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 eitherenzalutamide (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.).
RCT Entities:
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.).
Authors: Howard I Scher; Karim Fizazi; Fred Saad; Mary-Ellen Taplin; Cora N Sternberg; Kurt Miller; Ronald de Wit; Peter Mulders; Kim N Chi; Neal D Shore; Andrew J Armstrong; Thomas W Flaig; Aude Fléchon; Paul Mainwaring; Mark Fleming; John D Hainsworth; Mohammad Hirmand; Bryan Selby; Lynn Seely; Johann S de Bono Journal: N Engl J Med Date: 2012-08-15 Impact factor: 91.245
Authors: Johann Sebastian de Bono; Stephane Oudard; Mustafa Ozguroglu; Steinbjørn Hansen; Jean-Pascal Machiels; Ivo Kocak; Gwenaëlle Gravis; Istvan Bodrogi; Mary J Mackenzie; Liji Shen; Martin Roessner; Sunil Gupta; A Oliver Sartor Journal: Lancet Date: 2010-10-02 Impact factor: 79.321
Authors: Chris Tran; Samedy Ouk; Nicola J Clegg; Yu Chen; Philip A Watson; Vivek Arora; John Wongvipat; Peter M Smith-Jones; Dongwon Yoo; Andrew Kwon; Teresa Wasielewska; Derek Welsbie; Charlie Degui Chen; Celestia S Higano; Tomasz M Beer; David T Hung; Howard I Scher; Michael E Jung; Charles L Sawyers Journal: Science Date: 2009-04-09 Impact factor: 47.728
Authors: Ian F Tannock; Ronald de Wit; William R Berry; Jozsef Horti; Anna Pluzanska; Kim N Chi; Stephane Oudard; Christine Théodore; Nicholas D James; Ingela Turesson; Mark A Rosenthal; Mario A Eisenberger Journal: N Engl J Med Date: 2004-10-07 Impact factor: 91.245
Authors: Charlie D Chen; Derek S Welsbie; Chris Tran; Sung Hee Baek; Randy Chen; Robert Vessella; Michael G Rosenfeld; Charles L Sawyers Journal: Nat Med Date: 2003-12-21 Impact factor: 53.440
Authors: Howard I Scher; Susan Halabi; Ian Tannock; Michael Morris; Cora N Sternberg; Michael A Carducci; Mario A Eisenberger; Celestia Higano; Glenn J Bubley; Robert Dreicer; Daniel Petrylak; Philip Kantoff; Ethan Basch; William Kevin Kelly; William D Figg; Eric J Small; Tomasz M Beer; George Wilding; Alison Martin; Maha Hussain Journal: J Clin Oncol Date: 2008-03-01 Impact factor: 44.544
Authors: A Pfestroff; M Luster; C A Jilg; P J Olbert; C H Ohlmann; M Lassmann; H R Maecke; S Ezziddin; L Bodei Journal: Eur J Nucl Med Mol Imaging Date: 2015-12 Impact factor: 9.236
Authors: Christian Daniel Fankhauser; Cédric Poyet; Stephanie G C Kroeze; Benedikt Kranzbühler; Helena I Garcia Schüler; Matthias Guckenberger; Philipp A Kaufmann; Thomas Hermanns; Irene A Burger Journal: World J Urol Date: 2018-07-20 Impact factor: 4.226
Authors: Daniel M Moreira; Lauren E Howard; Katharine N Sourbeer; Hiruni S Amarasekara; Lydia C Chow; Dillon C Cockrell; Connor L Pratson; Brian T Hanyok; William J Aronson; Christopher J Kane; Martha K Terris; Christopher L Amling; Matthew R Cooperberg; Stephen J Freedland Journal: Clin Genitourin Cancer Date: 2016-08-31 Impact factor: 2.872
Authors: Joe-Elie Salem; Tao Yang; Javid J Moslehi; Xavier Waintraub; Estelle Gandjbakhch; Anne Bachelot; Francoise Hidden-Lucet; Jean-Sebastien Hulot; Bjorn C Knollmann; Benedicte Lebrun-Vignes; Christian Funck-Brentano; Andrew M Glazer; Dan M Roden Journal: Circulation Date: 2019-08-05 Impact factor: 29.690