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ARCHES

ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer

Phase 3N = 1,150NCT02677896

Population
Men with metastatic hormone-sensitive prostate cancer
Design
Multinational, double-blind phase 3 trial: 1:1 randomization to enzalutamide 160 mg per day or placebo, plus ADT, stratified by disease volume and prior docetaxel. Primary end point radiographic progression-free survival.
Primary endpoint
rPFS
Arms
  • Placebo plus ADT (control, n = 576): Placebo plus ADT
  • Enzalutamide plus ADT (experimental, n = 574): Enzalutamide 160 mg per day plus ADT
People
Armstrong AJ, ARCHES
rPFSHR 0.39 (95% CI 0.3–0.5)OSHR 0.66 (95% CI 0.53–0.81)
Show the numbers
Results reported for ARCHES
EndpointAnalysisEnzalutamide plus ADTPlacebo plus ADTEffect
rPFSRandomized men (analysis population not stated in the abstract)primaryArmstrong 2019—median 19 monthsHR 0.39 (95% CI 0.3–0.5)P<0.001Median not reached with enzalutamide. Hazard ratio for radiographic progression or death.
OSRandomized men (574 enzalutamide, 576 placebo)finalmedian follow-up 44.6 monthsArmstrong 2022——HR 0.66 (95% CI 0.53–0.81)P<0.001Final prespecified analysis of overall survival, a key secondary end point: 154 deaths with enzalutamide and 202 with placebo; median not reached in either group. After unblinding, 180 progression-free patients (31.3%) assigned to placebo crossed over to enzalutamide.
Results reported for ARCHES
EndpointAnalysisEnzalutamide plus ADTPlacebo plus ADTEffect
rPFSRandomized men (analysis population not stated in the abstract)primaryArmstrong 2019—median 19 monthsHR 0.39 (95% CI 0.3–0.5)P<0.001Median not reached with enzalutamide. Hazard ratio for radiographic progression or death.
OSRandomized men (574 enzalutamide, 576 placebo)finalmedian follow-up 44.6 monthsArmstrong 2022——HR 0.66 (95% CI 0.53–0.81)P<0.001Final prespecified analysis of overall survival, a key secondary end point: 154 deaths with enzalutamide and 202 with placebo; median not reached in either group. After unblinding, 180 progression-free patients (31.3%) assigned to placebo crossed over to enzalutamide.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
rPFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
rPFS0.390.3–0.5
OS0.660.53–0.81
Illustrative — modelled from reported values, not trial data. rPFS, primary.
0%25%50%75%100%010203040Months (modelled)
  • Placebo plus ADT (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsPlacebo plus ADT
0100.0%
1264.5%
2441.7%
3626.9%
4817.4%
Primary publication: Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019;37(32):2974-2986. PubMedDOI

Appears in

Sources

  1. Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019;37(32):2974-2986.

    PubMedDOI

  2. Armstrong AJ, Azad AA, Iguchi T, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, et al. Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2022;40(15):1616-1622.

    PubMedDOI