The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer

Background: Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naive metastatic castration-resistant prostate cancer. Objective: To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. Design, setting, and participants: One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n = 872) or placebo (n = 845). Subgroup analyses included nonvisceral (only bone and/or nodal; n = 1513), visceral (lung and/or liver; n = 204), low-volume bone disease (< 4 bone metastases; n = 867), high-volume bone disease (>= 4 bone metastases; n = 850), lymph node only disease (n = 195). Intervention: Oral enzalutamide (160 mg) or placebo once daily while continuing androgen deprivation therapy. Outcome measurements and statistical analysis: Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. Results and limitations: Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low-or high-volume bone disease (HR, 0.16; 95% CI, 0.11-0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (< 1) across all disease subgroups, although 95% CI was > 1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease. Conclusions: Enzalutamide provided clinically significant benefits in men with chemotherapy-naive metastatic castration-resistant prostate cancer, with or without visceral disease, low-or high-volume bone disease, or lymph node only disease. Patient summary: Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease or widespread bone disease-benefitted from enzalutamide, an active well-tolerated therapy. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.