ARCHES 5-year Survival with Enzalutamide Plus Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer Patients.

The ARCHES trial (NCT02677896) showed improved radiographic progression-free survival (primary analysis; 2018) and overall survival (prespecified analysis; 2021) with enzalutamide versus placebo, with concomitant androgen-deprivation therapy, in metastatic hormone-sensitive prostate cancer (mHSPC) patients. This post hoc analysis describes 5-yr efficacy and safety for all 1150 randomized patients (data cutoff: July 31, 2024). Patients were randomized 1:1 to receive enzalutamide or placebo (first patient randomized: March 21, 2016). After the primary analysis, ARCHES was unblinded (December 10, 2018); 65% and 32% of patients in the enzalutamide and placebo groups, respectively, enrolled in the open-label extension. After the 61.4-mo median follow-up, 5-yr survival probability was 66% with enzalutamide and 53% with placebo (median months not reached in either group; hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.58, 0.85; p < 0.001; adjusted HR: 0.64; 95% CI: 0.51, 0.75). Patients with high-volume disease who received enzalutamide lived 36 mo longer than those who received placebo (HR: 0.70; 95% CI: 0.56, 0.88). No new safety signals emerged. As this was a post hoc, non-alpha protected analysis, the overall survival p value is nominal and should be interpreted cautiously. Overall, this study provides compelling long-term data demonstrating survival benefits with enzalutamide across diverse patient subgroups to guide clinical decision-making and establish prognostic expectations in the mHSPC setting.