Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Oral relugolix vs leuprolide in advanced prostate cancer

Key clinical point: In men with advanced prostate cancer, relugolix achieves rapid, sustained suppression of testosterone levels superior to that of leuprolide, with a reduced risk of major adverse cardiovascular events (MACE).

Major finding: Patients treated with relugolix had a significantly higher rate of maintained castrate levels of testosterone vs. those treated with leuprolide (96.7% vs. 88.8%; difference, 7.9% points; P less than .001 for superiority). The risk of MACE was lower with relugolix (hazard ratio, 0.46; 95% confidence interval, 0.24-0.88). Grade 3-4 adverse event rates were 18.0% with relugolix and 20.5% with leuprolide.

Study details: In this phase 3 HERO trial, 934 patients with advanced prostate cancer were randomly assigned 2:1 to receive either oral relugolix or leuprolide depot injections for 48 weeks.

Disclosures: This study was funded by Myovant Sciences.


"Androgen deprivation is the backbone of treatment for patients with high risk, earlier stage prostate cancer and those with advanced disease. Currently, LHRH agonists are widely utilized to achieve androgen deprivation but are associated with initial testosterone flares and cardiovascular side effects. In addition, FSH is not fully suppressed by these agents. In the HERO trial, Shore et al. evaluated whether the orally available GnRH antagonist, relugolix, can achieve similar testosterone depletion and clinical results to the LHRH agonist leuprolide. Compared with leuprolide, relugolix was associated with somewhat improved testosterone suppression and fewer major cardiovascular events compared with leuprolide. Further studies will be needed to determine whether such effects are associated with improved prostate cancer-specific outcomes. However, based on the results of the HERO trial, relugolix appears to be an option that could be considered for some patients.”

Mark Klein, MD


Shore ND et al. N Engl J Med. 2020 Jun 4. doi: 10.1056/NEJMoa2004325.