Enzalutamide monotherapy: Extended follow-up of a phase II study in hormone-naive prostate cancer patients.

Abstract

62 Background: The efficacy and safety of enzalutamide (ENZA) monotherapy was assessed in hormone-naive men with prostate cancer (PC; any stage) eligible for androgen-deprivation therapy (ADT). The primary end point of prostate-specific antigen (PSA) response rate (80% or more decline), assessed at 25 weeks (wks), was 92.5% with a median (range) maximum decrease of –99% (–100, –86.5) (Tombal et al. ASCO-GU 2013). Here we present data from the extended follow-up at 49 wks. Methods: In an open-label, single-arm phase II study, men age 18 or older with histologically confirmed PC requiring ADT, non-castrate testosterone (8 nmol/L or more), PSA 2 ng/mL or more at screening and a life expectancy of 12 months or more, received 160 mg ENZA once daily (NCT01302041). Treatment continued until disease progression or unacceptable toxicity. Secondary end points included changes in endocrine levels, metabolic parameters, bone mineral density (BMD), quality of life, and safety. Results: Sixty seven men were enrolled. Median (range) age was 73 (48 to 86); 38.8% had prior metastases; 35.8% and 23.94% had undergone prior prostatectomy and radiotherapy, respectively. Fifty nine men continued treatment beyond wk 25, and 54 completed wk 49. PSA response rate (80% or more reduction from baseline) at wk 49 was 80.6%, with a median (range) maximum decrease of –100% (–100, –86.5). Luteinizing hormone and testosterone were increased from baseline to wk 49 by 215.2% and 101.7%, respectively. Mean changes from baseline for metabolic outcomes at wk 49 were: +5.02% (total cholesterol), +8.86% (triglycerides), –3.54% (HbA1c), and +19.72% (HOMA-IR). Total body BMD was maintained at 49 wks (–0.30% from baseline). The most frequently reported treatment-emergent adverse events (AEs) were gynecomastia (47.8%) and fatigue (38.8%). Seven men had serious AEs, none of which were drug related. Data on patient reported outcomes will be presented. Conclusions: ENZA monotherapy was associated with significant PSA reductions after 49 wks of treatment in men with hormone-naive PC. Endocrine changes and AEs were consistent with potent AR inhibition. Outcomes for all end points at 49 wks were consistent with those reported at 25 wks. Clinical trial information: NCT01302041.