ASCO 2022: Clinical Outcomes and Safety of Enzalutamide + ADT in mHSPC in Patients Aged 75 and ≥ 75 Years: ARCHES Post Hoc Analysis

(UroToday.com) The 2022 ASCO annual meeting featured a session on prostate cancer, including a presentation by Dr. Russell Szmulewitz discussing a post hoc analysis of ARCHES assessing clinical outcomes and safety of enzalutamide + ADT in mHSPC in patients aged < 75 and ≥ 75 years. Patients with metastatic prostate cancer aged ≥75 years have a poorer prognosis compared with younger patients. For example, overall survival (OS) has been reported at an average of 6.7 months shorter in men aged >=75 years at diagnosis compared with those <=54 years of age. In ARCHES [1], enzalutamide + ADT improved radiographic progression-free survival (rPFS), OS, and other key secondary endpoints versus placebo + ADT in patients with mHSPC. Final OS results confirmed a long-term survival benefit with enzalutamide + ADT. This post hoc analysis of ARCHES data investigated OS and other clinical outcomes in patients aged <75 and ≥75 years.


Patients with mHSPC (n=1,150) were randomized 1:1 to enzalutamide (160 mg/day) + ADT or placebo + ADT, stratified by disease volume and prior docetaxel use. Subgroup analysis was performed in patients aged <75 and ≥75 years. In this analysis, efficacy and safety outcomes were compared across treatment arms stratified by age.

Of the ARCHES population, 339 patients (29.5%) were aged ≥75 years (enzalutamide + ADT, n=170; placebo + ADT, n=169); placebo patients crossing over to enzalutamide were aged: <75 years, n=133; ≥75 years, n=47. Some differences in baseline characteristics were observed between age groups, such as higher prior docetaxel use in patients aged <75 years (enzalutamide + ADT, 21.0%; placebo + ADT, 20.4%) versus those aged ≥75 years (enzalutamide + ADT, 10.6%; placebo + ADT, 11.2%):

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When compared to placebo + ADT, enzalutamide + ADT improved OS and other secondary efficacy endpoints in both age groups without evidence of statistical heterogeneity; however, 95% confidence intervals for OS and rPFS hazard ratios spanned 1 in the older age group:

As follows is the clinical outcomes in patients aged <75 years (ITT population):

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As follows is the clinical outcomes in patients aged >=75 years (ITT population):

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The safety profile of treatment arms was generally similar in both age groups, with a higher incidence of falls, cognitive impairment, and cardiovascular events among elderly patients receiving enzalutamide + ADT versus placebo + ADT.

Dr. Szmulewitz concluded his presentation discussing a post hoc analysis of ARCHES assessing clinical outcomes and safety of enzalutamide + ADT in mHSPC in patients aged < 75 and ≥ 75 years with the following take-home messages:

  • Enzalutamide + ADT provides clinical benefit and is generally well-tolerated in patients with mHSPC aged ≥75 years, although with some differences in treatment-related adverse events and the need for dose interruption/reduction compared to men aged <75 years of age
  • These findings support the therapeutic role of enzalutamide, irrespective of age, in men with mHSPC

Presented by: Russell Z. Szmulewitz, MD, The University of Chicago, Chicago, IL

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022. 

References:

  1. Armstrong AJ, Szmulewitz RZ, Petrylak DP, 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 Nov 10;37(32):2974-2986. 
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