ARCHES Final OS Analysis in mHSPC

Andrew J. Armstrong, MD, discusses data from the following presentation:

Final overall survival data from the phase 3 randomized, double-blind, placebo-controlled ARCHES study of enzalutamide plus androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer. (Armstrong AJ, et al. ESMO 2021: Abstract LBA25).

• The primary analysis of ARCHES (NCT02677896) showed that enzalutamide plus androgen deprivation therapy (ADT) reduced risk of radiographic progression and improved secondary outcomes in men with metastatic hormone-sensitive prostate cancer (mHSPC) over placebo plus ADT.
  • This study reported the final overall survival (OS), a key secondary end point, which was immature at the time of primary analysis.
• Men with de novo or relapsed mHSPC (n = 1150) were randomized 1:1 to enzalutamide (160 mg per day) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use.
• At the time of data cutoff, 180 (31%) patients treated with placebo plus ADT crossed over to open-label enzalutamide plus ADT.
• Kaplan-Meier estimates of OS and time to subsequent antineoplastic therapy (TTNAnti) were reported. Safety was assessed via treatment-emergent adverse events.
• Efficacy results:
  • Baseline characteristics were similar between treatment arms. As of the data cutoff of May 28, 2021, 397 (35%) patients remained on treatment, with a median follow-up of 44.6 months.
  • Median treatment duration was 40.2 months on enzalutamide plus ADT, 13.8 months on placebo plus ADT, and 23.9 months for crossover patients.
  • Enzalutamide plusADT extended survival vs placebo plus ADT (HR 0.66; 95% confidence interval 0.53, 0.81; P <.0001) with similar results in most prespecified subgroups. Four-year OS rate was 71% in the enzalutamide plus ADT arm vs 57% in the placebo vs ADT arm.
  • Enzalutamide plusADT continued to prolong TTNAnti vs placebo plus ADT. Median TTNAnti was not reached in the enzalutamide-plus-ADT arm vs 40.5 months in the placebo-plus-ADT arm.
• Safety results:
  • The safety profile of enzalutamide plusADT vs placebo plus ADT was consistent with findings from the primary analysis.
• This final analysis demonstrates that enzalutamide plus ADT significantly prolongs survival in men with mHSPC and, together with the acceptable safety profile, supports the clinical benefit of enzalutamide plus ADT in men with mHSPC.