A pair of clinical trials showed that combination therapy with relugolix reduced heavy bleeding and pain from uterine fibroids without the risk of side effects from low oestrogen levels.
Relugolix is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist, currently approved for men with advanced prostate cancer. Uterine fibroids are common in women, and a quarter of those who are affected by them experience symptoms such as heavy menstrual bleeding and pain.
Injectable long-acting GnRH agonists are effective treatments for uterine fibroids, but cause BMD loss and thus are not generally eligible for long term use.
In the two trials done in North and South America, Africa, and Europe, 71% and 73% of patients, respectively, who received relugolix together with estradiol and norethindrone acetate had significantly lower blood loss, compared with 19% and 15% in the placebo group.
Similar bone mineral density (BMD) measures were seen in the placebo and relugolix combination therapy groups; but MD decreased among patients who received relugolix monotherapy.
“For the first time, we have an oral treatment that can effectively and safely improve the symptoms of uterine fibroids, particularly heavy menstrual bleeding,” Ayman Al-Hendy, MD, PhD, of the University of Chicago Medicine, stated in an interview. and added that relugolix may be a viable, long-term alternative to the current surgical treatments available for fibroids patients.
“The goal of this program from the beginning was to develop an effective and long-term treatment as a viable alternative to hysterectomy,” Dr Al-Hendy said. “Any patient with uterine fibroids would be a good candidate for this non-surgical treatment.”
Lauren Schiff, MD, associate professor of minimally invasive gynecologic surgery at the school of medicine at the University of North Carolina at Chapel Hill, said that relugolix seems to be a good option for non-surgical treatment of fibroids.
Dr Schiff, who was not involved with the study, said that understanding bone mineral density (BMD) is key for using relugolix past six months. “If the bone density safety measure is maintained for long-term use, then this would be really ideal medication,” she told MedPage Today.
The trial’s primary endpoint was less than 80 ml blood loss, and >50% reduction in total blood loss from trial start. The investigators assessed several secondary outcomes, including amenorrhea, volume of menstrual blood loss, distress, pain, anaemia, fibroid volume, and uterine volume.
Around 388 participants were randomised in the first trial, and 382 in the second.
Around three-quarters of patients who received relugolix combination therapy reached the primary endpoint, with the treatment effects appearing similar baseline characteristics.
Amenorrhea over the last 35 days of the trial occurred in 52% and 50% of participants who received relugolix combination therapy in each trial, respectively. Pain was also reduced in the treatment groups.
Patients who received the combination therapy also had improvements in pain, distress from bleeding and pelvic discomfort, anaemia, and experienced reduced uterine volume. However, significant shrinkage in fibroid volume was not observed.
The prevalence of side effects was similar in the relugolix combination therapy group and the placebo cohort, with hot flashes being the most commonly reported side effect in the trial.
Strict assessment criteria for patients meant generalisability was limited. Additionally, study duration was only six months. The researchers plan to release data from a 28-week extension study, as well as a 52-week randomised-withdrawal trial, and these may shed more light on safety and efficacy in the long term.
Source: MedPage Today
Journal information: Al-Hendy A, et al “Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy” N Engl Med 2021; DOI: 10.1056/NEJMoa2008283.