ORLANDO, FL, USA (UroToday.com) - In 2010, the U.S. Food and Drug Administration issued an official warning notice regarding evidence for cardiovascular toxicity with the use of LHRH agents as androgen deprivation therapy (ADT) for men with hormone-sensitive prostate cancer.^[1]

Results from a 2014 pooled analysis of 6 randomized, controlled phase III trials provided more specific guidance, stating that GnRH antagonists “…appear to halve the number of cardiac events experienced by men with preexisting cardiovascular disease during the first year of ADT, when compared to GnRH agonists.”^[2]

Against this historical backdrop, German investigators reporting at the 2015 ASCO Genitourinary Cancers Symposium presented results from a large, multiyear retrospective analysis of German health insurance data that also revealed trends related to treatment with ADT vs: no ADT; CV disease and advanced age; CV disease and prostate cancer; and gaps in coordinated care in a setting of need for both urological and cardiovascular follow-up.^[3]  Christoph Russel from the Center for Urology in Borken, Germany described an examination of German Statutory Health Insurance (SHI) data from the years 2009-2012. In a database search, the investigators identified 44 166 men with prostate cancer, of whom 10 611 were treated with ADT. The majority, 10 554, received a GnRH agonist. Only 132 were treated with a GnRH antagonist.^[3]

Although the investigators reported “a clearly increased occurrence of 'serious cardiovascular events'" (i.e., acute coronary syndrome (ACS) and ischemia stroke) among prostate cancer patients as a whole, the CV event rate in the ADT group, at 7.8%, exceeded that of the group of patients who did not receive ADT, at 5.9%.  The investigators noted an increased prevalence of “relevant baseline CV diseases” among ADT-treated patients vs a non-prostate cancer reference group: diabetes mellitus (28.66% vs 17.43%; CAD (335.77% vs 15.70%); heart failure (27.54% vs 9.64%).

However, the risk of serious adverse CV events varied depending on the choice of ADT. In the small group of patients receiving a GnRH antagonist (degarelix), the CV event rate was low, at 2.3%, and all events occurred among patients with a high-risk profile.

But there were qualifiers. Almost 100% of patients receiving ADT were above what investigators referred to as the “critical age limit” of 60 years at the time of a CV event.

Because of the frequent coincident presence of urologic and cardiovascular disease states, Russel et al. evaluated the coordination of care among treating specialists. Their finding was that, in German clinical settings, “…urologists are already important partners in the detection and observation of cardiovascular comorbidity.” Vigilance from the cardiologists’ standpoint was far short of ideal. The rate of cardiological concomitant treatment of ADT patients, they found, “… was not even 30% (28.8%).”

While the trends reported in this analysis were based on the experience from a single nation, the message appears universally relevant that a coordination between general practitioner, cardiologist, and urologist should be maintained in the setting where androgen deprivation therapy is prescribed for the treatment of prostate cancer.

References:

1. FDA.gov. FDA Drug Safety Communication: Update to Ongoing Safety Review of GnRH Agonists and Notification to Manufacturers of GnRH Agonists to Add New Safety Information to Labeling Regarding Increased Risk of Diabetes and Certain Cardiovascular Diseases. At: http://www.fda.gov/Drugs/DrugSafety/ucm229986.htm
2. Albertsen PC, et al. Cardiovascular morbidity associated with gonadotropin-releasing hormone agonists and an antagonist. Eur Urol. 2014;65:565-573.
3. Russel C., Androgen deprivation therapy and cardiovascular risk. At: http://meetinglibrary.asco.org/content/106160?format=posterImg

Presented at the 2015 Genitourinary Cancers Symposium - "Integrating Biology Into Patient-Centric Care" - February 26 - 28, 2015 - Rosen Shingle Creek - Orlando, Florida USA