Joshi J Alumkal1, Simon Chowdhury2, Yohann Loriot3, Cora N Sternberg4, Johann S de Bono5, Bertrand Tombal6, Joan Carles7, Thomas W Flaig8, Tanya B Dorff9, David Forer10, Sarah B Noonberg11, Hank Mansbach11, Tomasz M Beer12, Celestia S Higano13. 1. OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR. Electronic address: alumkalj@ohsu.edu. 2. Department of Medical Oncology, Guy's Hospital, London, UK. 3. Department of Cancer Medicine, Gustave Roussy, University of Paris-Sud, Villejuif, France. 4. Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy. 5. Division of Clinical Studies, Royal Marsden Hospital and Institute of Cancer Research, London, UK. 6. Department of Urology, Cliniques universitaires Saint-Luc, Brussels, Belgium. 7. Department of Medical Oncology, Vall d'Hebron University Hospital, and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. 8. Department of Medicine, University of Colorado School of Medicine, Aurora, CO. 9. Department of Medical Oncology, USC Norris Cancer Hospital, Keck Medical Center of USC, Los Angeles, CA. 10. Department of Biostatistics, Medivation, Inc, San Francisco, CA. 11. Department of Clinical Development, Medivation, Inc, San Francisco, CA. 12. OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR. 13. Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA.
Abstract
BACKGROUND: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have FailedAndrogen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy. PATIENTS AND METHODS: Prespecified analyses examined the coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) only. All other efficacy analyses were post hoc. The visceral subgroup was divided into liver or lung subsets. Patients with both liver and lung metastases were included in the liver subset. RESULTS: Of the 1717 patients in PREVAIL, 204 (12%) had visceral metastases at screening (liver only or liver/lung metastases, n = 74; lung only metastases, n = 130). In patients with liver metastases, enzalutamide was associated with an improvement in rPFS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.90) but not OS (HR, 1.04; 95% CI, 0.57-1.87). In patients with lung metastases only, the HR for rPFS (0.14; 95% CI, 0.06-0.36) and the HR for OS (0.59; 95% CI, 0.33-1.06) favored enzalutamide over placebo. Patients with liver metastases had worse outcomes than those with lung metastases, regardless of treatment. Enzalutamide was well tolerated in patients with visceral disease. CONCLUSIONS:Enzalutamide is an active first-line treatment option for men with asymptomatic or mildly symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer and visceral disease. Patients with lung-only disease fared better than patients with liver disease, regardless of treatment.
RCT Entities:
BACKGROUND: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy. PATIENTS AND METHODS: Prespecified analyses examined the coprimary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) only. All other efficacy analyses were post hoc. The visceral subgroup was divided into liver or lung subsets. Patients with both liver and lung metastases were included in the liver subset. RESULTS: Of the 1717 patients in PREVAIL, 204 (12%) had visceral metastases at screening (liver only or liver/lung metastases, n = 74; lung only metastases, n = 130). In patients with liver metastases, enzalutamide was associated with an improvement in rPFS (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22-0.90) but not OS (HR, 1.04; 95% CI, 0.57-1.87). In patients with lung metastases only, the HR for rPFS (0.14; 95% CI, 0.06-0.36) and the HR for OS (0.59; 95% CI, 0.33-1.06) favored enzalutamide over placebo. Patients with liver metastases had worse outcomes than those with lung metastases, regardless of treatment. Enzalutamide was well tolerated in patients with visceral disease. CONCLUSIONS:Enzalutamide is an active first-line treatment option for men with asymptomatic or mildly symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer and visceral disease. Patients with lung-only disease fared better than patients with liver disease, regardless of treatment.