Abiraterone acetate and prednisone in patients (Pts) with progressive metastatic castration resistant prostate cancer (CRPC) after failure of docetaxel-based chemotherapy

Abstract

5019 Background: A proportion of CRPC overexpress androgen synthetic enzymes and are dependent on androgens for growth. Abiraterone acetate (AA) inhibits 17 α-hydroxylase and C17,20-lyase to decrease serum androgen to undetectable levels. Methods: AA plus prednisone was studied in Pts with metastatic CRPC who had progressed on docetaxel based chemotherapy. Pts received oral AA 1000 mg QD, and prednisone 5 mg BID in 28 day cycles. The primary endpoint a >50% decline in PSA from baseline. Changes in bone and soft tissue disease were also monitored, as were pre- and post-therapy circulating tumor cell (CTC) number. Results: 43 Pts were screened and 38 treated. The median (interquartile range) age was 73 years (64–81) and PSA 86.3 ng/mL (33–311.5) while 32 (84%) had > 5 CTC per 7.5 ml of blood at baseline. Prior systemic therapy included 3 or more hormone in 29 (76%), including ketoconazole in 17 (45%); while 26 (68%) received 1, and 12 (32%) 2 lines of chemotherapy. Sites of metastases were bone only in 10 (26%), bone and lymph nodes in 15 (39%), bone and visceral in 11 (29%), while 2 had soft tissue and no bone disease. Of 35 evaluable patients (3 are too early), 11 (31%) progressed within 3 months (m), 9 (26%) within 6 m, and 2 (6%) after 6 m. Seven and 6 pts remain on treatment for 3–6 and 6+ months respectively. At 3 m, 14 of 35 pts (40%, 95% CI 26–57%) achieved a decline in PSA >50% from baseline. CTC were <5 pre- or <5 after therapy in 6 and 11 pts, of whom 3 and 7 are still on treatment; CTC count remained >5 in 21 pts, of whom 15 progressed (P =0.099) There was no grade 3 or 4 hypertension or hypokalemia. One pt discontinued treatment due to transaminitis and myositis. Conclusion: AA plus prednisone is well tolerated and active in progressive CRPC post-chemotherapy. Classifying these patients as hormone-refractory is a misnomer with the potential to deny patients potentially effective treatments. A phase III trial is planned with this regimen. (Supported by Cougar Biotechnology) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cougar Biotechnology Cougar