Survival outcome of chemotherapy-naïve castration-resistant prostate cancer treated with new-generation androgen receptor axis-targeted agents in real-world analysis

Abstract Purpose The androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide have been introduced against castration-resistant prostate cancer (CRPC). However, determining which of these agents should be used first is a clinical challenge. Therefore, in this study, we compared the efficacy of first-line abiraterone and enzalutamide treatments in chemotherapy-naïve patients with CRPC. Methods A total of 242 chemotherapy-naïve CRPC cases treated with first-line ARAT were analyzed. Outcome measures were PSA response, PSA progression-free survival (PSA-PFS), time to treatment failure (TTF), cancer specific survival (CSS) and overall survival (OS). Results Abiraterone (A) and enzalutamide (E) were administered to 61 and 181 patients, respectively. The median PSA response rate (−65.4% [A] and −78.8% [E], p = 0.0341), PSA decline ≥ 30% (55.7% [A] and 72.9% [E], p=0.0183), PSA-PFS (median 4 months [A] and 8 months [E], p=0.021), TTF (median 6 months [A] and 14 months [E], p<0.0001), CSS (median 45 months [A] and not reached [E], p < 0.0001) and OS (median 28 months [A] and 80 months [E], p=0.00029) were significantly better in the enzalutamide group. In the multivariate analyses for CSS and OS, ALP (p=0.003763) and ARAT (p=0.0002052) (CSS), evidence of metastasis (p=0.04674), Hb (p=0.00205) and ARAT (p=0.005143) (OS) were significant factors, respectively. Conclusion This study showed that PSA response, PSA-PFS, TTF, CSS and OS were better with first-line enzalutamide administration. Direct inhibition of androgen receptor signaling by enzalutamide is associated with better clinical outcomes.