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ADT Options for Prostate Cancer Come Out Even for Heart Safety

— But low enrollment brought PRONOUNCE trial to an early close

MedpageToday

Androgen deprivation therapy (ADT) options for prostate cancer seemed to have a similar impact on the risk of cardiovascular events among people with documented heart disease, according to results from the PRONOUNCE trial, although the study was terminated early due to slow accrual.

In 545 men, there was no statistically significant difference in the rate of a major adverse cardiovascular event (MACE) at 12 months between patients treated with degarelix (Firmagon) and those treated with leuprolide, reported Renato Lopes, MD, of Duke University Medical Center in Durham, North Carolina, at the European Society of Cardiology (ESC) virtual meeting.

The degarelix group saw a 5.5% MACE rate versus 4.1% in the leuprolide groups (P=0.53). This primary endpoint was defined as a composite of death, myocardial infarction, or stroke through 12 months.

PRONOUNCE was set to recruit 900 men, but because of sluggish enrollment, settled at 545 (average age 73). Previous research had indicated that gonadotropin-releasing hormone (GnRH) antagonists such as degarelix may be associated with a preferable cardiovascular safety profile, Lopes explained. PRONOUNCE was the first randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist with a GnRH agonist (leuprolide) in patients with prostate cancer.

About 50% of all patients with prostate cancer will be prescribed ADT, such as orchiectomy, testosterone antagonists, or modulation of the GnRH, at some point in their illness, and ADT has been associated with heart disease and stroke, particularly in men with pre-existing cardiovascular disease (CVD), he stated. More than 1 million men globally are diagnosed with prostate cancer every year, and these patients are at , as well as more likely to die from the latter than their healthy peers.

"There is an ongoing need to understand the cardiovascular effects of oncological treatments as cancer survivorship increases and competing non-cancer death becomes more likely," Lopes said in a press release. "PRONOUNCE provides a model for the interdisciplinary collaboration between oncologists and cardiologists with a shared goal of evaluating the impact of cancer therapies on cardiovascular outcomes."

ESC spokesperson Sarah Clarke, MD, of Royal Papworth Hospital in Cambridge, England, agreed, telling ľֱ, "This is a really good example of how medical teams have to work together -- cardiologists, oncologists, urologists," she said. "We have to work more as a team now across the board, more than we used to do. The selection of treatments requires engagement from the wider community. This trial illustrates the need for that discussion."

As for choosing between a GnRH antagonist and a GnRH agonist in the context of cardiovascular health, "There are two perspectives on this," commented ESC press conference moderator Carlos Aguiar, MD, of Hospital Santa Cruz in Lisbon, Portugal. "One is from the cancer side and the other is the cardiovascular disease side. The oncology part of the side should be left to the oncologists. This was more a cardiovascular story."

"These agents are employed because of their abilities to attack the cancer by depriving them of the hormones needed for growth," he added. "But in doing this, you want to be sure that there is no higher risk for cardiovascular disease, so you want to make sure these drugs are cardiovascular safe. In this case, the two treatments were similar so I think both are equally safe as major cardiovascular event points go."

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    Ed Susman is a freelance medical writer based in Fort Pierce, Florida, USA.

Disclosures

The study was funded by Ferring Pharmaceuticals.

Lopes and Clarke disclosed no relationships with industry.

Aguiar disclosed relationships with Bayer, Bristol Myers Squibb, Daiichi Sankyo, and Pfizer.

Primary Source

European Society of Cardiology

Lopes R, et al "PRONOUNCE: comparing cardiovascular safety of degarelix vs. leuprolide in patients with advanced prostate cancer and cardiovascular disease" ESC 2021.