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Enzalutamide in Metastatic Prostate Cancer before Chemotherapy

2014· article· en· 3 031 citations· W2166918329 sur OpenAlex· 10.1056/nejmoa1405095

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Résumé

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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La notice

Revue
New England Journal of Medicine
Thématique
Prostate Cancer Treatment and Research
Domaine
Medicine
Établissements canadiens
University of AlbertaCentre Hospitalier de l’Université de MontréalPrincess Margaret Cancer Centre
Organismes subventionnaires
Cliniques Universitaires Saint-LucNational Cancer InstituteKnight Cancer Institute, Oregon Health and Science UniversityUniversity of California, DavisDuke Cancer InstituteAstellas Pharma Global DevelopmentWeill Cornell Medical CollegeRigshospitaletFundació Institut de Recerca Hospital Universitari Vall d’HebronInstitut Gustave-RoussyAstellas PharmaUniversité de MontréalUniversity of WashingtonUniversity of AlbertaMemorial Sloan-Kettering Cancer CenterMonash UniversityOregon Health and Science University
Mots-clés
EnzalutamideProstate cancerMedicineOncologyChemotherapyInternal medicineDocetaxelCancerAndrogen receptor
Résumé présent dans OpenAlex
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