Enzalutamide with standard first-line therapy in metastatic prostate cancer

Ian D. Davis*, Andrew J. Martin, Martin R. Stockler, Stephen Begbie, Kim N. Chi, Simon Chowdhury, Xanthi Coskinas, Mark Frydenberg, Wendy E. Hague, Lisa G. Horvath, Anthony M. Joshua, Nicola J. Lawrence, Gavin Marx, John McCaffrey, Ray McDermott, Margaret McJannett, Scott A. North, Francis Parnis, Wendy Parulekar, David W. Pook & 14 others M. Neil Reaume, Shahneen K. Sandhu, Alvin Tan, T. Hsiang Tan, Alastair Thomson, Emily Tu, Francisco Vera-Badillo, Scott G. Williams, Sonia Yip, Alison Y. Zhang, Robert R. Zielinski, Christopher J. Sweeney, ENZAMET Trial Investigators, The Australian and New Zealand Urogenital Prostate Cancer Trials Group (ANZUP)

*Corresponding author for this work

Research output: Contribution to journalArticle

67 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
JournalNew England Journal of Medicine
Volume381
Issue number2
DOIs
Publication statusPublished - 11 Jul 2019

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Davis, I. D., Martin, A. J., Stockler, M. R., Begbie, S., Chi, K. N., Chowdhury, S., ... The Australian and New Zealand Urogenital Prostate Cancer Trials Group (ANZUP) (2019). Enzalutamide with standard first-line therapy in metastatic prostate cancer. New England Journal of Medicine, 381(2), 121-131. https://doi.org/10.1056/NEJMoa1903835