(UroToday.com) The 2026 American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL, will host the Prostate, Testicular, and Penile Cancer – Posters Session. Dr. Arnulf Stenzl will present Abstract 5092: Efficacy and safety of enzalutamide in patients with mHSPC and cardiometabolic comorbidities and/or related concomitant medications: ARCHES post hoc.
Prior analyses from the phase 3 ARCHES trial demonstrated significant improvements in radiographic progression-free survival and overall survival with enzalutamide plus ADT compared with placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC).1 Given the high prevalence of cardiometabolic diseases (CMDs) in this patient population, this analysis specifically evaluated the efficacy and safety of enzalutamide among patients with underlying CMDs receiving related concomitant medications.
The investigators evaluated two CMD populations within ARCHES: a full CMD cohort, which included patients with CMDs or receiving CMD-related medications, and a confirmed CMD cohort, which required both a documented CMD diagnosis and the use of concomitant CMD-related medications. Cardiometabolic conditions included hypertension, cardiac disorders, dyslipidemia, and diabetes mellitus.
Among the 1,150 patients enrolled in ARCHES, 938 patients (82%) met criteria for the full CMD cohort, while 756 patients (66%) comprised the confirmed CMD population.
In the full CMD cohort, enzalutamide remained associated with significant improvements in radiographic progression-free survival and overall survival compared with placebo, with similar findings observed across sensitivity analyses and concomitant medication subgroups. These benefits were consistent regardless of the specific CMD-related medications being administered.
At the 2021 data cutoff, median treatment duration was substantially longer in the enzalutamide arm compared with placebo (41 months versus 14 months). Importantly, treatment-emergent adverse event rates per 100 patient-years were comparable between enzalutamide and placebo (313.8 versus 468.0, respectively).
Rates of adverse events of special interest with enzalutamide versus placebo included fatigue (14.4 versus 18.0 per 100 patient-years), falls (6.2 versus 2.6), fractures (7.3 versus 5.4), select cardiovascular events (2.5 versus 1.6), and convulsions (0.2 versus 0.5). No new safety signals were identified.
Key messages:
- Enzalutamide maintained significant efficacy in patients with mHSPC and underlying cardiometabolic diseases
- Improvements in radiographic progression-free survival and overall survival were consistent across CMD-related subgroups and sensitivity analyses
- Treatment-emergent adverse event rates were comparable between enzalutamide and placebo when adjusted for exposure
- No new safety signals were identified among patients with cardiometabolic comorbidities receiving concomitant medications
- These findings support enzalutamide as an effective frontline treatment option for patients with mHSPC regardless of underlying cardiometabolic disease status
Presented by: Arnulf Stenzl, MD, University Hospital Tubingen, Tubingen, Germany
Written by: Julian Chavarriaga, MD, Clinical Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health @chavarriagaj on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026
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