In ARCHES, androgen deprivation therapy (ADT)+ENZA led to an improved ORR vs ADT+placebo (Pbo) in patients (pts) with mHSPC. Although improvements in ORR indicate short-term clinical benefits, the association between ORR and longer-term benefits has not yet been established. The objective of this post-hoc analysis was to investigate the association between ORR and long-term clinical outcomes in pts with measurable disease who were treated with ENZA. ENZA vs Pbo were compared as an exploratory objective.

This analysis categorized ARCHES pts who had measurable disease at baseline as 1) “responders” (pts with complete response [CR] or partial response [PR]), 2) pts with stable disease (SD), or 3) pts with progressive disease (PD). Primary outcome: 5-year overall survival (OS) in pts treated with ENZA. Secondary outcome: radiographic progression-free survival (rPFS) in pts treated with ENZA. Exploratory endpoints: 5-year OS and rPFS among responders treated with ENZA vs Pbo. The impact of treatment crossover was evaluated as a sensitivity analysis. Associations between response categories and outcomes were analyzed using Pearson’s chi-squared test or Fisher’s exact tests. Time to event outcomes were analyzed using the Kaplan-Meier product limit method.

Among pts treated with ADT+ENZA, responders showed the longest median time from randomization to death from any cause or disease progression (Table). In exploratory analyses of responders only, ENZA was associated with significantly improved 5-year OS and rPFS vs Pbo (Table). Among all pts in the ENZA group, ORR category was significantly associated with 5-year OS (p = 0.01) and rPFS (p < 0.0001). Among pts in the Pbo group, there was no association between ORR category and 5-year OS in primary or sensitivity analyses (p = 0.79 and p = 0.78, respectively).

Among pts treated with ADT+ENZA, responders demonstrated improved 5-year OS and rPFS. In exploratory analyses, responders treated with ADT+ENZA had better long-term clinical outcomes than responders treated with ADT+Pbo. Although some pts in the Pbo group responded to ADT alone, these responses were less durable. Given the post-hoc nature of our analysis and the small sample sizes within each response category, these findings should be interpreted with caution.