Dr. Crawford on cardiovascular risk with ADT in prostate cancer

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“Where we are with this, I think that our results do not support the theory that agonists have a higher cardiovascular risk than antagonists,” says E. David Crawford, MD.

In this video, E. David Crawford, MD, highlights the background and findings from the study, “Cardiovascular risk in prostate cancer patients using luteinizing hormone-releasing hormone agonists or a gonadotropin-releasing hormone agonist,” for which he served as the lead author. Crawford is a professor of urology at the University of California, San Diego.

Video Transcript:

For decades, we have focused on the [adverse] effects of androgen deprivation therapy, primarily in the hot flashes and to some degree, the effect on bone and osteoporosis. Only recently in the past decade, has it become apparent that there is an increased cardiovascular risk associated with androgen deprivation therapy. When we think about cardiovascular risk, and we think about cancer, they're both chronic diseases, and they have some things in common with our environment, including our weight, blood pressure, diet, and many other things like that. Androgen deprivation therapy just adds another hit, so to speak, to men that have prostate cancer in advanced stages, where we use androgen deprivation therapy. So, there's been a lot of concern about the differences and cardiovascular risks between the types of androgen deprivation therapy out there. We have both LHRH antagonist and LHRH agonist as the mainstay of treatment for when we use androgen deprivation therapy in men with prostate cancer. We know that that's across many different stages of prostate cancer, and in combination with surgery, with radiation, biochemical failure, newly diagnosed and advanced disease, refractory disease. So, it really is the foundation upon which we build to treat this disease.

If you look at what's out there, the controversy seems to be even more significant at this point. That's one of the reasons that we took a deep dive into this. If we just look what's out there, there's a study called the HERO study [NCT03085095], which was published a couple of years ago in New England Journal of Medicine that was evaluating antagonists relugolix vs an agonist leuprolide. That study reported a higher incidence of cardiovascular events in men that were on the agonist than the antagonist. The outcomes of that were evaluated by the FDA and was not in their indication. The PRONOUNCE trial [NCT02663908] was another trial, which recently closed [and] was supposed to show a difference in the rates of cardiovascular events, [or] MACE events, and it was just the opposite. There were more with the antagonists than with the agonists, 5.5% vs 4.1%. However, only half of the 900 patients were enrolled when the study was stopped. There's been other reviews that are out there that are confusing. I've published data on this, a couple of papers on this over the years, showing that there seemed to be an association with antagonists and agonists and maybe fewer events with the antagonist. We thought that might be related to [follicle-stimulating hormone] FSH.

So, what did we do? We used a large database of over 300 million patients and selected out about 45,000 of them who were on androgen deprivation therapy, and we had the follow-up of many years, up to 10 years. What we found out was the opposite. There were more MACE events, with a hazard ratio of 1.62, with the antagonists vs the agonists. Where we are with this, I think that our results do not support the theory that agonists have a higher cardiovascular risk than antagonists. But again, this is a retrospective [study], but a large database, one of the largest ones out there, supporting this conclusion. We can consider it hypothesis generating, and that further studies are indicated. Right now, I don't think we have strong data that says that the agonists had more cardiovascular events than antagonists.

This transcription has been edited for clarity.

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