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Expert Discusses Degarelix and Other Developments in Prostate Cancer

Chelsea LoCascio
Published: Tuesday, Nov 14, 2017

Guru Sonpavde, MD
Guru Sonpavde, MD
The question of when to administer the LHRH receptor antagonist degarelix (Firmagon) to patients with castration-sensitive prostate cancer versus an agonist still remains to be answered, according to Guru P. Sonpavde, MD.

“Unfortunately, it looks like we may never have—at least with the trials ongoing and that have been done—a definitive answer to the question of whether we should be using degarelix for all patients,” said Sonpavde. “At the moment, all we can say is high-volume disease and in patients with a history of cardiovascular events, it might make sense to use degarelix based on the data we have.”

In an interview during the 2017 OncLive® State of the Science SummitTM on Genitourinary Cancers, Sonpavde, director of Bladder Cancer at the Dana-Farber Cancer Institute, discussed degarelix, androgen-deprivation therapy (ADT), and ongoing trials with immunotherapy that are crucial to advancing the treatment of patients with prostate cancer.

OncLive: What did you focus on in your presentation on prostate cancer?

Sonpavde: In the talk, I focused on degarelix, which is an LHRH receptor antagonist as opposed to the LHRH agonists that are in use for a longer time. Essentially, the data right now for degarelix are that this drug suppresses testosterone more rapidly and might have some benefit in patients with a history of cardiovascular events. It seems like patients who have had cardiovascular events might have fewer cardiovascular events on degarelix as opposed to LHRH agonists. There might also be a benefit in terms of prostate-specific antigen progression-free survival, but we’re not quite sure about the efficacy yet because these trials were not designed to look at efficacy as the primary endpoint.

At this time, it will be reasonable to use degarelix in patients with cardiovascular events based on the lower cardiovascular event rate with degarelix compared with LHRH agonists and in patients with high-volume disease, especially spine metastasis where you want to have rapid control of the disease to prevent cord compression. However, we don’t have a phase III trial looking at efficacy. There is a trial going on that is looking at…[an] LHRH agonist verus degarelix, with cardiovascular events as the primary endpoint. That will answer that question more definitively regarding cardiovascular events.

What questions do we still have with agonists and antagonists?

What is not clear is, should we be giving the antagonists to all patients with castration-sensitive disease? This is not clear. The phase III trial that’s been done so far focused on testosterone suppression as the primary endpoint and not antitumor efficacy. The trial going on now—the PRONOUNCE trial—is looking at cardiovascular events as the primary endpoint.

How can community oncologists manage comorbidities that these patients might have? Is there any chance that you might need to switch therapies because of them?

ADT does lead to some adverse events—impotence, bone loss, bone thinning, dyslipidemia, glucose intolerance, and a slight increase in cardiovascular events. We are not sure about cardiovascular mortality, but there is an increase in cardiovascular events. Therefore, you have to pay attention to weight, lipid control, blood pressure control, and perhaps aspirin prophylaxis in patients at high risk for cardiovascular events. A lot of these common-sense things should be paid attention to, as well as modify the cardiovascular profile before you even start ADT. For example, you might want to get control of the blood pressure and lipids, or at least start controlling these comorbidities, when you’re about to start ADT.

You also spoke about the STAMPEDE and LATITUDE trials. What questions do we still have following the results of these studies?

Both the STAMPEDE and LATITUDE trials looked at the value of adding abiraterone acetate (Zytiga) plus prednisone to patients with castration-sensitive disease. LATITUDE was focused on patients with high-risk metastatic castration-sensitive disease; whereas, STAMPEDE was a more heterogeneous patient population of both metastatic and nonmetastatic patients. Both trials looked very similar. The addition of abiraterone plus prednisone to ADT improves survival with a hazard ratio that was very similar, around 0.63, for both trials.

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