ADT and the Risk of Major Adverse Cardiovascular Events - Episode 8

Standard of Care in Metastatic Prostate Cancer


Susan F. Slovin, MD, PhD: The standard of care for patients who have metastatic disease—bone, lymph nodes—has always been using androgen deprivation therapy. When patients are now presenting to clinic with metastatic disease we have 3 new standards of care, if you will. One is standard androgen deprivation, as mentioned, with either a GnRH [gonadotropin-releasing hormone] antagonist or agonist. The second is docetaxel, which is chemotherapy that’s given with androgen deprivation therapy of your choice. The third is using one of the newer androgen receptor signaling inhibitors, abiraterone, along with androgen deprivation therapy. My own treatment choice is really dependent on patient mobility. So, for example, a patient who is in need of treatment but has a hard time coming from wherever they live, so if they’re in the outskirts of New Jersey or Pennsylvania, giving them a depot formulation, such as a GnRH agonist, is very reasonable.

A patient who presents who’s younger, who has an enormous tumor burden, whom I feel has to be treated yesterday, is the first person I would put on a GnRH antagonist.

The mechanism of action of the antagonist usually takes place within 24 to 48 hours. With an agonist it can take up to 10 to 15 days. Hence my own desire to, if I have to really treat somebody, I will use the antagonist much more rapidly. Somebody who needs a more gentle approach, I would use a GnRH agonist.

People often ask me what’s the difference? Well the [adverse] effect profile is the same. It’s really what your preference is or your gestalt of the patient. I use them both equally. The only issue I might have with somebody who needs to have the antagonist is that they may not be able to come back monthly. Ergo I may have to transition them to a 3-month formulation. But they both work very effectively. I can honest say that I don’t see any difference in terms of the [adverse] effect profile, but in an urgent situation where I really feel that treatment is needed, I will use the antagonist.

It’s interesting to note that an abstract just came out that’s going to be presented at the American Association for Cancer Research that now indicates that abiraterone actually is being associated with a greater risk of cardiovascular events being given with a GnRH agonist. So whether, again, this is based on retrospective data. Is it the fact that it’s the agonist or is it that being on abiraterone is making that cardiovascular impact worse remains to be determined. But it’s just interesting that this would be the case now. There are at least 2 papers that have already differed in whether this is true; both were in 2018. One of them indicated that there was definitely a link to increasing cardiovascular risk. The other, just the opposite, and said there was no change whatsoever.

Most of what I’ve mentioned underscores the need for guidelines and a multidisciplinary group in treating patients. All of us as oncologists and neurologists, even radiation oncologists, understand the need for very close monitoring. We always take a medical history. But I don’t think we immediately say we have to send the patient back to their internist or primary care physician, or even cardiologist, to have an assessment of whether it’s safe to give them the GnRH agonist or an antagonist. There’s no data to support that. I think we just do the injection and then we say, “OK, you know, go see your doctor periodically and have your every 6-month or a yearly stress test.”

I think we’re a little negligent. I think we need be to better and establish some form of guidelines that will incorporate the participation more closely of the primary care [physician], cardiologist, or internist.

Now there are recommendations that diet is very important. We always recommend low-fat diets. We recommend that patients monitor their weight. But it gets a little hard sometimes when the agonists or antagonists could put another 5 to 10, or even 15 pounds on a patient. There are recommendations, I don’t know that we would call them official guidelines, but obviously monitoring the triglycerides, the total cholesterol, C-reactive protein, for example, would be very beneficial. But how often to do it and in what scenarios; are there patients for example who are at greater risk for the development of any sort of major cardiovascular events compared with others? Is there an age group that we should be focusing on? That’s not been established to date.

Transcript Edited for Clarity