Enzalutamide in metastatic prostate cancer before chemotherapy Journal Article
| Authors: | Beer, T. 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, C. 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. |
| Article 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. Copyright © 2014 Massachusetts Medical Society. |
| Keywords: | cancer survival; survival analysis; survival rate; major clinical study; overall survival; constipation; fatigue; placebo; diarrhea; drug efficacy; drug safety; hypertension; treatment duration; adenocarcinoma; prostate specific antigen; progression free survival; quality of life; cancer mortality; docetaxel; arthralgia; asthenia; backache; prostate cancer; prostatic neoplasms; acute kidney failure; disease progression; cerebrovascular disease; drug response; neoplasm metastasis; peripheral edema; hot flush; antineoplastic agents, hormonal; receptors, androgen; risk reduction; double-blind method; administration, oral; heart atrium fibrillation; phenylthiohydantoin; abiraterone; decreased appetite; acute coronary syndrome; androgen receptor antagonists; enzalutamide; humans; human; male; priority journal; article |
| Journal Title: | New England Journal of Medicine |
| Volume: | 371 |
| Issue: | 5 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2014-07-31 |
| Start Page: | 424 |
| End Page: | 433 |
| Language: | English |
| DOI: | 10.1056/NEJMoa1405095 |
| PUBMED: | 24881730 |
| PROVIDER: | scopus |
| PMCID: | PMC4418931 |
| DOI/URL: | |
| Notes: | Cited By (since 1996):5 -- Export Date: 2 September 2014 -- CODEN: NEJMA -- Source: Scopus |
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