ENZARAD (ANZUP 1303): Phase 3 Trial of Enzalutamide With Androgen Deprivation Therapy and Radiation Therapy in High-Risk Localized or Locally Advanced Prostate Cancer

Background The effects of adding enzalutamide to androgen deprivation therapy (ADT) and radiotherapy for high-risk localized or locally advanced prostate cancer were unknown. Methods Open-label, phase 3 trial of definitive prostate radiotherapy with 24 months of ADT and 1:1 randomization to either enzalutamide (160mg daily for 24 months) or an older nonsteroidal antiandrogen (NSAA) for 6 months. The primary endpoint was metastasis-free survival on conventional imaging (MFS-CI) with computerized tomography and/or 99m Tc-bone scintigraphy. Radiation to pelvic lymph nodes was required for cN1 disease but optional for cN0. Results 802 participants were randomized. After a median follow-up of 92 months, 207 MFS-CI events were reported (98 enzalutamide, 109 NSAA) with 8-year MFS-CI rates 74% vs 72%, hazard ratio [HR] 0.88, 95% confidence interval [CI], 0.67 to 1.15; P =0.34). Prespecified subgroup analyses noted enzalutamide was associated with a possible MFS-CI benefit in the subgroup undergoing planned pelvic nodal radiotherapy, N=324 (HR 0.47, 95% CI: 0.29 to 0.76 P adjusted =0.004). Grade 3-5 adverse events were reported in 185 participants in each arm. Conclusions The use of enzalutamide rather than NSAA in addition to radiotherapy and ADT for 2 years showed no significant MFS-CI or OS improvement at 8 years.