TY - JOUR
T1 - Enzalutamide with standard first-line therapy in metastatic prostate cancer
AU - Davis, I.D.
AU - Martin, A.J.
AU - Stockler, M.R.
AU - Begbie, S.
AU - Chi, K.N.
AU - Chowdhury, S.
AU - Coskinas, X.
AU - Frydenberg, M.
AU - Hague, W.E.
AU - Horvath, L.G.
AU - Joshua, A.M.
AU - Lawrence, N.J.
AU - Marx, G.
AU - McCaffrey, J.
AU - McDermott, R.
AU - McJannett, M.
AU - North, S.A.
AU - Parnis, F.
AU - Parulekar, W.
AU - Pook, D.W.
AU - Reaume, M.N.
AU - Sandhu, S.K.
AU - Tan, A.
AU - Tan, T.H.
AU - Thomson, A.
AU - Tu, E.
AU - Vera-Badillo, F.
AU - Williams, S.G.
AU - Yip, S.
AU - Zhang, A.Y.
AU - Zielinski, R.R.
AU - Sweeney, C.J.
AU - for the ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
PY - 2019/7/11
Y1 - 2019/7/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85068561926&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa1903835
DO - 10.1056/NEJMoa1903835
M3 - Article
C2 - 31157964
SN - 0028-4793
VL - 381
SP - 121
EP - 131
JO - The New England Journal of Medicine
JF - The New England Journal of Medicine
IS - 2
ER -