Relugolix Approval Expected to Alter Treatment for Advanced Prostate Cancer
A new drug approved by the Food and Drug Administration (FDA) is expected to immediately affect the treatment of some men with prostate cancer. In a large clinical trial, the drug, relugolix (Orgovyx), was shown to be more effective at reducing testosterone levels in men with advanced prostate cancer than another commonly used treatment, leuprolide (Lupron).
Treatments that block the production of the hormone testosterone by the testes have been the cornerstone of advanced prostate cancer treatment for several decades. Known as androgen deprivation therapy (ADT), these treatments are akin to putting a stopper in a car’s gas tank: robbing prostate tumors of the fuel they need to grow and spread.
In the clinical trial, relugolix was also much less likely than leuprolide to cause serious heart issues, said Neal Shore, M.D., of the Carolina Urologic Research Center, who led the clinical trial on which the approval was based, called HERO. That’s important, Dr. Shore said, because leuprolide and other ADT drugs have been linked with an increased risk of cardiac events, including heart attacks and heart failure.
Going After Testosterone
Prostate cancer that is confined to the prostate is typically treated with surgery or radiation therapy. Once it advances beyond the prostate, either to nearby tissues or to other parts of the body (e.g., bones, liver), ADT is typically used.
Although several drugs for ADT are available, in the United States leuprolide is the most commonly used option. Leuprolide acts on the pituitary gland—a tiny organ within the brain that is responsible for producing a hormone that eventually decreases the production of testosterone by the testicles. It is given to patients as an injection into muscle, typically every few months.
Reducing the production of testosterone to very low levels with drugs is often called medical (or chemical) castration, because it achieves the same results as surgical removal of the testes.
Relugolix also acts on the pituitary gland, but in a way that more directly and rapidly blocks testosterone production in the testes. In addition, it is a pill that patients take every day.
Improved Testosterone Suppression, Lower Cardiac Risks
More than 900 men with advanced prostate cancer whose tumors still relied on testosterone (known as hormone- sensitive prostate cancer) were enrolled in the HERO trial, which was funded by Myovant Sciences, the manufacturer of relugolix.
Participants were assigned at random to take relugolix daily for 48 weeks or to receive leuprolide injections every three months for the same length of time.
Approximately 97% of men treated with relugolix reached and maintained very low testosterone levels through 48 weeks, compared with 89% of men who received leuprolide. In addition, men in the relugolix group also did substantially better on several other measures, including being able to return to normal testosterone levels within a few months of stopping therapy.
Side effects were generally similar in both treatment groups, although diarrhea was more common in men treated with relugolix. The biggest difference, though, was the effect on the heart: Twice as many men in the leuprolide group than in the relugolix group (6.2% versus 2.9%) had a “major adverse cardiovascular event,” which included nonfatal heart attack or a stroke.
When the HERO trial investigators looked specifically at men who had a history of heart problems, the difference in the frequency of these cardiac side effects was even more stark: 17.8% in the leuprolide group versus 3.6% in the relugolix group.