Study assesses cardiovascular effects of ADT in prostate cancer

A recent study conducted by investigators at Emory Winship Cancer Institute found that treatment with androgen deprivation therapy (ADT) led to a rise in the risk of an adverse cardiovascular (CV) event among a significant number of patients with prostate cancer, with those harboring clonal hematopoiesis of indeterminate potential (CHIP) gene variants having an increased odds of experiencing a rise in CV risk.^1,2

Larger studies are underway to assess whether DNMT3A, TET2, and ASXL1 CHIP variants may serve as biomarkers for adverse CV events following treatment with ADT.

The data were presented by Sagar Anil Patel, MD, at the 2024 ASCO Genitourinary Cancers Symposium in San Francisco, California.

“With cancer patients living longer, understanding the adverse cardiac effects due to cancer treatments, such as androgen deprivation therapy (ADT), is critical. We analyzed serial patient blood samples before and at 6-months during androgen deprivation therapy and confirmed a rise, or worsening, in the HART CVE cardiac risk scores in 44% of this patient population,” said Patel in a news release on the findings.² Patel is an assistant professor in the department of radiation oncology and a member of the cancer and control research program at Emory Winship Cancer Institute in Atlanta, Georgia.

Overall, the data showed that among the 25 patients included in the study, 44% experienced a rise in their CV risk from baseline to 6 months following initiation of ADT. Men with increased odds of a CV event were more often Black (72.7% vs 14.3%), on anti-hypertensive medication (72.7% vs 14.3%), and had a higher baseline LDL cholesterol level (median 98 vs 81 mg/dL) compared with men who did not experience a rise in CV risk.

The investigators also assessed the effect of the 3 most common CHIP gene variants (DNMT3A, TET2, ASXL1) on patients’ CV risk. Among the entire cohort, CHIP gene variants were found in 7 (28%) men, 6 (85.7%) of whom were Black men. Even after adjusting for race, anti-hypertensive medication use, and baseline LDL cholesterol levels, patients who harbored at least 1 CHIP variant had an increased odds of an elevated CV risk score following 6 months of ADT (adjusted OR, 1.44; 95% CI, 0.88-1.83). This association did not meet statistical significance; however, the authors noted that the study was limited by the small sample size.

In total, the study included 25 men, 40% of whom were Black. The median patient age was 70 years. Among all patients, 4 (16%) had a history of myocardial infarction. Participants all received radiotherapy plus 6 or more months of ADT with leuprolide.

Peripheral blood samples were measured at baseline and at 6 months following therapy initiation. HART CVE, a 4-protein risk score developed by Provencio, was used to measure the 4-year risk of a major CV event. According to the news release by Provencio,² the HART CVE test has been shown in previous studies to be more accurate (0.86 AUC) at predicting the risk of heart attack, stroke, or cardiac death compared with other single protein blood tests, such as high sensitivity troponin (0.65 AUC), and clinical risk scores (0.57 AUC).

“It is impressive that HART CVE detected increased risk in almost 50% of this cancer treatment population in as little as 6 months and indicates a highly sensitive means of prediction for which patients will have adverse cardiac events from ADT,” said Rhonda Rhyne, president and chief executive officer of Prevencio, in the news release.² “It is rewarding to work with Dr. Patel and his team at Emory Winship Cancer Institute to demonstrate HART CVE’s usefulness in monitoring their prostate cancer patients.”

The authors indicated that larger studies are underway to assess whether DNMT3A, TET2, and ASXL1 CHIP variants may serve as biomarkers for adverse CV events following treatment with ADT, especially among Black men.

References

1. Patel SA, Marra A, Switchenko JM, et al. Clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular toxicity from androgen deprivation therapy in men with prostate cancer. J Clin Oncol 42, 2024 (suppl 4; abstr 312). doi: 10.1200/JCO.2024.42.4_suppl.312

2. Prevencio and Emory Winship Cancer Institute AI-driven HART CVE test data predicts risk of adverse cardiovascular effects associated with prostate cancer therapy. News release. Prevencio, Inc. February 7, 2024. Accessed February 9, 2024. https://www.businesswire.com/news/home/20240207101444/en/Prevencio-and-Emory-Winship-Cancer-Institute-AI-driven-HART-CVE-Test-Data-Predicts-Risk-of-Adverse-Cardiovascular-Effects-Associated-with-Prostate-Cancer-Therapy