Background: Abiraterone acetate (AA), an androgen biosynthesis inhibitor, prolongs overall survival (OS) in mCRPC patients and is approved for use in this population. The relationship of PSA kinetics to rPFS was evaluated in an exploratory analysis of patients from COU-AA-302, a randomized phase III study of AA in chemotherapy-naive mCRPC patients. Methods: 1,088 patients were randomized 1:1 to AA (1 g) + prednisone (P) (5 mg BID) or P alone. rPFS and OS were co-primary endpoints. rPFS was defined as time to first occurrence of bone scan progression by PCWG2 criteria, progression by CT/MRI by modified RECIST 1.0 criteria, or death from any cause; PSA changes were not a factor in determining rPFS. Quartiles of baseline PSA and % PSA decrease from baseline to nadir were analyzed. Stratified Cox regression models were used with factors for treatment, PSA outcomes, and baseline covariates performed at 55% of OS events. Results: 54/546 patients (10%) in AA + P arm achieved undetectable PSA vs 14/542 patients (3%) in the P arm; at median follow-up of 27.1 mos, radiographic progression was observed in 28% (AA + P) vs 50% of patients (P). There was a consistent trend of decreasing hazard of progression with decreasing baseline PSA and increasing % PSA decline (Table). Treatment effect of AA + P vs P with decreasing baseline PSA or % PSA decline remained significant (p=0.001) after adjusting for other factors (PSA, LDH, alk phos, hemoglobin, bone metastasis) in the model. Conclusions: rPFS was positively associated with the magnitude of PSA decline and inversely associated with baseline PSA. These effects remained after correcting for covariates. In all analyses, treatment with AA led to rPFS outcomes superior to P. Clinical trial information: NCT00887198.

^a vs ≥ 106; ^b vs no ↓