Data Supporting the Risk of MACEs in ADT

Transcript:

Susan F. Slovin, MD, PhD: Given the preponderance of adverse effects, you can see that the patient may have 1 or many, and it can affect their overall quality of life and their performance status. Most of the data, as I alluded to before, regarding cardiovascular changes, date back to several studies. Several studies evaluated the role of intermittent androgen deprivation in patients who have metastatic disease or had newly diagnosed metastatic disease. And about anywhere from 23% to 35% indicated that men seemed to have a greater risk, or worsening, of their pre-existing cardiovascular events. And that included hypertension, stroke, myocardial infarction, and even changes in cholesterol.

This subsequently led to a variety of other studies that were largely, again, retrospective. People just looked at the data and found there was a correlation between adverse effects and the presence of androgen deprivation therapy, such that the European medical agencies actually put the hold on using androgen deprivation therapy, period and exclamation, because everybody said, “Oh my goodness, this can’t be happening.”

And what they did was mandate that any person or any company that is dispensing androgen deprivation therapy analog indicate that there is a much greater risk of cardiovascular events that can occur as a result.

This actually also led to a similar report and subsequent hold by our FDA, and this is about 2010, when a paper came out, which was a multidisciplinary paper that involved the American College of Cardiology, the American Neurological Association, and the American Heart Association. So several agencies were sent back and looked at published reports, again, retrospectively, where they were able to substantiate that there was a very high risk of cardiovascular disease. And as such, leuprolide, for example; goserelin acetate, or Zoladex, all had in their patient insert, and it remains in the package inserts that these drugs are at high risk for major cardiovascular events.

For some reason it doesn’t seem to be translated into practical care. While it is in the package insert, somehow the information—with Lupron or Zoladex, for example—that is given to patients, I don’t think that many urologists or even medical oncologists make patients aware of these concerns.

This again became a major point of exploration when Anthony D’Amico and his group at Brigham and Women’s Hospital a number of years ago presented, again, retrospective data in patients who were treated with hormones and radiation, and again they found a very substantial risk to patients who had pre-existing cardiovascular disease. In fact, that risk could start as early as 3 to 6 months after initiating therapy. So we’re changing obviously the entire cardiovascular environment.

Now there are patients who have just baseline hypertension or diabetes, and of course we always feel that these are patients who are best served by being followed by their primary care physicians or internists. But where we get into some really major concerns is when we ask, How severe is severe? And how do we go about really circumventing the development of these issues?

Well, most of the data that are out there have been—again, as I’ve alluded to multiple times—retrospective; they’re not prospective. Dr Nancy Keating in multiple papers has really brought to light the fact that in looking at different patient populations, duration of treatment, and depth of prior interventions with medical therapy, this is still a widespread problem with the use of androgen deprivation therapy.

Transcript Edited for Clarity