ARCHES - The role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormonesensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups.

Background: ENZA, a potent androgen receptor inhibitor, provides benefit in men with castration-resistant prostate cancer (CRPC). In post hoc analyses, the role of ENZA+ ADT inmHSPC patients (pts) randomized within the multinational, doubleblind, PBO-controlled, Phase 3 ARCHES study (NCT02677896) was determined by disease volume and risk group stratification. Method(s): mHSPC pts were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints included prostate-specific antigen (PSA) progression and radiographic responses, overall survival (OS), and quality of life (QoL). Analyses were completed by CHAARTED-defined disease volume and LATITUDE-defined risk groups. Result(s): 1150 pts were randomized (ENZA +ADT, n=574; PBO +ADT, n=576). Median follow-up was 14.4 months. ENZA + ADT significantly improved rPFS (hazard ratio [95% CI] 0.39 [0.30, 0.50]; p<0.0001). ENZA+ ADT pts significantly benefited from prolonged rPFS in all subgroups (Table). Significant treatment benefits were observed with ENZA + ADT in several secondary clinical endpoints in the overall population and in both high and low disease volume and risk groups (Table). High QoL at baseline was maintained over time. OS data are immature. Adverse events (AEs) were reported in 85.1% of ENZA + ADT vs. 85.9% of PBO +ADT pts, with no unexpected AEs. Conclusion(s): ENZA+ ADT treatment showed efficacy benefit across all mHSPC pts, irrespective of disease volume and risk group. Similar delays in rPFS, symptomatic skeletal events, PSA progression, castration resistance, and improvements in radiographic responses and PSA declines, with maintenance of high QoL over time, were observed. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials.