ARCHES: 5-year follow-up overall survival (OS) analysis of enzalutamide (ENZA) plus androgen-deprivation therapy (ADT) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC).

5005 Background: In 2021, final prespecified OS (key secondary endpoint; defined as time from randomization to death from any cause) analysis of the global phase 3, randomized, double-blind, placebo (PBO)-controlled ARCHES trial (NCT02677896) demonstrated that ENZA + ADT significantly reduced risk of death by 34% versus PBO + ADT in pts with mHSPC (medians not reached [NR]; hazard ratio [HR] 0.66; 95% confidence interval [CI]: 0.53–0.81; p<0.0001; median follow-up, 44.6 months). To assess long-term efficacy of ENZA + ADT, we report an updated OS analysis as of July 31, 2024 (median follow-up, 61.4 months). Methods: In ARCHES, 1150 enrolled pts with mHSPC were randomized 1:1 to ENZA (160 mg once daily) + ADT or PBO + ADT. After primary analysis of radiographic progression-free survival (primary endpoint), ARCHES was unblinded to allow eligible patients who were randomized to PBO + ADT to cross over to ENZA + ADT in an open-label extension. Using extended follow-up data with median follow-up >5 years (cut-off date: July 31, 2024), Kaplan–Meier method was used to summarize the OS endpoint by treatment, with two-sided 95% CIs calculated by the Brookmeyer–Crowley method. HRs relative to PBO + ADT were determined using Cox regression model stratified for prior docetaxel use and disease volume. Results: ENZA + ADT (n=574; median [range] age = 70.0 [46–92] years) and PBO + ADT (n=576; median [range] age = 70.0 [42–92] years) cohorts had similar baseline characteristics. 184 (31.9%) PBO + ADT pts crossed over to open-label ENZA + ADT (median [range] age = 69.0 [51–89] years). After a median follow-up of 61.4 months, ENZA + ADT extended survival compared with PBO + ADT (medians NR; HR 0.70; 95% CI: 0.58–0.85; p=0.0003), with consistently improved survival across clinically relevant subgroups analyzed (Table), including a 36-month improvement in median OS in high-volume patients. Conclusions: Long-term follow-up of ARCHES demonstrated results consistent with previous OS analyses, with marked benefit in all study subgroups, including high- and low-volume patients, despite a substantial cross-over cohort. These findings further support ENZA + ADT as a standard-of-care for pts with mHSPC. Clinical trial information: NCT02677896 . Subgroup ENZA + ADTN (events) ENZA + ADT(median months) PBO + ADTN (events) PBO + ADT(median months) HR (95% CI) All 574 (191) NR 576 (223) NR 0.70 (0.58–0.85) Age <65 years 148 (46) 86.4 152 (55) NR 0.63 (0.42–0.93) Age ≥65 years 426 (145) NR 424 (168) NR 0.73 (0.58–0.91) Low-volume disease 220 (50) NR 203 (57) NR 0.71 (0.49–1.05) High-volume disease 354 (141) 83.1 373 (166) 47.6 0.70 (0.56–0.88) No prior docetaxel 471 (157) NR 474 (179) NR 0.71 (0.57–0.88) Prior docetaxel 103 (34) 83.1 102 (44) 59.5 0.67 (0.43–1.05) Synchronous (de novo): ≤90 days 438 (161) 86.4 439 (186) 58.9 0.71 (0.57–0.88) Metachronous (relapsed): >90 days 132 (29) NR 136 (37) NR 0.66 (0.41–1.08)