CUA 2017: Early Cardiovascular Morbidity in a Pilot Prospective Randomized Trial Comparing Luteinizing Hormone-Releasing Hormone Agonist and Antagonist Among Patients with Advanced Prostate Cancer

Toronto, Ontario ( Dr. Jehonathan Pinthus from McMaster University and colleagues presented their results of cardiovascular morbidity in a pilot study comparing luteinizing hormone-releasing hormone (LHRH) agonist and LHRH antagonist use at the CUA 2017 prostate cancer poster session.

There has been much debate regarding the potential increased cardiovascular risk for patients on androgen deprivation therapy (ADT), although it is generally accepted that LHRH antagonists may be associated with lower cardiovascular events compared to men receiving LHRH agonists.The purpose of this trial was to assess the impact of LHRH agonist vs antagonist on cardiovascular event rate, and the potential role of follicle-stimulating hormone (FSH) in mediating ADT-induced atherosclerosis.  

In this pilot clinical trial, a randomized, open-label study compared the use of LHRH antagonist degarelix to LHRH agonists for men with prostate cancer and pre-existing cardiovascular disease. Men were set to be starting ADT for at least one year. Cardiovascular events were considered a composite primary outcome of myocardial infarction, ischemic or hemorrhagic cerebrovascular event, arterial embolic and thrombotic events, emergency room visit or hospitalization due to ischemic heart disease (IHD), or coronary artery or peripheral vascular disease event (vascular surgery/intervention). Serum levels of FSH were taken at baseline and every three months. Enrolment included 66 patients randomized 1:1 to each arm with a median follow-up of 8.5 months. There was no difference between the groups with regards to age, stage of prostate cancer or baseline cardiovascular disease. During follow-up, 12 patients developed a new cardiovascular event, including four patients hospitalized due to IHD, one patient suffering a myocardial infarction, and one patient having a new ischemic cerebrovascular event. Of the 12 patients, 10 experiencing the primary outcome were randomized to the LHRH agonist arm. FSH levels decreased from pre-ADT levels by a median of 92% for men in the degarelix arm compared to only 25% reduction in the LHRH agonist arm (p=0.0001). 

Results from this pilot study suggest that cardiovascular events may develop early in patients with pre-existing cardiovascular disease receiving an LHRH agonist compared to an LHRH antagonist. Interestingly, these events may secondary to poor suppression of FSH. We eagerly await the results of the larger clinical trial. 

Presented By: Jehonathan H. Pinthus, MD, PhD, McMaster University, Hamilton, ON, Canada

Co-Authors: Avivit Pe'er, Yaara Ber, Marina Shaparberg, Rachel Ozalvo, Jack Baniel, Wilhelmina Duivenvoorden, David Margel

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre  Twitter: @zklaassen_md at the  72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada