Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial.
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Date
2017-10-01ICR Author
Author
Alumkal, JJ
Chowdhury, S
Loriot, Y
Sternberg, CN
de Bono, JS
Tombal, B
Carles, J
Flaig, TW
Dorff, TB
Phung, D
Forer, D
Noonberg, SB
Mansbach, H
Beer, TM
Higano, CS
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Liver Neoplasms
Lung Neoplasms
Phenylthiohydantoin
Prognosis
Treatment Outcome
Administration, Oral
Double-Blind Method
Aged
Aged, 80 and over
Male
Prostatic Neoplasms, Castration-Resistant
Research team
Prostate Cancer Targeted Therapy Group
Language
eng
Date accepted
2017-02-19
License start date
2017-10
Citation
Clinical genitourinary cancer, 2017, 15 (5), pp. 610 - 617.e3
Publisher
CIG MEDIA GROUP, LP