(UroToday.com) The 2026 ASCO annual meeting featured a prostate cancer session and a presentation by Dr. Linden Huhmann discussing major adverse cardiovascular events in androgen receptor pathway inhibitor (ARPI)-treated patients with metastatic castration sensitive prostate cancer (mCSPC). Cardiovascular disease is highly prevalent in the predominantly older male population with mCSPC. ARPIs form the backbone of contemporary doublet and triplet treatment strategies, but—as with any systemic therapy—may influence a patient’s underlying cardiovascular risk. This study compares the incidence of major adverse cardiovascular events in real-world mCSPC patients treated with darolutamide versus abiraterone.
This retrospective cohort study included patients in the nationwide VA healthcare system initiating doublet or triplet abiraterone or darolutamide for newly diagnosed mCSPC. After inverse probability of treatment weighting (IPTW), 1-year cumulative major adverse cardiovascular event incidence was estimated via Kaplan-Meier analysis. Doubly robust multivariable Cox regression using IPTW and multivariable competing risk regression with death as a competing risk assessed the association between treatment and major adverse cardiovascular events. All analyses were adjusted for age, race, prior major adverse cardiovascular event, NCI Charlson Score, smoking status, and prior hypertensive combination treatment.
Among 11,788 patients initiating darolutamide or abiraterone for mCSPC, 9,952 received abiraterone doublet, 936 received darolutamide doublet, 374 received abiraterone triplet, and 526 received darolutamide triplet therapy. In the weighted cohort, the 1-year cumulative incidence of major adverse cardiovascular events was lower in patients receiving darolutamide (7.2%, 95% CI 5.6-9.0%) versus abiraterone (10.7%, CI 10.0-11.4%) doublet therapy. For triplet therapy, 1-year major adverse cardiovascular event incidence was 5.3% (CI 3.4-7.4%) with darolutamide and 9.6% (CI 5.9-13.6%) with abiraterone. In doubly robust multivariable Cox models, darolutamide doublet was associated with a lower hazard of major adverse cardiovascular event compared to abiraterone doublet (HR 0.78, CI 0.62-0.96, p = 0.03). For the triplet, patients receiving darolutamide had an HR of 0.73 for major adverse cardiovascular events (CI 0.39-1.31, p = 0.29) compared to patients receiving abiraterone triplet therapy. Competing risk models showed consistent results.
Dr. Huhmann concluded his presentation discussing major adverse cardiovascular events in ARPI-treated patients with mCSPC with the following take-home points:
- Darolutamide, particularly in doublet therapy, was associated with lower major adverse cardiovascular event risk than abiraterone
- A similar point estimate in triplet therapy warrants validation in larger cohorts
- These findings may inform treatment selection or prophylactic management to improve cardiovascular outcomes in mCSPC
Presented by: Linden Huhmann, U.S. Department of Veterans Affairs, Washington, DC
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026