Background: The efficacy and safety of enzalutamide monotherapy was assessed in men with any-stage hormone-naive prostate cancer eligible for androgen-deprivation therapy (ADT). The primary endpoint of PSA response rate (≥80% PSA decrease between baseline and week 25) was 92.5% (Smith M et al, ASCO 2013). The median (range) maximum PSA decline from baseline to week 25 was –99.6% (–100, –86.5). 1-year extended follow-up data are presented. Methods: In an open-label, single-arm Phase 2 study (NCT01302041), men ≥18 years with histologically confirmed prostate cancer requiring ADT, non-castrate testosterone (≥8 nmol/L), PSA ≥2 ng/mL at screening, and a life expectancy of ≥12 months, received 160 mg enzalutamide once daily until disease progression or unacceptable toxicity. Other endpoints included changes in hormone levels, metabolic parameters, BMD, safety, and quality of life (QoL). Results: 67 men were enrolled. Median (range) age was 73 years (48–86); 38.8% had metastases; 35.8% and 23.9% had undergone prior prostatectomy and radiotherapy, respectively. 54 men (80.6%) completed 1 year of treatment with a PSA response rate of 100% and 53 (98.1%) had ≥90% PSA decrease from baseline. The median (range) maximum decline in PSA was –100% (–100, –86.5) from baseline to 1 year. Luteinizing hormone and testosterone were increased from baseline by 215.2% and 101.7%, respectively. Mean changes from baseline for fasting metabolic variables were: +5.0% total cholesterol, +8.9% triglycerides, –3.5% HbA1c, and +19.7% insulin resistance (HOMA-IR). Total body BMD was maintained (–0.3% from baseline). The most frequently reported treatment-emergent AEs were gynecomastia (47.8%) and fatigue (38.8%). Seven non-drug-related serious AEs were reported. Qol scores at 1 year demonstrate maintenance of global health status and a decrease in sexual activity and sexual functioning. Conclusions: Extended follow-up of hormone-naive patients demonstrated sustained PSA reductions up to 1 year of enzalutamide monotherapy. Endocrine and metabolic changes, and AEs were consistent with potent AR inhibition and similar to results reported at 25 weeks. Clinical trial information: NCT01302041.