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ASCO 2019 Annual Meeting

ASCO 2019: Cardiovascular Morbidity in a Randomized Trial Comparing GnRH-Agonist and Antagonist Among Patients with Advanced Prostate Cancer

Chicago, IL (UroToday.com) Androgen-deprivation therapy (ADT) is commonly used to inhibit the progression of advanced prostate cancer. Evidence suggests that the use of ADT is associated with an increase in cardiac-related mortality and diabetes. Limited preclinical and retrospective clinical data suggest that the use of gonadotropin-releasing hormone (GnRH)-antagonist may be associated with a lower risk of cardiovascular disease compared to GnRH-agonist. Furthermore, the men who benefited most were those with pre-existing cardiovascular disease. At the ASCO 2019 prostate cancer session, David Margel, MD, PhD, and colleagues presented results of their study assessing cardiovascular morbidity in a randomized trial comparing GnRH-agonist and antagonist among patients with advanced prostate cancer. Their objectives were to compare endothelial function among prostate cancer patients with pre-existing cardiovascular disease commencing on luteinizing hormone-releasing hormone (LHRH) agonist vs antagonists for 12 months and to compare the new incidence of cardiovascular events. 

This was a randomized open-label study comparing the one-year incidence of major cardiovascular and cerebrovascular events in prostate-cancer patients with pre-existing cardiovascular disease commencing on GnRH-agonists or antagonists. Patients were followed every 3 months for the development of major cardiovascular and cerebrovascular events defined as either death, myocardial infarction, cerebrovascular event, or percutaneous coronary intervention. Endothelial function was measured by EndoPAT200. Serum levels of N-terminal pro-B-type natriuretic peptide were analyzed at baseline, 3-, 6- and 12-months. 

There were 80 patients enrolled: 41 randomized to GnRH-antagonist and 39 to GnRH-agonist. Patients in both arms had similar median age (72 vs 71 years), baseline cardiovascular and prostate-cancer characteristics. During follow-up, 15 patients developed a new cardiovascular event. Of these, nine patients developed major cardiovascular and cerebrovascular events (two deaths, one myocardial infarction, two cerebrovascular events, and four percutaneous-coronary interventions). Twenty percent (n=8) of patients randomized to GnRH-agonists had a major cardiovascular and cerebrovascular event compared to 3% (n=1) randomized to antagonists (log-rank p=0.013). 
ASCO2019_MACCE-freefractionn_FollowUpDays.png
The absolute risk reduction for major cardiovascular and cerebrovascular events at 12 months using GnRH-antagonist was 18% (95%CI 5-31). There was no difference in endothelial function between the two groups. Baseline levels of N-terminal pro-B-type natriuretic peptide predicted events (AUC=0.73 95%CI 0.54-0.91 p=0.03) and increased over time only among patients with cardiovascular events. 

Dr. Margel concluded this study by noting that this is the first prospective study to test cardiovascular outcome among prostate-cancer patients receiving ADT. In patients with pre-existing cardiovascular disease, GnRH-antagonists was associated with the development of fewer cardiovascular events compared to GnRH-agonists. 

Clinical trial information: NCT02475057

Presented by: David Margel, MD, PhD, Rabin Medical Center, Petah Tikva, Israel

Co-Authors: Avivit Peer, Yaara Ber, Sivan Sela, Liat Shavit Grievink, Tzlil Tabachnik, Guy Witberg, Jack Baniel, Daniel Kedar, Wilhelmina CM Duivenvoorden, Eli Rosenbaum, Jehonathan H Pinthus; Rabin Medical Center, Petah Tikva, Israel; Rambam Health Care Campus, Haifa, Israel; Rabin Medical Center, Prtah Tikva, Israel; Tel Aviv University, Tel Aviv, Israel; Rabin Medical Center, Petach Tikvah, Israel; McMaster University, Hamilton, ON, Canada; Davidoff Cancer Center, Petah Tikva, Israel

Written by: Zachary Klaassen, MD, MSc, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA