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Enzalutamide in metastatic prostate cancer before chemotherapy

Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E; Loriot, Yohann; Sternberg, Cora N; Higano, Celestia S; Iversen, Peter; Bhattacharya, Suman; Carles, Joan and Chowdhury, Simon, et al. (2014) In New England Journal of Medicine 371(5). p.33-424
Abstract

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... (More)

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.).

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Adenocarcinoma/drug therapy, Administration, Oral, Androgen Receptor Antagonists/adverse effects, Antineoplastic Agents, Hormonal/adverse effects, Disease Progression, Double-Blind Method, Humans, Male, Neoplasm Metastasis/diagnostic imaging, Phenylthiohydantoin/adverse effects, Prostatic Neoplasms/drug therapy, Radiography, Receptors, Androgen, Survival Analysis
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New England Journal of Medicine
volume
371
issue
5
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33 - 424
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Massachusetts Medical Society
external identifiers
  • scopus:84904871070
ISSN
0028-4793
DOI
10.1056/NEJMoa1405095
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English
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2e95258b-cf97-49cc-9fd4-b8d58816b358
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2019-06-28 10:50:39
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2019-08-25 05:17:28
@article{2e95258b-cf97-49cc-9fd4-b8d58816b358,
  abstract     = {<p>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.</p><p>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.</p><p>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&lt;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&lt;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&lt;0.001 for all comparisons). Fatigue and hypertension were the most common clinically relevant adverse events associated with enzalutamide treatment.</p><p>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.).</p>},
  author       = {Beer, Tomasz M and Armstrong, Andrew J and Rathkopf, Dana E and Loriot, Yohann and Sternberg, Cora N and Higano, Celestia S and Iversen, Peter and Bhattacharya, Suman and Carles, Joan and Chowdhury, Simon and Davis, Ian D and de Bono, Johann S and Evans, Christopher P and Fizazi, Karim and Joshua, Anthony M and Kim, Choung-Soo and Kimura, Go and Mainwaring, Paul and Mansbach, Harry and Miller, Kurt and Noonberg, Sarah B and Perabo, Frank and Phung, De and Saad, Fred and Scher, Howard I and Taplin, Mary-Ellen and Venner, Peter M and Tombal, Bertrand and , },
  issn         = {0028-4793},
  keyword      = {Adenocarcinoma/drug therapy,Administration, Oral,Androgen Receptor Antagonists/adverse effects,Antineoplastic Agents, Hormonal/adverse effects,Disease Progression,Double-Blind Method,Humans,Male,Neoplasm Metastasis/diagnostic imaging,Phenylthiohydantoin/adverse effects,Prostatic Neoplasms/drug therapy,Radiography,Receptors, Androgen,Survival Analysis},
  language     = {eng},
  month        = {07},
  number       = {5},
  pages        = {33--424},
  publisher    = {Massachusetts Medical Society},
  series       = {New England Journal of Medicine},
  title        = {Enzalutamide in metastatic prostate cancer before chemotherapy},
  url          = {http://dx.doi.org/10.1056/NEJMoa1405095},
  volume       = {371},
  year         = {2014},
}