and is well-tolerated. [Table: see text]