ADT as Treatment in Metastatic Prostate Cancer

Transcript:

Dipti Gupta, MD, MPH: Welcome to this OncLive^® News Network presentation. We are broadcasting live from MJH Studios. Today’s discussion will be focused on the cardiovascular complications of androgen deprivation therapy in patients with prostate cancer.

I am your host, Dipti Gupta, a member of the Cardiology Service at Memorial Sloan Kettering Cancer Center in New York. I am joined today by my colleague, Dr. Susan Slovin, attending member of the Genitourinary Oncology Service, also at the same institution.

During the next hour, we will navigate through some of the questions regarding the use of androgen deprivation therapy for prostate cancer. We will walk you through the metabolic and cardiovascular side effects of ADT, review the differences among available agents, and go through the optimal management of patients with cardiovascular disease and risk factors, both before and during their therapy. During the last few minutes of this broadcast, we will answer questions on this topic from our viewing audience. We invite you to submit questions to our panel by using the entry field that you will see located right below this video.

Dr. Slovin will start us off with a review of how we use androgen deprivation therapy, its effect on hormone-sensitive prostate cancer, and the long-term adverse sequalae we see associated with the use of ADT.

Susan Slovin, MD, PhD: Thank you, Dr. Gupta. Most of you probably know by now that prostate cancer, just like breast cancer, is a hormonally-driven disease. Prostate cancer, however, is driven very heavily by testosterone. Androgen deprivation therapy, or blocking the ability of the body to make testosterone to feed the tumor, remains to be a mainstay of treatment, and it certainly has remained a standard of care for patients who present with metastatic disease. It’s also the mainstay of therapy in people who have high-risk disease, as characterized by a PSA that is greater than 20; a Gleason score of 8, 9, or 10; or a very large, bulky prostate. It’s also very important, nowadays, in the development of control of patients who have metastatic disease at diagnosis.

Androgen deprivation therapy, as many of you know, had its incipience in orchiectomy. That meant removing the testes as a way of making sure that castration was permanent, thereby discontinuing the production of testosterone. It’s really been a very different field since the development of gonadotropin-releasing hormones (GnRH) analogues; or, more recently, antagonists. GnRH agonists have been known as leuprolide, goserelin, buserelin, triptorelin, all by a variety of different names depending on the manufacturer formulation. And then, of course, there’s a GnRH antagonist, degarelix.

Antiandrogens are often given with GnRH agonists. They go by different names—flutamide, nilutamide, bicalutamide—and they bind competitively to the androgen receptor in the cells. They inhibit its activation but, alone, do not lower serum testosterone levels. If you use it as single agent monotherapy, you’ll actually find that testosterone levels skyrocket. But, it does not actually affect the growth of the cancer.

ADT is used as first-line treatment for metastatic disease. It is either given alone or in combination with antiandrogens. More recently, based on a variety of very high-profile phase III trials, we have learned that one could use androgen deprivation therapy early on, at the time of diagnosis, if somebody has metastatic disease. Both the CHAARTED and STAMPEDE trials have shown excellent disease control and improvements in radiographic disease progression by introducing hormone therapy either alone or with docetaxel. Similarly, patients who have, again, metastatic disease have also shown a benefit, based on trials, mainly the STAMPEDE and LATITUDE trials, using an androgen receptor signaling inhibitor such as abiraterone.

Overall, we do know that we can improve survival in patients by using androgen deprivation therapy, inducing tumor responses in greater than 90% of patients with advanced disease—albeit, the time to resistance may be very variable.

Transcript Edited for Clarity