Response to ketoconazole (keto) or docetaxel (D) following clinical progression on abiraterone acetate (AA) in castrate-resistant prostate cancer (CRPC).

Abstract

4664 Background: Patients (pts) with CRPC treated with keto often experience a rise in serum adrenal androgen levels upon progression and may subsequently respond to more potent adrenal suppression with AA. In contrast, pts treated with AA do not have a rise in serum androgen levels upon progression, and thus may not respond to further androgen synthesis inhibition with keto but require other treatment modalities such as chemotherapy instead. The goal of this analysis is to report the outcomes of pts with CRPC progressing on AA subsequently treated with either keto or D. Methods: Pts with chemotherapy-naïve CRPC were treated on previously reported phase 1 and 2 trials of AA, with doses ranging from 250 to 1000 mg/day. Subsequent treatment following progression on AA was per individual investigator discretion, including treatment with either keto or D. Results: To date, following disease progression on AA, 6 and 14 pts have been subsequently treated with either keto or D respectively. Of the 14 pts treated with D, 11 (79%) had exposure to keto prior to AA. The keto- and D-treated cohorts were similar with respect to other baseline factors, including prior response to AA (4/6 (67%) pts with > 50% PSA decline on AA in keto cohort; 10/14 (71%) pts in D cohort); though pts treated with D were more likely to require opioid analgesics (0 pts in keto cohort; 7 (50%) in D). For pts treated with keto, none experienced a decline in PSA, improvement in bone scan, or an objective response; all had disease progression by 12 weeks. In contrast, for pts treated with D, 10 (71%) had a decline in PSA; 6 (43%) with a > 50% maximum PSA decline. Of 6 pts with measurable disease, 2 (33%) had an objective response. The median time to progression for the D cohort was 129 days (range 60 – 294). Conclusions: Although the cohort size is small, and post-AA therapy was not randomized, these data provide preliminary support for the hypothesis that CRPC progressing on AA is cross-resistant to further androgen synthesis inhibition with keto. Contrary to other reports, prior treatment with AA does not appear to decrease the likelihood of subsequent response to D, but this observation requires prospective validation.