TY - JOUR
T1 - The PREVAIL Study
T2 - Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer
AU - Evans, Christopher P.
AU - Higano, Celestia S.
AU - Keane, Thomas
AU - Andriole, Gerald
AU - Saad, Fred
AU - Iversen, Peter
AU - Miller, Kurt
AU - Kim, Choung Soo
AU - Kimura, Go
AU - Armstrong, Andrew J.
AU - Sternberg, Cora N.
AU - Loriot, Yohann
AU - de Bono, Johann
AU - Noonberg, Sarah B.
AU - Mansbach, Hank
AU - Bhattacharya, Suman
AU - Perabo, Frank
AU - Beer, Tomasz M.
AU - Tombal, Bertrand
N1 - Funding Information:
Funding/Support and role of the sponsor: This study was supported by Medivation, Inc., and Astellas Pharma, Inc. The manuscript was reviewed and comments were provided to the authors by Medivation, Inc., and Astellas Pharma, Inc. Medical writing and editorial support was funded by Medivation, Inc. and Astellas Pharma, Inc., and provided by Tim Lohret, PhD, and Shannon Davis of Infusion Communications.
Publisher Copyright:
© 2016 European Association of Urology
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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 (160 mg) 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.
AB - 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 (160 mg) 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.
KW - Androgen receptor
KW - Castration-resistant prostatic cancer
KW - Enzalutamide
UR - http://www.scopus.com/inward/record.url?scp=84962547110&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2016.03.017
DO - 10.1016/j.eururo.2016.03.017
M3 - Article
C2 - 27006332
AN - SCOPUS:84962547110
SN - 0302-2838
VL - 70
SP - 675
EP - 683
JO - European Urology
JF - European Urology
IS - 4
ER -