5 Background: AA, a specific inhibitor of CYP17, blocks androgen biosynthesis and improves overall survival (OS) in mCRPC post-docetaxel (Lancet Oncol 2012;13:983-92). This pre-specified updated IA (55% total OS events) extends previous IA for COU-AA-302 evaluating clinical benefit of AA vs prednisone (P) in mildly symptomatic or asymptomatic pts with progressive mCRPC without prior chemotherapy.
METHODS
1088 pts were stratified by Eastern Cooperative Oncology Group performance status (ECOG-PS, 0 vs 1) and randomized 1:1 to AA 1000 mg + P 5 mg po BID vs Placebo + P. Co-primary endpoints: radiographic progression-free survival (rPFS) and OS. Median time with 95% CI was estimated using the Kaplan-Meier method. The O'Brien-Fleming Lan-DeMets α-spending function was used for OS.
RESULTS
At 55% IA, OS, rPFS and secondary endpoints all favored the AA arm (Table). Median follow-up = 27.1 mos. A post hoc sensitivity multivariate analysis for OS using known prognostic factors supported primary results (HR 0.74, P = 0.0017). Grade 3/4 AEs (AA, P) (%): hypertension 4.2 vs 3.1; hypokalemia 2.6 vs 1.9; ALT↑ 5.5 vs 0.7; AST↑ 3.1 vs 0.9.
CONCLUSIONS
In updated IA of COU-AA-302, improvement in rPFS (risk reduction 47%) remained statistically significant. Risk of death decreased by 21% but did not reach pre-specified efficacy boundary. Median OS for AA (35.3 mos) is the longest reported for this mCRPC population. Secondary endpoints were clinically and statistically significant; safety profile despite longer exposure remains favorable. Targeting extragonadal androgen synthesis reduces morbidity associated with disease progression in mCRPC pts without prior chemotherapy.
CLINICAL TRIAL INFORMATION
NCT00887198. [Table: see text].