Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial.
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.



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.



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.



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.
OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR. Electronic address: alumkalj@ohsu.edu.
Joshi J
JJ
Alumkal
Department of Medical Oncology, Guy's Hospital, London, UK.
Simon
S
Chowdhury
Department of Cancer Medicine, Gustave Roussy, University of Paris-Sud, Villejuif, France.
Yohann
Y
Loriot
Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
Cora N
CN
Sternberg
Division of Clinical Studies, Royal Marsden Hospital and Institute of Cancer Research, London, UK.
Johann S
JS
de Bono
Department of Urology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Bertrand
B
Tombal
Department of Medical Oncology, Vall d'Hebron University Hospital, and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Joan
J
Carles
Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
Thomas W
TW
Flaig
Department of Medical Oncology, USC Norris Cancer Hospital, Keck Medical Center of USC, Los Angeles, CA.
Tanya B
TB
Dorff
Department of Biostatistics, Astellas Pharma Europe, BV, Leiden, Netherlands.
De
Phung
Department of Biostatistics, Medivation, Inc, San Francisco, CA.
David
D
Forer
Department of Clinical Development, Medivation, Inc, San Francisco, CA.
Sarah B
SB
Noonberg
Department of Clinical Development, Medivation, Inc, San Francisco, CA.
Hank
H
Mansbach
OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, OR.
Tomasz M
TM
Beer
Division of Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA.
Celestia S
CS
Higano
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D004311:Double-Blind Method; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000556:secondary; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D016896:Treatment Outcome
D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide
Androgen receptor inhibitor; Chemotherapy-naive; Metastases; Phase III; Survival analysis