Christopher P Evans1, Celestia S Higano2, Thomas Keane3, Gerald Andriole4, Fred Saad5, Peter Iversen6, Kurt Miller7, Choung-Soo Kim8, Go Kimura9, Andrew J Armstrong10, Cora N Sternberg11, Yohann Loriot12, Johann de Bono13, Sarah B Noonberg14, Hank Mansbach15, Suman Bhattacharya16, Frank Perabo17, Tomasz M Beer18, Bertrand Tombal19. 1. Department of Urology, UC Davis Comprehensive Cancer Center, Sacramento, CA, USA. Electronic address: cpevans@ucdavis.edu. 2. Medical Oncology Division, University of Washington/Seattle Cancer Care Alliance, Seattle, WA, USA. 3. Department of Urology, Medical University of South Carolina, Charleston, SC, USA. 4. Division of Urologic Surgery, Washington University School of Medicine, St. Louis, MO, USA. 5. Department of Surgery, University of Montreal Health Center, Montreal, Canada. 6. Copenhagen Prostate Cancer Center, Rigshospitalet, University of Copenhagen, Denmark. 7. Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 8. Department of Urology, Asan Medical Center, Seoul, South Korea. 9. Department of Urology, Nippon Medical School Hospital, Tokyo, Japan. 10. Division of Medical Oncology and Urology, Duke Cancer Institute, Durham, NC, USA. 11. Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy. 12. Department of Cancer Medicine, Institut Gustave-Roussy, Villejuif, France. 13. Drug Development Unit, Institute of Cancer Research, Royal Marsden Hospital, London, UK. 14. Department of Early Clinical Development, Medivation, Inc., San Francisco, CA, USA. 15. Department of Medical Affairs, Medivation, Inc., San Francisco, CA, USA. 16. Department of Biostatistics, Medivation, Inc., San Francisco, CA, USA. 17. Astellas Pharma, Inc., Northbrook, IL, USA. 18. Department of Hematology and Medical Oncology, OHSU Knight Cancer Institute, Portland, OR, USA. 19. Department of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Abstract
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-naïve 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 (160mg) 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-naïve 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.
RCT Entities:
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-naïve 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 (160mg) 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-naïve 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.
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