KEY TAKEAWAYS
- Researchers examined real-world data to contrast cardiovascular events (MACE) and mortality risk in prostate cancer patients using LHRH Agonists versus GNRH Antagonists.
- In the first 4 ADT years, GnRH antagonists in PCa patients showed higher MACE and mortality than LHRH agonists, emphasizing the need for close monitoring and comorbidity treatment.
Gonadotropin-releasing hormone (GnRH) antagonists, presumed to reduce major adverse cardiovascular events (MACE) by avoiding follicle-stimulating hormone (FSH) flare, demonstrated lower MACE rates than leuprolide in the HERO trial.
In the PRONOUNCE trial, investigators found no MACE difference between degarelix and leuprolide. A meta-analysis revealed that antagonist use correlated with reduced overall mortality (Risk Ratio=0.48, 95% CI 0.26-0.90, p=0.02).
For this study, researchers aimed to analyze the real-world data of MACE and mortality risk, acknowledging potential variations from clinical trials due to patient selection. They evaluated the cardiovascular and mortality outcomes of LHRH agonists versus antagonists in prostate cancer patients.
They conducted data analyses on the data from Decision Resources Group, covering the US healthcare system with >300 million patients. The study focused on prostate cancer patients who received at least one ADT injection between 1991-2020, with 99% starting ADT between 2010-2020.
Exclusions comprised patients using both agonists and antagonists and those with MACE <6 months before ADT. MACE included myocardial infarction, stroke, and all-cause mortality. Comparative analysis used Kaplan-Meier curves and Cox regression, factoring in variables linked to increased MACE risk.
The cohort had a median age of 75, with 12.7% Black and 1.3% Asian patients. MACE history distribution was similar between agonist and antagonist groups (3.0% vs. 3.4%). Post-ADT initiation, MACE occurred in 7,681 patients, with incidences of 3.9% and 19.6% at 1 and 4 years. MACE rates varied among racial groups.
Antagonists showed higher unadjusted (HR=1.5, 95% CI 1.4-1.7, p<0.001) and adjusted (HR=1.6, 95% CI 1.2-2.1, p<0.001) incidences compared to agonists. Mortality risk at 1 and 4 years post-ADT initiation was 2.6% and 17%, respectively, with higher unadjusted (HR=1.6, 95% CI 1.4-1.8, p<0.001) and adjusted (HR=1.8, 95% CI 1.3-2.4, p<0.001) risks for antagonists over agonists.
The analysis showed MACE and mortality risk consistently rose by 4-5% annually in the initial 4 years post-ADT initiation. PCa patients on GnRH antagonists had higher MACE and mortality than LHRH agonists. When the data from ~45,000 patients was analyzed over a decade, researchers found that it mirrors real-world outcomes.
Considering the elevated burden of under-assessed CV risk factors in ADT initiation, clinicians should prioritize monitoring and treating comorbidities. Given conflicting data from prospective trials, comprehensive studies are essential to understanding time trends, predictive CV risk factors, and MACE mechanisms.
Source: https://suo-abstracts.secure-platform.com/a/gallery/rounds/18/details/2875
Dorff, T., et al. Real-World Analyses of MACE and Mortality Risk in Patients with Prostate Cancer After Initiation of LHRH Agonists vs. GnRH Antagonist. Presented at: 2023 Society of Urologic Oncology Annual Meeting. November 28 – December 1, 2023; Washington, DC. Abstract 42.
