Overall survival (OS) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated with enzalutamide (ENZA) + androgen deprivation therapy (ADT) by high or low disease volume and progression to mHSPC (M0 at diagnosis) or de novo mHSPC (M1 at diagnosis): Post hoc analysis of the phase 3 ARCHES trial.

Abstract

115 Background: In ARCHES (NCT02677896), ENZA + ADT improved radiographic progression-free survival, OS, and other key secondary endpoints vs placebo (PBO) + ADT for pts with mHSPC (also known as metastatic castration-sensitive prostate cancer). Final OS results confirmed a long-term survival benefit with ENZA + ADT (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.53, 0.81; p<0.0001). We present post hoc analyses of OS by disease volume and progression to M1 HSPC after initial diagnosis with localized disease (M0) or presentation of de novo mHSPC at initial diagnosis (M1). Methods: Pts with mHSPC (N=1150) were randomized 1:1 to ENZA (160 mg/day) + ADT (n=574) or PBO + ADT (n=576), stratified by disease volume and prior docetaxel use. After unblinding, 180 (31.3%) PBO + ADT-treated pts crossed over to open-label ENZA + ADT. High disease volume was defined per CHAARTED criteria. Medical profiles of pts assessed as MX/unknown metastasis at initial diagnosis (n=213) were further reviewed centrally and adjudicated as having either M0 or M1 disease. Median OS and HRs were estimated by Kaplan-Meier methods and Cox proportional hazards, respectively. Results: Median treatment duration was 40.2 months (mo) for ENZA + ADT and 13.8 mo for PBO + ADT. Inclusive of crossover, 401 (69.6%) PBO + ADT pts had subsequent life-prolonging therapy. OS benefits with ENZA + ADT were seen in all disease volume and M0/M1 populations at a similar magnitude to the overall population (Table). Median OS was not reached in most populations except PBO + ADT pts with high disease volume (45.9 mo; 95% CI 40.1, not estimable [NE]) or high disease volume and M1 disease (43.4 mo; 95% CI 36.4, 49.7) and ENZA + ADT pts with high disease volume and M0 disease (54.2 mo; 95% CI 54.2, NE). Conclusions: Our post hoc analysis demonstrates consistent long-term survival benefit with ENZA + ADT vs PBO + ADT across pts with mHSPC with high and low disease volumes and M0 or M1 disease at initial diagnosis, despite substantial treatment crossover and subsequent therapy use in PBO + ADT pts.[Table: see text]

Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update

“…13 Enzalutamide also has long-term survival benefits overall, for those with LVD or HVD, and those with LVD or HVD and no docetaxel use. 4 Per ARCHES, 5 enzalutamide significantly improved time to first subsequent antineoplastic therapy in addition to survival benefits overall and among those with HVD, no prior docetaxel and previous use of ADT or orchiectomy 5 (Type: Evidence-based, benefits outweigh harms; Evidence quality: High; Strength of recommendation: Strong).…”

“…The third reason for a focused recommendation update was updated results from two enzalutamide trials (ENZAMET 4 and ARCHES 5 ). The ENZAMET trial released (in abstract form only) updated survival results for patients with metastatic noncastrate prostate cancer after three additional years of follow-up.…”

“…The related ARCHES 5 trial published updated radiographic progression-free survival results after a longer period of follow-up and also reported results for the trial's secondary outcome, overall survival (OS) for patients with metastatic noncastrate prostate cancer, primarily those with de novo metastatic disease. This study compared enzalutamide plus ADT versus placebo plus ADT, stratified by disease volume and prior docetaxel use (sequential treatment).…”

Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update: ASCO Guideline Q and A

“…The results of the ENZAMET 5 and ARCHES 6 trials did not change the 2021 recommendation for enzalutamide other than reporting long-term results from these trials that were not available in 2021. 7…”

“…5 Enzalutamide also has long-term survival benefits overall, for those with LVD or HVD, and those with LVD or HVD and no docetaxel use. 8 Per ARCHES, 6 enzalutamide significantly improved time to first subsequent antineoplastic therapy in addition to survival benefits overall and among those with HVD, no prior docetaxel and previous use of ADT or orchiectomy. effects (alopecia, nausea, fatigue, neutropenia, and peripheral neuropathy), and cost, both drug price and outof-pocket costs.…”