AUA 2022: Overall Survival in Patients with Metastatic Hormone-Sensitive Prostate Cancer Treated with Enzalutamide or Placebo Plus Androgen Deprivation Therapy Who Had Prior Local Therapy: Post Hoc Analysis of the Phase 3 ARCHES Trial

(UroToday.com) In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Iguchi presented a post hoc analysis of the ARCHES trial assessing the effect of prior local therapy on the efficacy of enzalutamide in combination with androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Overall, ARCHES (NCT02677896) demonstrated that enzalutamide and ADT improved radiographic progression-free survival and key secondary endpoints compared to placebo with ADT for patients mHSPC, also known as metastatic castration-sensitive prostate cancer, irrespective of prior local treatment. Subsequently, ongoing follow-up demonstrated a long-term overall survival benefit with enzalutamide plus ADT in the overall study population (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.53, 0.81; p<0.0001).


While previously reported, to briefly summarize, ARCHES enrolled 1150 patients with mHSPC and randomized them in a 1:1 fashion to enzalutamide (160 mg/day)+ADT (n=574) or PBO+ADT (n=576), stratified by disease volume and prior docetaxel use. After unblinding at the time of primary outcome reporting, 180 (31.3%) placebo plus ADT‒treated patients crossed over to receive open-label enzalutamide plus ADT. Median OS and HRs were estimated by Kaplan-Meier methods and Cox proportional hazards, respectively. In this report, the authors focus on subgroup analysis among patients with prior local therapy, defined as previous radical prostatectomy (RP) and/or radiation therapy (RT) to the prostate area (definitive, adjuvant, or salvage) along with analyses stratified by type of prior local therapy (RP, RT, and type of RT).

The median duration of treatment was 40.2 months in patients receiving enzalutamide and ADT, 13.8 months in those receiving placebo and ADT, and 23.9 months in those patients who crossed over to enzalutamide and ADT. The median follow-up time was 44.6 months and, during this time, 401 (69.9%) patients initially randomized to placebo received a subsequent life-prolonging therapy, including cross-over to enzalutamide.

Prior local therapy was reported in 118 patients randomized to enzalutamide (45 RP, 46 RT, 27 both) and 122 randomized to placebo (50 RP, 33 RT, 39 both). of these, 21 (17.8%) and 33 (27.0%) died, respectively. In this subset of the overall cohort, enzalutamide plus ADT reduced the risk of death by 46% vs. placebo plus ADT (HR 0.54; 95% CI 0.31, 0.94), consistent with the overall study population. Median OS was not reached for either arm.

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Other key endpoints including radiographic progression-free survival, time to PSA progression, castration resistance, first symptomatic skeletal related event, first new antineoplastic therapy, and deterioration of urinary symptoms similarly demonstrated a consistent benefit of enzalutamide plus ADT.

Thus, Dr. Iguchi concludes that this post hoc analysis of the ARCHES trial demonstrates the long-term survival benefit of enzalutamide in addition to ADT in patients with mHSPC who received prior local therapy, despite substantial treatment crossover and subsequent therapy use.

Presented by: Taro Iguchi, MD, Department of Urology Kanazawa Medical University Kahoku Ishikawa Japan.

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.

 

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