Pei-Chun McGregor, MD, cardio-oncologist and director of Ambulatory Cardiology at VA Boston Healthcare System, instructor in medicine, Brigham and Women’s Hospital, discusses the goals of androgen deprivation therapy (ADT) in the treatment of patients with prostate cancer.

ADT is meant to suppress testosterone levels, which is the cause of cancer proliferation in prostate cancer. Those levels can be suppressed either through gonadotropin-releasing hormone antagonists and agonists or through newer agents, such as the CYP17 inhibitors or the antiandrogens, explains McGregor.

By suppressing testosterone levels, ADT is essentially chemically-induced menopause, adds McGregor. Therefore, patients will experience all the events associated with menopause, which include loss of libido, erectile dysfunction in men, hot flashes, muscle wasting, development of subcutaneous fat, anemia, fatigue, and cognitive impairment.

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Dr. McGregor on the Goals of ADT in Prostate Cancer

Pei-Chun McGregor, MD, cardio-oncologist and director of Ambulatory Cardiology at VA Boston Healthcare System, instructor in medicine, Brigham and Women’s Hospital, discusses the goal of the phase IIb PRONOUNCE trial in prostate cancer.

This trial is still ongoing, but it is expected to complete within the next year or 2, says McGregor. It's a multicenter, randomized control trial looking specifically at cardiovascular events in patients with prostate cancer and any underlying pre-existing cardiovascular disease.

Investigators are planning to randomize patients to receive a GnRH antagonist, degarelix (Firmagon), versus leuprolide, which is an agonist. The expected enrollment is 900 patients. The primary endpoint is time from randomization to the first major adverse cardiovascular event (MACE). The secondary endpoints will be comprised of individual MACE endpoints, says McGregor. Investigators are also planning to look at biomarkers—specifically, cardiovascular, inflammatory, and immune biomarkers. This will be the first trial to prospectively study this. Hopefully, the trial will answer the question of whether GnRH agonists have a potentially adverse signal toward the cardiovascular system over the antagonists, concludes McGregor.

Pei-Chun McGregor, MD, cardio-oncologist and director of Ambulatory Cardiology at VA Boston Healthcare System, instructor in medicine, Brigham and Women’s Hospital, discusses the hope for the phase IIb PRONOUNCE trial in prostate cancer.

Dr. McGregor on the Goal of the PRONOUNCE Trial in Prostate Cancer

Pei-Chun McGregor, MD, cardio-oncologist and director of Ambulatory Cardiology at VA Boston Healthcare System, instructor in medicine, Brigham and Women’s Hospital, discusses guidelines regarding androgen deprivation therapy (ADT)-associated cardiac adverse events (AEs) in prostate cancer.

There are some guidelines for community doctors that offer insight on how to navigate care for patients who may be at risk of developing ADT-associated cardiac AEs. This will help bring awareness to communities that are not as well versed on the association of ADT with cardiovascular disease, says McGregor. Notably, most internists do not know that ADT can cause adverse changes metabolically. As such, they might not be checking lipids or blood pressure.

Even some cardiologists may not know what to watch for. Some of the medications that are used to block testosterone have also been shown to increase a patient’s QT. If a patient’s QT is increased, then they’re at risk for arrhythmias, which means they can potentially die from an abnormal heart rhythm. It’s about bringing awareness to the community, concludes McGregor, an effort that guidelines are currently spearheading.

Dr. McGregor on Guidelines Regarding ADT-Associated Cardiac AEs in Prostate Cancer

Pei-Chun McGregor, MD, cardio-oncologist and director of Ambulatory Cardiology at VA Boston Healthcare System, instructor in medicine, Brigham and Women’s Hospital, discusses the data behind the potential link between cardiac complications and androgen deprivation therapy (ADT) in prostate cancer.

The trials that have been conducted to date show conflicting data, says McGregor. The bulk of data come from observational and retrospective studies suggesting that there could be a potential link between cardiac complications and ADT. For example, the VA trial looked at more than 37,000 patients and showed that the GnRH agonist cohort experienced significant effects on the cardiovascular system. Specifically, that cohort had increasing risks for heart disease, the rates of heart attacks, strokes, and sudden cardiac death, adds McGregor.

However, a lot of these data come from post-hoc analyses. Currently, there is no randomized control trial that is looking specifically at cardiovascular disease as an endpoint. Most of the negative trials showing no clear link between heart disease and ADT are from Europe, says McGregor. Even so, the FDA and the European Medicines Agency have advocated for a label change due to the potential link. Additionally, the 2010 American Heart Association guideline along with the American Cancer Society guideline clearly states that although the data may be confusing, there is likely a link between ADT and cardiac complications.

Pei-Chun McGregor, MD

Articles

Dr. McGregor on the Goals of ADT in Prostate Cancer

Dr. McGregor on the Goal of the PRONOUNCE Trial in Prostate Cancer

Dr. McGregor on Guidelines Regarding ADT-Associated Cardiac AEs in Prostate Cancer

Dr. McGregor on Data Evaluating the Link Between Cardiac Complications and ADT in Prostate Cancer