Enzalutamide in metastatic prostate cancer before chemotherapy

Tomasz M. Beer, A. J. Armstrong, D. E. Rathkopf, Y. Loriot, C. N. Sternberg, C. S. Higano, P. Iversen, S. Bhattacharya, J. Carles, S. Chowdhury, I. D. Davis, J. S. De Bono, Christopher P Evans, K. Fizazi, A. M. Joshua, C. S. Kim, G. Kimura, P. Mainwaring, H. Mansbach, K. MillerS. B. Noonberg, F. Perabo, D. Phung, F. Saad, H. I. Scher, M. E. Taplin, P. M. Venner, B. Tombal

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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 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.

Original languageEnglish (US)
Pages (from-to)424-433
Number of pages10
JournalNew England Journal of Medicine
Volume371
Issue number5
DOIs
StatePublished - 2014

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Prostatic Neoplasms
Drug Therapy
Placebos
Risk Reduction Behavior
Prostate-Specific Antigen
Disease-Free Survival
Confidence Intervals
Survival
MDV 3100
Castration
Androgen Receptors
Therapeutics
Androgens
Fatigue
Hypertension

ASJC Scopus subject areas

  • Medicine(all)

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Beer, T. M., Armstrong, A. J., Rathkopf, D. E., Loriot, Y., Sternberg, C. N., Higano, C. S., ... Tombal, B. (2014). Enzalutamide in metastatic prostate cancer before chemotherapy. New England Journal of Medicine, 371(5), 424-433. https://doi.org/10.1056/NEJMoa1405095

Enzalutamide in metastatic prostate cancer before chemotherapy. / Beer, Tomasz M.; Armstrong, A. J.; Rathkopf, D. E.; Loriot, Y.; Sternberg, C. N.; Higano, C. S.; Iversen, P.; Bhattacharya, S.; Carles, J.; Chowdhury, S.; Davis, I. D.; De Bono, J. S.; Evans, Christopher P; Fizazi, K.; Joshua, A. M.; Kim, C. S.; Kimura, G.; Mainwaring, P.; Mansbach, H.; Miller, K.; Noonberg, S. B.; Perabo, F.; Phung, D.; Saad, F.; Scher, H. I.; Taplin, M. E.; Venner, P. M.; Tombal, B.

In: New England Journal of Medicine, Vol. 371, No. 5, 2014, p. 424-433.

Research output: Contribution to journalArticle

Beer, TM, Armstrong, AJ, Rathkopf, DE, Loriot, Y, Sternberg, CN, Higano, CS, Iversen, P, Bhattacharya, S, Carles, J, Chowdhury, S, Davis, ID, De Bono, JS, Evans, CP, Fizazi, K, Joshua, AM, Kim, CS, Kimura, G, Mainwaring, P, Mansbach, H, Miller, K, Noonberg, SB, Perabo, F, Phung, D, Saad, F, Scher, HI, Taplin, ME, Venner, PM & Tombal, B 2014, 'Enzalutamide in metastatic prostate cancer before chemotherapy', New England Journal of Medicine, vol. 371, no. 5, pp. 424-433. https://doi.org/10.1056/NEJMoa1405095
Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS et al. Enzalutamide in metastatic prostate cancer before chemotherapy. New England Journal of Medicine. 2014;371(5):424-433. https://doi.org/10.1056/NEJMoa1405095
Beer, Tomasz M. ; Armstrong, A. J. ; Rathkopf, D. E. ; Loriot, Y. ; Sternberg, C. N. ; Higano, C. S. ; Iversen, P. ; Bhattacharya, S. ; Carles, J. ; Chowdhury, S. ; Davis, I. D. ; De Bono, J. S. ; Evans, Christopher P ; Fizazi, K. ; Joshua, A. M. ; Kim, C. S. ; Kimura, G. ; Mainwaring, P. ; Mansbach, H. ; Miller, K. ; Noonberg, S. B. ; Perabo, F. ; Phung, D. ; Saad, F. ; Scher, H. I. ; Taplin, M. E. ; Venner, P. M. ; Tombal, B. / Enzalutamide in metastatic prostate cancer before chemotherapy. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 5. pp. 424-433.
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title = "Enzalutamide in metastatic prostate cancer before chemotherapy",
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 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.",
author = "Beer, {Tomasz M.} and Armstrong, {A. J.} and Rathkopf, {D. E.} and Y. Loriot and Sternberg, {C. N.} and Higano, {C. S.} and P. Iversen and S. Bhattacharya and J. Carles and S. Chowdhury and Davis, {I. D.} and {De Bono}, {J. S.} and Evans, {Christopher P} and K. Fizazi and Joshua, {A. M.} and Kim, {C. S.} and G. Kimura and P. Mainwaring and H. Mansbach and K. Miller and Noonberg, {S. B.} and F. Perabo and D. Phung and F. Saad and Scher, {H. I.} and Taplin, {M. E.} and Venner, {P. M.} and B. Tombal",
year = "2014",
doi = "10.1056/NEJMoa1405095",
language = "English (US)",
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TY - JOUR

T1 - Enzalutamide in metastatic prostate cancer before chemotherapy

AU - Beer, Tomasz M.

AU - Armstrong, A. J.

AU - Rathkopf, D. E.

AU - Loriot, Y.

AU - Sternberg, C. N.

AU - Higano, C. S.

AU - Iversen, P.

AU - Bhattacharya, S.

AU - Carles, J.

AU - Chowdhury, S.

AU - Davis, I. D.

AU - De Bono, J. S.

AU - Evans, Christopher P

AU - Fizazi, K.

AU - Joshua, A. M.

AU - Kim, C. S.

AU - Kimura, G.

AU - Mainwaring, P.

AU - Mansbach, H.

AU - Miller, K.

AU - Noonberg, S. B.

AU - Perabo, F.

AU - Phung, D.

AU - Saad, F.

AU - Scher, H. I.

AU - Taplin, M. E.

AU - Venner, P. M.

AU - Tombal, B.

PY - 2014

Y1 - 2014

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.

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.

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