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:
Financial disclosures: Christopher P. Evans certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Evans has served as a consultant for and received research funding from Medivation, Astellas, Sanofi, and Janssen. Higano has served as a consultant for Astellas, Bayer, Dendreon, Johnson & Johnson, and Medivation, and has received research funding from Algeta, Aragon, Astellas, Dendreon, Medivation, and Sanofi. Keane has received fees from Algeta, Dendreon, Ferring, Janssen, and Medivation. Andriole has served as a consultant for Augmenix, Bayer, Genomic Health, GlaxoSmithKline, and Myriad Genetics, and as an investigator for Johnson & Johnson, Medivation, and Wilex. Saad has served as a consultant for and received research funding from Astellas, Janssen, Bayer, Sanofi, Amgen, and Takeda. Iversen has served as a consultant for Astellas, Ferring, Janssen, and Medivation, and has received research funding from Astellas, Bavarian Nordic, and Medivation. Miller has served as a consultant and/or on speaker's bureaus for Astellas, Amgen, Janssen-Cilag, Medivation, Novartis, Pierre-Fabre, and Roche. Kimura has received honoraria and/or clinical study fees from Astellas, Bayer, GlaxoSmithKline, Novartis, Ono Pharmaceutical, Pfizer, Janssen, and Takeda. Armstrong has served as a consultant for and his institution has received research support from Astellas, Bayer, Dendreon, Janssen, Medivation, and Sanofi Aventis; he has served on a speaker's bureau for Dendreon and on advisory boards for Janssen, Medivation/Astellas, Bayer. Sternberg has served as a consultant for and her institution has received research support from Astellas, Bayer, Ipsen, Janssen, Sanofi Aventis, and Millennium. Loriot has received research funding from Astellas and Sanofi, and personal fees from Astellas, Bayer, Celgene, Janssen, and Sanofi. de Bono has served as a consultant for Astellas, AstraZeneca, Johnson & Johnson, Medivation, and Sanofi. Noonberg, Mansbach, and Bhattacharya are employees of Medivation. Perabo was an employee of Astellas at time of study design, conduct, and analysis. Beer has served as a consultant for Astellas and Janssen Japan, and has received research funding from Astellas, Janssen, and Medivation. Tombal has served as a consultant and/or on boards and speaker's bureaus for Amgen, Astellas, Bayer, Ferring, Medivation, and Sanofi, and has received research funding from Astellas.
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
UR - http://www.scopus.com/inward/citedby.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
VL - 70
SP - 675
EP - 683
JO - European Urology
JF - European Urology
SN - 0302-2838
IS - 4
ER -