Background: In the PREVAIL study, enzalutamide was demonstrated to be effective in men with chemo-naïve metastatic castration-resistant prostate cancer (CRPC). In Japan, enzalutamide was introduced in 2014. Real-world evidence is needed for the long-term safety and efficacy of enzalutamide. The aim of this study was to evaluate the efficacy, safety and prognostic factors in CRPC treated with enzalutamide. Methods: This multicenter, prospective, observational study enrolled 163 Japanese CRPC patients between January 2016 and March 2019. Eligibility criteria were men with chemo-naïve CRPC, no prior treatment with novel androgen receptor signaling inhibitors, and an ECOG- Performance Status ≤ 2. The switching of bicalutamide and flutamide was eligible. Written consent for participation has been obtained from the patient. Enzalutamide 160 mg/day was administered once daily according to usual practice. Data were collected from medical records at baseline and every 3 months until march 2021. The primary endpoint was overall survival (OS), and factors associated with OS were examined. Cox proportional hazards model was used for statistics. The secondary endpoints were PSA response and safety. Results: At a median follow-up of 26.0 months, the median OS was 42.1 months and 24-month OS rate was 69%. Univariate analysis showed that time to CRPC, pretreatment serum PSA, baseline NSE, and baseline interleukin-6 (IL-6) levels were associated with OS. Multivariate analysis revealed that pretreatment serum PSA (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.30-4.10), baseline NSE (HR 2.97, 95%CI 1.24-7.11), and baseline IL-6 (HR 2.32 95%CI 1.32-4.09) were independent risk factors for OS. PSA decline more than 50% was 74% (n=120). Fatigue (30%, n=49), constipation (20%, n=32) and appetite loss (18%, n=29) were the most common adverse events (AEs). Dose reduction/drug discontinuation rates were 20% (n=33) due to AEs and 18% (n=29) due to patient request. Conclusions: The efficacy and safety of enzalutamide in Japanese real clinical practice were comparable to those reported in PREVAIL study. The present analysis also suggests that serum PSA, NSE and IL-6 levels are independent prognostic factors in CRPC patients. Clinical trial information: UMIN000019855.

^aHazard ratio [95% CI], p value.