The Phase 3 COU-AA-302 Study of Abiraterone Acetate Plus Prednisone in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Stratified Analysis Based on Pain, Prostate-specific Antigen, and Gleason Score

Background: In the COU-AA-302 study (NCT00887198), abiraterone acetate plus prednisone (AAP) significantly improved outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) versus prednisone alone. Baseline clinical parameters predicting that treatment response could help inform clinical decisions were explored. Objective: To identify patients who derive the greatest clinical benefit from AAP treatment. Design, setting, and participants: A total of 1088 mCRPC patients treated with either AAP or prednisone in the first-line setting in COU-AA-302 were included in this post hoc analysis. Intervention: Abiraterone acetate1000 mg daily versus placebo, both plus prednisone 10 mg daily. Outcome measurements and statistical analysis: Univariate and multivariable Cox regression analyses were performed, including clinical and pathological parameters for the primary end points overall survival (OS) and radiographic progression-free survival (rPFS), and secondary study end points. Tumor-associated baseline parameters independently impacting OS were applied to stratify patients according to possible treatment effects. Results and limitations: Baseline prostate-specific antigen (PSA), tumor-related pain as assessed by the Brief Pain Inventory-Short Form (BPI-SF), and Gleason score (GS) at primary diagnosis were identified as tumor-associated variables that independently impacted OS. AAP significantly improved outcomes versus prednisone in both group 1 (BPI-SF 0–1 and PSA <80 ng/ml and GS <8; p = 0.006; hazard ratio [HR]: 0.61) and group 2 (BPI-SF 2–3 and/or PSA ≥80 ng/ml and/or GS ≥8; p = 0.03; HR: 0.84). The differences observed for treatment effects between groups 1 and 2 for OS (HR: 0.61 vs 0.84), rPFS (HR: 0.41 vs 0.59), and time to chemotherapy (HR: 0.64 vs 0.71) were not statistically significant. Conclusions: AAP significantly improved outcomes in mCRPC patients compared with prednisone alone regardless of baseline pain and PSA level, and GS at primary diagnosis with no significant differences between observed treatment effects in groups 1 and 2. Patient summary: Treatment with abiraterone acetate and prednisone (compared with treatment with prednisone only) for metastatic castration-resistant prostate cancer increased survival in all patients in the study regardless of pain, prostate-specific antigen levels at the start of treatment, and Gleason score at primary diagnosis. This post hoc analysis of the pivotal COU-AA-302 study shows that abiraterone acetate plus prednisone significantly improves outcomes in patients with metastatic castration-resistant prostate cancer regardless of baseline characteristics. The observed treatment effects in patients at an early versus advanced disease stage were not significantly different.