Men diagnosed with advanced prostate cancer have a new arsenal on their side in fighting this disease. Relugolix, an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, was approved by the FDA in late 2020 and is shown to be more effective at reducing testosterone levels in men with advanced disease than the commonly used treatment called Lupron. Lupron is an injectable medication that belongs to a class of drugs called luteinizing hormone-releasing hormone (LHRH) agonists. These medications block the production of LHRH in the body, causing the testicles to produce less testosterone. Lupron is one of several drugs that doctors may prescribe to fight prostate cancer by reducing testosterone levels in the body.
History of ADT for advanced prostate cancer
For decades, advanced prostate cancer treatment has focused on blocking the production of testosterone with the use of androgen deprivation therapy (ADT). ADT is meant to block testosterone since this hormone promotes prostate cancer tumors to grow and spread, which it has been shown to do. But evidence has found that ADT increases cardiovascular risk, particularly in men with preexisting cardiovascular disease. This increased risk may also apply to men using short-term ADT.
Study finds Relugolix more effective for men with cardiac issues
Lupron is one of the medications for ADT that for some men has had side effects of causing serious heart issues. Lupron, along with other ADT drugs, has been linked to an increased risk of including heart attacks and heart failure. Now, a large clinical trial has found that Relugolix is much less likely than Lupron to cause heart issues. This is good news for any man diagnosed with advanced prostate cancer and could be at an increased risk of cardiac complications when being treated for his disease.
For the trial, 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 Lupron injections every 3 months, also for 48 weeks.
For the participants assigned to taking Relugolix, an overwhelming majority of 97% reached and maintained very low testosterone levels during the 48 weeks compared with 89% of men who received Lupron. The men taking Relugolix also did much better on being able to return to normal testosterone levels within a few months after stopping therapy. This was a significant finding as suppressing testosterone for long periods can lead to side effects such as fatigue, hot flashes, and bone issues.
When the HERO trial reviewed how men using Relugolix with a history of heart problems performed compared to the frequency of cardiac side effects of the men using Lupron, the men using Lupron experienced 17.8% cardiac side effects compared to only 3.6% of the men using Relugolix.
FDA approval of Relugolix welcomed news
The approval by the FDA for Relugolix is exciting and encouraging for men with advanced prostate cancer along with heart issues. This likely will become a new standard of care for men with advanced prostate cancer. Relugolix is an oral medication taken daily whereas Lupron is an injectable typically taken every few months. Relugolix works by binding to receptors for the hormone GnRH on the pituitary gland, decreasing the production of other hormones by the pituitary and, consequently, testosterone by the testes.
Before prostate cancer has reached an advanced stage, the disease 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.
Relugolix is not the first GnRH antagonist to be approved by the FDA to treat men with advanced prostate cancer. More than a decade ago, Firmagon was FDA approved but this medication, given as a monthly injection, can cause intense pain at the injection site, limiting its use.
The only drawback researchers viewed as a possible negative was the fact that Relugolix is to be taken daily as an oral medication as opposed to having an injection given every few months. Some men may forget to take the medication or have difficulty taking a pill every day.