Eugene B. Cone, MD, a urologic oncology fellow at Brigham and Women’s Hospital and Massachusetts General Hospital, discusses research investigating the cardiac toxicity of gonadotropin-releasing hormone (GnRH) agonists and antagonists in prostate cancer.

It’s common for patients with prostate cancer to develop biochemical recurrence or present with advanced disease, says Cone. Frontline treatments commonly include GnRH agonists such as leuprolide, or GnRH antagonists such as degarelix (Firmagon). Both agents have similar clinical benefits and clinical profiles; however, the cardiac toxicity associated with these drugs has not been well established.

To that end, investigators evaluated the cardiac toxicities of these agents through pharmacovigilance methodologies, which have not historically been used in urology, says Cone. In the analysis, investigators pooled data from VigiBase, which is a database from the World Health Organization. The database compiles reports from more than 130 countries across the globe. The data were used to determine the relative cardiac risk with GnRH agonist and antagonist therapy.

Videos

Dr. Cone on Research Investigating Cardiac Toxicity of GnRH Agonists/Antagonists in Prostate Cancer

Eugene B. Cone, MD, a urologic oncology fellow at Brigham and Women’s Hospital and Massachusetts General Hospital, discusses the methods that were used to evaluate the relative cardiac risk of gonadotropin-releasing hormone (GnRH) agonists versus antagonists in patients with prostate cancer.

Investigators pooled information from VigiBase, which is a database from the World Health Organization that accumulates reports from over 130 countries. In order to perform a propensity-based analysis, investigators compiled the number of patients who received these drugs and reported the number of adverse events (AEs) associated with their use; that number served as the denominator. Then, investigators examined the number of patients who took these drugs and experienced cardiac AEs.

To determine what the expected count should be, investigators took everyone who received any other drug in the database, from aspirin to chemotherapy, and experienced any AE. Then, investigators looked at the number of patients who took any other drug and had a cardiac AE to see what the expected event rate would be. Finally, investigators compared the two rates and determined whether there was a signal or not with GnRH agonists and antagonists.

Dr. Cone on Evaluating the Relative Cardiac Risk of GnRH Agonists Versus Antagonists in Prostate Cancer

Eugene B. Cone, MD, urologist, Massachusetts General Hospital, discusses the cardiac toxicity associated with gonadotropin-releasing hormone (GnRH) agonists in prostate cancer.

GnRH agonists and antagonists are used in the treatment of patients with advanced prostate cancer; however, the relative risk of cardiac toxicity is not well defined, says Cone. Using VigiBase, the World Health Organization’s global database of case safety reports, investigators identified cardiac-related adverse events that were associated with the GnRH antagonist degarelix (Firmagon) and the GnRH agonists, leuprolide, goserelin, triptorelin, and histrelin.

The analysis showed that GnRH agonists have a significantly worse risk of cardiac toxicity compared with GnRH antagonists. These data suggest that a patient with biochemical recurrence who has had a heart attack should receive a GnRH antagonist opposed to a GnRH agonist, says Cone. Although the data are less clear regarding men with other comorbidities, GnRH antagonists are believed to be the preferred drug class, concludes Cone.

Eugene B. Cone, MD

Articles

Dr. Cone on Research Investigating Cardiac Toxicity of GnRH Agonists/Antagonists in Prostate Cancer

Dr. Cone on Evaluating the Relative Cardiac Risk of GnRH Agonists Versus Antagonists in Prostate Cancer

Dr. Cone on Cardiac Toxicity With GnRH Agonists in Prostate Cancer