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

Abstract

BackgroundEnzalutamide, 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-naïve metastatic castration-resistant prostate cancer. ObjectiveTo assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. Design, setting, and participantsOne 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). InterventionOral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy. Outcome measurements and statistical analysisCoprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. Results and limitationsEnzalutamide 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. ConclusionsEnzalutamide provided clinically significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. Patient summaryPatients 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.