TY - JOUR
T1 - Effect of Visceral Disease Site on Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Enzalutamide in the PREVAIL Trial
AU - Alumkal, Joshi J.
AU - Chowdhury, Simon
AU - Loriot, Yohann
AU - Sternberg, Cora N.
AU - de Bono, Johann S.
AU - Tombal, Bertrand
AU - Carles, Joan
AU - Flaig, Thomas W.
AU - Dorff, Tanya B.
AU - Phung, De
AU - Forer, David
AU - Noonberg, Sarah B.
AU - Mansbach, Hank
AU - Beer, Tomasz M.
AU - Higano, Celestia S.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - We assessed outcomes from men with metastatic castration-resistant prostate cancer that had spread to the liver and/or lungs in the PREVAIL clinical trial of enzalutamide in patients who had not received docetaxel chemotherapy. Compared with placebo, enzalutamide lengthened the time it took for the cancers to grow (according to changes in scans), prostate-specific antigen to rise, or patients to require chemotherapy. 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.
AB - We assessed outcomes from men with metastatic castration-resistant prostate cancer that had spread to the liver and/or lungs in the PREVAIL clinical trial of enzalutamide in patients who had not received docetaxel chemotherapy. Compared with placebo, enzalutamide lengthened the time it took for the cancers to grow (according to changes in scans), prostate-specific antigen to rise, or patients to require chemotherapy. 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.
KW - Androgen receptor inhibitor
KW - Chemotherapy-naive
KW - Metastases
KW - Phase III
KW - Survival analysis
UR - http://www.scopus.com/inward/record.url?scp=85017112721&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2017.02.007
DO - 10.1016/j.clgc.2017.02.007
M3 - Article
C2 - 28344102
AN - SCOPUS:85017112721
SN - 1558-7673
VL - 15
SP - 610-617.e3
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 5
ER -