Be a HERO.

Top Line: We’re all keenly aware of the potential adverse cardiac effects of androgen deprivation therapy and their competing cause of mortality in some men with prostate cancer.

The Study: It has been observed that cardiovascular effects may be less when using a GnRH antagonist, such as relugolix, instead of a LHRH/GnRH agonist, such as the better-known leuprolide. In the HERO trial, over 900 men with advanced prostate cancer (~50% with biochemical recurrence) were randomized to receive either leuprolide every 3 months or oral relugolix 120 mg daily, both for a total of 48 weeks. The trial had a number of very interesting outcomes. First, relugolix provided superior rates of castration-level testosterone (97% versus 89%). Second, 56% of men had castrate-level testosterone only 4 days after starting relugolix compared to 0% on leuprolide. Third, testosterone recovery was significantly greater 90 days after stopping the drug with a testosterone level nearly 5 times higher. Last, the rate of major adverse cardiac events was 3% with relugolix compared to 6% with leuprolide. In men with a history of prior major cardiac events, that difference was even bigger at 4% with relugolix versus 18% with leuprolide. Side effects were pretty similar, with only a slight increase in mild diarrhea with relugolix. While this trial was performed in men with advanced prostate cancer, these results could have important implications on the choice of short-term ADT in men receiving radiation.

TBL: The oral GnRH antagonist relugolix provides superior androgen suppression compared to the long-reigning leuprolide with half the rate of major adverse cardiac events. | Shore, N Engl J Med 2020