Enzalutamide with standard first-line therapy in metastatic prostate cancer

I.D. Davis, A.J. Martin, M.R. Stockler, S. Begbie, K.N. Chi, S. Chowdhury, X. Coskinas, M. Frydenberg, W.E. Hague, L.G. Horvath, A.M. Joshua, N.J. Lawrence, G. Marx, J. McCaffrey, R. McDermott, M. McJannett, S.A. North, F. Parnis, W. Parulekar, D.W. PookM.N. Reaume, S.K. Sandhu, A. Tan, T.H. Tan, A. Thomson, E. Tu, F. Vera-Badillo, S.G. Williams, S. Yip, A.Y. Zhang, R.R. Zielinski, C.J. Sweeney, for the ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group

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250 Citations (Scopus)

Abstract

BACKGROUND Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer. METHODS In this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events. RESULTS A total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P=0.002). Kaplan-Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P<0.001) and in clinical progression-free survival (167 and 320 events, respectively; hazard ratio, 0.40; P<0.001). Treatment discontinuation due to adverse events was more frequent in the enzalutamide group than in the standard-care group (33 events and 14 events, respectively). Fatigue was more common in the enzalutamide group; seizures occurred in 7 patients in the enzalutamide group (1%) and in no patients in the standard-care group. CONCLUSIONS Enzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel.

Original languageEnglish
Pages (from-to)121-131
Number of pages11
JournalThe New England Journal of Medicine
Volume381
Issue number2
DOIs
Publication statusPublished - 11 Jul 2019

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