TY - JOUR
T1 - Enzalutamide in metastatic prostate cancer before chemotherapy
AU - PREVAIL Investigators
AU - Beer, Tomasz M
AU - Armstrong, Andrew J
AU - Rathkopf, Dana E
AU - Loriot, Yohann
AU - Sternberg, Cora N
AU - Higano, Celestia S
AU - Iversen, Peter
AU - Bhattacharya, Suman
AU - Carles, Joan
AU - Chowdhury, Simon
AU - Davis, Ian D
AU - de Bono, Johann S
AU - Evans, Christopher P
AU - Fizazi, Karim
AU - Joshua, Anthony M
AU - Kim, Choung-Soo
AU - Kimura, Go
AU - Mainwaring, Paul
AU - Mansbach, Harry
AU - Miller, Kurt
AU - Noonberg, Sarah B
AU - Perabo, Frank
AU - Phung, De
AU - Saad, Fred
AU - Scher, Howard I
AU - Taplin, Mary-Ellen
AU - Venner, Peter M
AU - Tombal, Bertrand
AU - Hoskin, Peter
PY - 2014/7/31
Y1 - 2014/7/31
N2 - BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy.METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival.RESULTS: The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment.CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.).
AB - BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy.METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression-free survival and overall survival.RESULTS: The study was stopped after a planned interim analysis, conducted when 540 deaths had been reported, showed a benefit of the active treatment. The rate of radiographic progression-free survival at 12 months was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo (81% risk reduction; hazard ratio in the enzalutamide group, 0.19; 95% confidence interval [CI], 0.15 to 0.23; P<0.001). A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; P<0.001). The benefit of enzalutamide was shown with respect to all secondary end points, including the time until the initiation of cytotoxic chemotherapy (hazard ratio, 0.35), the time until the first skeletal-related event (hazard ratio, 0.72), a complete or partial soft-tissue response (59% vs. 5%), the time until prostate-specific antigen (PSA) progression (hazard ratio, 0.17), and a rate of decline of at least 50% in PSA (78% vs. 3%) (P<0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment.CONCLUSIONS: Enzalutamide significantly decreased the risk of radiographic progression and death and delayed the initiation of chemotherapy in men with metastatic prostate cancer. (Funded by Medivation and Astellas Pharma; PREVAIL ClinicalTrials.gov number, NCT01212991.).
KW - Adenocarcinoma/drug therapy
KW - Administration, Oral
KW - Androgen Receptor Antagonists/adverse effects
KW - Antineoplastic Agents, Hormonal/adverse effects
KW - Disease Progression
KW - Double-Blind Method
KW - Humans
KW - Male
KW - Neoplasm Metastasis/diagnostic imaging
KW - Phenylthiohydantoin/adverse effects
KW - Prostatic Neoplasms/drug therapy
KW - Radiography
KW - Receptors, Androgen
KW - Survival Analysis
U2 - 10.1056/NEJMoa1405095
DO - 10.1056/NEJMoa1405095
M3 - Article
C2 - 24881730
SN - 1533-4406
VL - 371
SP - 424
EP - 433
JO - The New England Journal of Medicine
JF - The New England Journal of Medicine
IS - 5
ER -
