Background: ENZA + ADT significantly reduced the risk of radiographic progression or death in men with mHSPC (NCT02677896). Here, we assess how pattern of metastatic spread impacts the efficacy of ENZA + ADT in patients enrolled in ARCHES. Methods: Patients with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or placebo (PBO) + ADT, stratified by disease volume and prior docetaxel treatment. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints included time to prostate-specific antigen (PSA) progression, time to first symptomatic skeletal event (SSE), time to castration resistance, and time to initiation of new antineoplastic therapy. Post hoc analyses were performed by pattern of metastatic spread at study entry. Results: Of the overall population with known metastases at screening (n=1146), the largest patient subgroups were those with bone metastases only (n=513) and those with bone and soft-tissue metastases only (n=351); there were fewer M0 patients or patients with soft-tissue metastases only (n=154) and patients with visceral ± bone metastases (n=128). ENZA + ADT reduced the risk of rPFS and other secondary endpoint measures versus PBO + ADT across all subgroups, with greater relative efficacy observed in patients without visceral metastases (Table). Conclusions: ENZA + ADT provides improvements in rPFS and other secondary endpoints versus PBO + ADT in patients with mHSPC regardless of pattern of metastatic spread, particularly in patients without visceral metastases. These results highlight the importance of patient/physician discussion regarding the use of ENZA in the treatment of mHSPC. Clinical trial information: NCT02677896.

^aAssessed as M0 by independent central review after investigator assessment as M1 at study entry; ^bENZA + ADT; ^cPBO + ADT NE, not estimable; NR, not reached