The risk for a major cardiovascular event was reduced by more than half in patients who received Relumina compared to the hormone associated therapy leuprolide.
Treatment with Relumina (relugolix) demonstrated superior outcomes compared to the hormone associated therapy leuprolide in patients with advanced prostate cancer, according to data from the phase 3 HERO trial presented during the 2020 ASCO Virtual Scientific Program.
“To confirm findings (that) we had established in two prior phase two studies, we randomized in a two to one fashion daily oral relugolix versus every three months subcutaneous or intramuscular leuprolide for patients who had advanced prostate cancer, the primary endpoint of the trial being testosterone suppression throughout a 48-week period,” Dr. Neal D. Shore, medical director for the Carolina Urologic Research Center, said in a recent interview with CURE®’s sister publication CancerNetwork™.
Shore and colleagues enrolled 934 patients with advanced prostate cancer to receive 48 weeks of either Relumina (624 patients) 120 milligrams (mg) administered orally once a day following a one-time 360 mg loading dose or an injection of 22.5 mg leuprolide (310 patients) every three months.
The study’s main outcome was testosterone suppression to castrate levels at 48 weeks. Additional outcomes the researchers aimed to assess included major adverse cardiovascular events, time at which therapies were stopped, recovery of testosterone and reductions in prostate-specific antigen (PSA) levels.
Shore noted that more than 90% of the patients enrolled in the phase 3 HERO trial had at least one cardiovascular risk factor. Additionally, it was common for patients to present with diabetes, hypertension, obesity and have a history of tobacco use.
Patients who received Relumina achieved a 96.7% response rate with sustained castration through week 48 compared to 88.8% in the leuprolide arm.
Patients from the Relumina arm (79.4%) were also more likely to have a PSA response at day 15 and confirmed at day 29 compared to those in the leuprolide arm (19.8%).
More than 90% of patients in both groups experienced at least one side effect. Patients in the leuprolide arm (20.5%) were more likely than those in the Relumina arm (18%) to experience a serious or severe side effect. While deaths were infrequent, 2.9% of patients within the leuprolide arm died vs. 1.1% in the Relumina arm.
The most common side effects in either treatment arm included hot flush, or sudden onset of warmth, fatigue, constipation, diarrhea and hypertension. Patients in the Relumina arm (12.2%) were more likely to report diarrhea than those in the leuprolide arm (6.8%), however all instances of diarrhea were not serious or severe and did not lead to treatment discontinuation.
The data demonstrated that the risk for a major cardiovascular event was reduced by 54% in patients who received Relumina compared to leuprolide.
“Historically, and contemporaneously, we only have a parenteral administration of (testosterone) suppression medications. Whether they're given intramuscularly or subcutaneously, or by an implant, the HERO trial now has established that once-daily oral relugolix, a GNRH antagonist — so you don't get surge of testosterone you avoid clinical flare – will offer patients and physicians another significant tool to consider for achieving testosterone suppression not only because it is highly effective in achieving testosterone suppression, but if patients choose to stop the medication, their testosterone recovery is much faster so they get back to the benefits of having normal testosterone,” Shore concluded. “And even more significantly, the mechanism of action of an antagonist over an agonist will afford patients and physicians some comfort in knowing that there is a marked decrease in the risk of having a cardiovascular event.”