Efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) in men with de novo (M1) metastatic hormonesensitive prostate cancer (mHSPC) versus progression to mHSPC (M0): Post hoc analysis of the phase III ARCHES trial.

Background: In ARCHES (NCT02677896) ENZA + ADT reduced the risk of radiographic progression-free survival (rPFS) events, primary endpoint, and improved key secondary endpoints vs PBO + ADT in men with mHSPC (also known as metastatic castration-sensitive PC). Given the progressive nature of PC, this exploratory analysis evaluated efficacy of ENZA + ADT in patients (pts) who progressed to M1 HSPC following initial diagnosis (M0) vs pts who presented with de novo mHSPC at diagnosis (M1). Method(s): mHSPC pts (n=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel use. In this post hoc analysis, pts previously centrally categorized as MX/unknown metastasis at initial diagnosis (n=213) were adjudicated as either M0 or M1 disease following review of their medical profiles; efficacy outcomes were compared according to M0 vs M1 disease at initial diagnosis. Result(s): In this analysis, 246 pts (ENZA n=117; PBO n=129) had M0 and 890 pts (ENZA n=448; PBO n=442) had M1 disease at initial diagnosis; metastatic status of 14 pts (ENZA n=9; PBO n=5) were unknown (data not shown). Baseline characteristics were generally comparable between treatment arms; however, a greater proportion of M1 pts had high disease volume (n=606; 68.1% vs n=116; 47.2% [M0]) and prior docetaxel (n=173, 19.4% vs n=29, 11.8% [M0]). ENZA + ADT improved rPFS vs PBO + ADT irrespective of M0 or M1 disease at diagnosis; similar improvements were observed for secondary endpoints including prostate-specific antigen (PSA) and objective responses, time to PSA progression, time to new antineoplastic therapy (Table). Safety profiles were generally similar between subgroups and the overall population; exceptions include higher fatigue in M0 ENZA and PBO treatment arms. Conclusion(s): This post hoc analysis demonstrates clinical benefit of ENZA + ADT vs PBO + ADT based on rPFS and secondary endpoints in men who progressed from M0 to M1 HSPC and those with d