Relugolix Shows Better Castration Control in HERO Study of Advanced Prostate Cancer

By Gene Emery

June 01, 2020

(Reuters Health) - The experimental drug relugolix provides better castration control with fewer cardiovascular events than conventional advanced prostate cancer therapy with leuprolide, doctors behind the international phase 3 HERO study reported Friday.

"This is a remarkably important advancement for advanced prostate cancer," chief author Dr. Neal Shore, medical director of the Carolina Urologic Research Center in Myrtle Beach, South Carolina, told Reuters Health in a telephone interview.

The results were detailed online during the American Society of Clinical Oncology's 2020 Virtual Scientific Program and published by The New England Journal of Medicine. Myovant Sciences, which is developing relugolix, paid for the study.

HERO compared the two treatments among 930 men, finding that castration was maintained from day 29 through 48 weeks in 96.7% of those receiving relugolix versus 88.8% of those taking leuprolide (P<0.001 for relugolix's superiority)

In addition, once daily relugolix lowered the odds of a major adverse cardiovascular event (MACE) by 54% compared to leuprolide, which was administered by injection every 3 months. Specifically, the rates were 2.9% with relugolix versus 6.2% with leuprolide.

Among men with a history of cardiovascular events, the MACE rates were 3.6% versus 17.8%, respectively.

"Cardiovascular complications are very common in this elderly male population. Many men being treated for prostate cancer end up succumbing to cardiovascular mortality," which is why the U.S. Food and Drug Administration put a black box warning on all luteinizing hormone-releasing hormone agonist medications, said Dr. Shore.

Doctors have been looking for a better alternative to existing castration therapies because the agonists given to lower testosterone "cause the exact opposite of what we're trying to do for several weeks," he said.

Instead, relugolix acted rapidly, with 56.0% of patients seeing castration on day 4 versus none of the patients who receive leuprolide.

And while 79.4% taking the once-daily oral drug had a PSA response on day 15, the rate was just 1.0% with leuprolide, where 30% of recipients typically experience a pain reaction from their injections.

When the researchers looked at testosterone recovery after the treatments were halted for 90 days, a normal hormone level was achieved in 54% of the relugolix group versus 3% among those taking leuprolide (P=0.002).

"That's a very nice thing if you're trying to get back your energy level and your sex drive," Dr. Shore said.

Hot flashes occurred in a little over half the patients in each group. Mild to moderate diarrhea was also seen in both groups, but it was more common with relugolix, where the incidence was 12.2% compared with 6.8% among the control patients.

SOURCE: The New England Journal of Medicine, online May 29, 2020