Background: In ARCHES (NCT02677896), ENZA + ADT reduced the risk of radiographic progression and improved secondary clinical outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) with variable patterns of disease spread over placebo (PBO) + ADT. This post hoc analysis aimed to evaluate the efficacy of ENZA + ADT in patients with bone oligometastatic mHSPC compared to polymetastatic mHSPC in ARCHES. Methods: Patients with mHSPC (n = 1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel chemotherapy. This post hoc analysis included patients with bone metastases only, categorized as oligometastatic (1–≤5 metastases) or as polymetastatic (≥6 metastases) based on central review at screening. Efficacy outcomes were compared across treatment arms. Results: Of the ARCHES population with bone metastases (n = 512), the largest subgroup included patients with ≤5 metastases (ENZA + ADT, n = 160; PBO + ADT, n = 136). Baseline characteristics were generally comparable between treatment arms and across subgroups. When compared to PBO + ADT, ENZA + ADT improved rPFS and secondary endpoints in patients with ≤5 metastases (Table). Similar results were observed across other oligometastatic subgroups (1–≤4) as well as in polymetastatic disease (≥6). The safety profile of ENZA + ADT versus PBO + ADT was similar across subgroups and consistent with previous findings. Conclusions: This post hoc analysis demonstrates that ENZA + ADT provides clinical benefit across bone oligometastatic as well as polymetastatic mHSPC, supporting the utility of ENZA irrespective of metastatic burden in the ARCHES study. Clinical trial information: NCT02677896

^aOligometastatic mHSPC was defined as 1–≤5 bone metastases; polymetastatic mHSPC was defined as ≥6 bone metastases; ^bHR < 1 favors ENZA + ADT; HR > 1 favors PBO + ADT; ^cNumber of patients in subgroup who received ENZA + ADT; ^dNumber of patients in subgroup who received PBO + ADT; ^eAssessed by independent central review, or death, within 24 weeks of treatment discontinuation. CI = confidence interval; HR = hazard ratio; PSA = prostate-specific antigen.