For men with advanced prostate cancer, a new hormone therapy pill works better than standard injections — and carries a much lower risk of heart attack or stroke, a clinical trial has found.
The drug, called relugolix, is not yet approved by the U.S. Food and Drug Administration. If it gets the green light, however, it would be "game-changing," said Dr. Neal Shore, lead researcher on the trial.
Hormone therapy has long been a standard treatment for advanced prostate cancer — including cases where the tumor has spread beyond the prostate gland or recurred after treatment with surgery or radiation.
The goal is to suppress androgen hormones, including testosterone, because they fuel the growth of prostate tumors.
Right now, that's usually done with injection drugs called LHRH agonists. The problem is that the drugs initially cause a surge in testosterone, before drastically cutting levels of the hormone. That surge can cause cancer-related symptoms, such as bone pain and urinary problems, to flare.
"It's like having a race and telling people to first take 10 steps back, and then start running," said Shore, medical director of the Carolina Urologic Research Center in Myrtle Beach, South Carolina.
In contrast, relugolix — taken as a daily pill — rapidly lowers testosterone levels, the trial found.
Even more importantly, Shore said, it had a lower risk of cardiovascular "events" — defined as a heart attack, stroke or death from any cause.
Over 48 weeks, that risk was 54% lower among men given relugolix, versus a standard LHRH agonist called leuprolide.
"That is very significant," said Dr. William Cance, chief medical and scientific officer for the American Cancer Society.
"This drug pretty much checks all the boxes," said Cance, who was not involved in the study.
More research is needed on the medication's long-term performance, he noted. But if it's approved, Cance said, it would likely be favored over LHRH agonists.
The findings are being published in the New England Journal of Medicine (NEJM), and simultaneously reported Friday at the virtual annual meeting of the American Society of Clinical Oncology.
The trial, funded by drug maker Myovant Sciences, involved 930 men with advanced prostate cancer. They were randomly assigned to either take relugolix or receive leuprolide injections every three months.
Within days, men on relugolix saw their testosterone levels drop to low levels. Those given leuprolide showed the expected testosterone rise before dropping to the desired level around day 29.
And once the drug was stopped, testosterone levels returned to normal much more readily in men taking relugolix.
"So you can more easily turn it up and turn it down," Cance said. That's important, he noted, for men who go on shorter courses of hormone therapy — related to radiation treatment, for example.
The most critical difference, though, was in safety. Just over 6% of men on leuprolide suffered a heart attack or stroke, or died — compared with just under 3% of those on relugolix, the findings showed.
Shore said many men with prostate cancer ultimately die of cardiovascular disease. With improved treatments preventing deaths from the cancer itself, around 27% to 34% of patients die from heart-related causes, studies show.
It's not clear why LHRH agonists have higher cardiovascular risks, Cance said.
But researchers have speculated that the drugs may cause pre-existing plaques in the arteries to rupture. That can block the blood vessel and trigger a heart attack or stroke.
Relugolix does carry the usual side effects of testosterone suppression, however. Hot flashes, fatigue, constipation and diarrhea were most common.
Meanwhile, an oral hormone medication already on the market seems to help certain prostate cancer patients live longer. That's according to a separate study also published in the NEJM and presented at the meeting.
The trial included 1,400 men whose prostate cancer was progressing despite standard hormonal therapy, but had not yet spread to distant sites in the body. They were randomly assigned to add either the drug — called enzalutamide (Xtandi) — or a placebo pill to their hormonal therapy.
Overall, men on enzalutamide survived longer. Their median survival was 67 months, meaning half lived longer, and half died sooner. Median survival in the placebo group was 56 months.
The drug is already approved for these patients, based on data showing it cut their risk of dying from prostate cancer. The new findings show that their overall survival is better, too.