Cardiac Toxicity in Nonmetastatic CRPC

Transcript: Judd Moul, MD: Before we move on from the topic of nonmetastatic CRPC [castration-resistant prostate cancer], I want to bring up the final issue of cardiovascular toxicity. To my knowledge, apalutamide has not been associated with any cardiac toxicity in this space, but there are some slight concerns about enzalutamide. Recently, I saw an epidemiological study demonstrating that abiraterone may be associated with further cardiac toxicity in patients who have preexisting cardiac disease. I’ll start with Alicia. Can you make some comments for our audience about cardiac toxicity? Is there any differentiating factor for these agents?

Alicia Morgans, MD, MPH: I think we still need more data. As we continue to use these agents, and as we continue to have registries and postmarketing registries that give us data, that will be helpful. Something Neeraj mentioned that I think about are the drug-drug interactions. Whether it’s direct toxicity or toxicities associated with drug-drug interactions that we may not be aware of or are not able to keep up with, we have the power to watch drug-drug interactions through our specialty pharmacist as we’re prescribing these medications. That is something I would think about.

There are some data to suggest that darolutamide, because of its different structure, may have fewer drug-drug interactions. We also need more data on that, but I’ve seen it, at least in poster form.

That would be helpful to know. We should be very careful, when prescribing these medications, to listen to the specialty pharmacist if he or she says, “Watch this beta-blocker,” or, “Watch this statin,” and make the adjustments that are recommended. I wouldn’t say that I necessarily choose 1 drug over the other for cardiovascular disease. One point I wanted to make is that falls and fractures are still going to be an issue for some of these frailer patients. If there is a patient at very high risk of falls, there’s something on the label noting that enzalutamide is not the best drug to choose in that case. I believe that’s somewhere on the label. That is something I would consider, but for cardiovascular issues, I don’t know that the data are secure enough.

Judd Moul, MD: If you look at the package insert for enzalutamide, there is some labeling language surrounding cardiac toxicity that’s not in the apalutamide label. Tanya or Neeraj, do you want to comment on that?

Neeraj Agarwal, MD: I’ll make a quick comment on that. We have used enzalutamide since 2012 or 2013, right? There is substantial experience with enzalutamide. When these patients start any treatment for M0 [nonmetastatic] CRPC, they have usually been on testosterone suppression therapy for years. By the time they are progressing to M0 CRPC, we have to keep in mind that they are dealing with lack of testosterone in their body for many preceding years. They already have subclinical cardiac adverse effects because of lack of testosterone in their body. I wouldn’t pick up so far based on the data, because they have not been compared with each other.

Judd Moul, MD: Correct.

Neeraj Agarwal, MD: In general, deeper androgen blockade is associated with increased cardiovascular morbidity, whether it is abiraterone, enzalutamide, or other drugs with which we will have long-term experiences down the line. A bigger issue here is that regardless of which drug they are on, it’s very important for us to coordinate with the primary care doctors and make sure they are adequately followed for cardiovascular health. That’s my comment on this.

Judd Moul, MD: Before we leave the topic of nonmetastatic CRPC, I was going to give Tanya the last word. Do you want to make some final comments about your take on the treatment of nonmetastatic CRPC?

Tanya Dorff, MD: Thank you. I do think that not every patient with nonmetastatic CRPC needs 1 of these drugs. I do think it’s very important to check the PSA [prostate-specific antigen] doubling time and to take into account comorbidities and life expectancy. That being said, when I introduce all 3 of these agents—apalutamide, enzalutamide, and soon darolutamide—to my patients who have been on ADT [androgen deprivation therapy] for a long time, I say, “Most of my patients don’t notice a big change in their quality of life when I add this medicine on top of their LHRH [luteinizing hormone-releasing hormone] injection, which we saw from the data sets and I see in my own practice as well.” It’s very important to be good stewards and treat the whole patient, not just the prostate cancer, and make sure—whether it’s through primary care or our own assessments and management—that we take care of their overall health.

Transcript Edited for Clarity