Randomized double-blind, comparative study of abiraterone acetate (AA) plus low-dose prednisone (P) plus androgen deprivation therapy (ADT) versus ADT alone in newly diagnosed, high-risk, metastatic hormone-naive prostate cancer (mHNPC).

TPS5097 Background: Patients (pts) who initially present with metastatic prostate cancer (MPC) (up to 30% of men in Europe; 4% in US) typically progress to metastatic castration-resistant prostate cancer (mCRPC) with a poor prognosis. Prognostic factors impacting survival include high PSA concentration, high Gleason score, high volume of metastatic disease, and bone symptoms. AA decreases testosterone via CYP17 inhibition and is approved for treatment of mCRPC before and after docetaxel-based chemotherapy. Two recent reports (J Clin Oncol. 2012: 30 [suppl. abstr 4521 and 4556]) showed that AA + P in addition to ADT (LHRH agonist) in the neoadjuvant setting led to higher rates of undetectable PSA and complete pathologic response (cPR) or near-cPR in pts undergoing prostatectomy for high risk-localized prostate cancer than with ADT alone, suggesting a potential role for inhibiting extragonadal androgen synthesis prior to emergence of castration-resistance. Because of its benefit in mCRPC, as well as early activity in high risk-localized prostate cancer, AA is being evaluated in high risk mHNPC. Methods: Approximately 1,270 men with newly diagnosed (within 3 months of randomization) high risk mHNPC with at least 2 of 3 high risk factors (≥ 3 bone lesions, presence of visceral metastases or Gleason score ≥ 8) are being randomized to AA 1000 mg + P 5 mg daily + ADT or ADT alone. Pts are stratified by presence of visceral disease and ECOG PS (0-1 vs 2). Distant metastatic disease must be documented by positive bone scan or CT/MRI. ADT or orchiectomy within 3 mos of randomization is allowed. Continued use of anti-androgens after randomization is not allowed on study. The primary endpoint is overall survival. Secondary endpoints include radiographic PFS, time to next skeletal-related event, PSA progression, and subsequent therapy. Two interim analyses and a final analysis are planned. 300 sites from 36 countries will participate. As of February 4, 2013, one patient has entered screening. Clinical trial information: NCT01715285.