Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer

Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, castration-resistant prostate cancer and rapidly increasing prostate-specific antigen (PSA) levels while taking androgen-deprivation therapy. Results from the final analysis of overall survival have not yet been reported.

In this double-blind, phase 3 trial, men with nonmetastatic, castration-resistant prostate cancer (defined on the basis of conventional imaging and a PSA doubling time of ≤10 months) who were continuing to receive androgen-deprivation therapy were randomly assigned (in a 2:1 ratio) to receive enzalutamide at a dose of 160 mg or placebo once daily. Overall survival was assessed with a group sequential testing procedure and an O’Brien–Fleming–type alpha-spending function.

As of October 15, 2019, a total of 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died. Median overall survival was 67.0 months (95% confidence interval [CI], 64.0 to not reached) in the enzalutamide group and 56.3 months (95% CI, 54.4 to 63.0) in the placebo group (hazard ratio for death, 0.73; 95% CI, 0.61 to 0.89; P=0.001). The exposure-adjusted rate of adverse events of grade 3 or higher was 17 per 100 patient-years in the enzalutamide group and 20 per 100 patient-years in the placebo group. Adverse events in the enzalutamide group were consistent with those previously reported for enzalutamide; the most frequently reported events were fatigue and musculoskeletal events.

Enzalutamide plus androgen-deprivation therapy resulted in longer median overall survival than placebo plus androgen-deprivation therapy among men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level. The risk of death associated with enzalutamide was 27% lower than with placebo. Adverse events were consistent with the established safety profile of enzalutamide. (Funded by Pfizer and Astellas Pharma; PROSPER ClinicalTrials.gov number, NCT02003924.)

Authors: Cora N. Sternberg, M.D., Karim Fizazi, M.D., Ph.D., Fred Saad, M.D., Neal D. Shore, M.D., Ugo De Giorgi, M.D., Ph.D., David F. Penson, M.D., M.P.H., Ubirajara Ferreira, M.D., Ph.D., Eleni Efstathiou, M.D., Ph.D., Katarzyna Madziarska, M.D., Ph.D., Michael P. Kolinsky, M.D., Daniel I. G. Cubero, M.D., Ph.D., Bettina Noerby, M.D., Fabian Zohren, M.D., Ph.D., Xun Lin, Ph.D., Katharina Modelska, M.D., Ph.D., Jennifer Sugg, M.S., Joyce Steinberg, M.D., and Maha Hussain, M.D., for the PROSPER Investigators*

Source: Sternberg, C., Fizazi, K., Saad, F., Shore, N., De Giorgi, U., & Penson, D. et al. (2020). Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. New England Journal Of Medicine. doi: 10.1056/nejmoa2003892

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