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N Engl J Med. 2012 Sep 27;367(13):1187-97. Epub 2012 Aug 15.

Increased survival with enzalutamide in prostate cancer after chemotherapy.

Collaborators (144)

Alasino C, Bella S, Carraro S, Geist M, Abdi E, Begbie S, Briscoe K, Davis I, Dowling A, Ganju V, Gurney H, Hovey E, Ng S, Nottage M, Rosenthal M, Stockler M, Tan T, Wong S, Young R, Krainer M, Loidl W, Machiels J, Mebis J, Renard V, Dumez H, Van Aelst F, Werbrouck P, Ellard S, Joshua A, Karakiewicz P, Lacombe L, Lattouf JB, Michels J, Mukherjee S, Ruether D, Venner P, Winquist E, Wood L, Aren O, Gonzalez P, Pastor P, Baumgaertner I, Beuzeboc P, Bompas E, Boyle H, Colombel M, Delva R, Eymard J, Gravis G, Guillot A, Houédé N, Joly F, Kaphan R, Loriot Y, Oudard S, Priou F, Tartas S, Theodore C, Tourani JM, Voog E, Bögemann M, Hadaschik B, Hammerer P, Heidenreich A, Holzer W, Merseburger A, Stenzl A, Steuber T, Suttmann H, Trojan L, Wirth M, Cerbone L, Conte P, Passalacqua R, Tucci M, Gerritsen W, Jassem J, Kalinka-Warzocha E, Olubiec J, De Bruyne R, Malan J, Vorobiof D, Bellmunt J, Carles J, Durán I, Font A, Gil-Bazo I, Maroto J, Bahl A, Choudhury A, Hoskin P, James N, Jones R, Mazhar D, O'Sullivan J, Payne H, Pedley I, Protheroe A, Waxman J, Zivi A, Alexander B, Appleman L, Aragon-Ching J, Arrowsmith E, Assikis V, Beer T, Berry W, Bolger G, Bryce A, Bubley G, Chatta G, Denmeade S, Deshpande H, Dorff T, Galsky M, George D, Giudice R, Glode M, Golshayan AR, Goodman O, Graff J, Green L, Green R, Haas N, Higano C, Hutson T, Kohli M, Liu G, May J, Mendelson D, Picus J, Pili R, Posadas E, Redfern C, Rettig M, Ryan C, Scholz M, Sharifi N, Sosman J, Srinivas S, Tagawa S, Twardowski P, Vaishampayan U, Wong YN.

Author information

1
Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065, USA. scherh@mskcc.org

Abstract

BACKGROUND:

Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy.

METHODS:

In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity. We randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). The primary end point was overall survival.

RESULTS:

The study was stopped after a planned interim analysis at the time of 520 deaths. The median overall survival was 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) in the enzalutamide group versus 13.6 months (95% CI, 11.3 to 15.8) in the placebo group (hazard ratio for death in the enzalutamide group, 0.63; 95% CI, 0.53 to 0.75; P<0.001). The superiority of enzalutamide over placebo was shown with respect to all secondary end points: the proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more (54% vs. 2%, P<0.001), the soft-tissue response rate (29% vs. 4%, P<0.001), the quality-of-life response rate (43% vs. 18%, P<0.001), the time to PSA progression (8.3 vs. 3.0 months; hazard ratio, 0.25; P<0.001), radiographic progression-free survival (8.3 vs. 2.9 months; hazard ratio, 0.40; P<0.001), and the time to the first skeletal-related event (16.7 vs. 13.3 months; hazard ratio, 0.69; P<0.001). Rates of fatigue, diarrhea, and hot flashes were higher in the enzalutamide group. Seizures were reported in five patients (0.6%) receiving enzalutamide.

CONCLUSIONS:

Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. (Funded by Medivation and Astellas Pharma Global Development; AFFIRM ClinicalTrials.gov number, NCT00974311.).

PMID:
22894553
DOI:
10.1056/NEJMoa1207506
[Indexed for MEDLINE]
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