Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer

Cora N Sternberg, Karim Fizazi, Fred Saad, Neal D Shore, Ugo De Giorgi, David F Penson, Ubirajara Ferreira, Eleni Efstathiou, Katarzyna Madziarska, Michael P Kolinsky, Daniel I G Cubero, Bettina Noerby, Fabian Zohren, Xun Lin, Katharina Modelska, Jennifer Sugg, Joyce Steinberg, Maha Hussain

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.).

Original languageEnglish
Pages (from-to)2197-2206
Number of pages10
JournalThe New England journal of medicine
Volume382
Issue number23
DOIs
Publication statusPublished - Jun 4 2020

Keywords

  • Adenocarcinoma/drug therapy
  • Aged
  • Androgen Antagonists/therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Double-Blind Method
  • Humans
  • Kallikreins/blood
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Phenylthiohydantoin/adverse effects
  • Placebos
  • Prostate-Specific Antigen/blood
  • Prostatic Neoplasms, Castration-Resistant/drug therapy
  • Survival Analysis

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