O-191 Effects of relugolix combination therapy (Relugolix-CT) on uterine fibroid (UF) and uterine volume through 52 weeks: post hoc analysis of the LIBERTY Long-Term Extension study

Abstract

Abstract Study question How does baseline UF and uterine volume impact the proportion of women achieving meaningful UF and uterine volume reductions with Relugolix-CT through 52 weeks? Summary answer Women with larger UF and uterine volumes at baseline may be more likely to experience clinically meaningful reductions of UF and uterine volume with Relugolix-CT. What is known already In the randomised, Phase 3 LIBERTY 1 and 2 pivotal studies, the efficacy and safety of once-daily Relugolix-CT (relugolix 40 mg, estradiol 1 mg, norethisterone acetate 0.5 mg) were demonstrated in premenopausal women (aged 18–50 years), with a significant reduction in UF-associated heavy menstrual bleeding (HMB) vs placebo, and preserved bone mineral density (BMD) through 24 weeks. The open-label, 28-week LIBERTY Long-Term Extension (LTE) study continued to demonstrate sustained menstrual blood loss reductions and preservation of BMD, alongside reductions in UF and uterine volume. Study design, size, duration The LIBERTY 1 and 2 studies of Relugolix-CT were conducted in 770 premenopausal women with UF-associated HMB. Women were randomised 1:1:1 to receive Relugolix-CT or placebo for 24 weeks, or delayed Relugolix-CT (relugolix 40 mg alone for 12 weeks, then Relugolix-CT for 12 weeks). Women who completed the pivotal trials were eligible to participate in the LIBERTY LTE study, receiving open-label Relugolix-CT for an additional 28 weeks. Participants/materials, setting, methods Endpoints of the LTE included change from baseline to Week 52 in UF and uterine volume. This post hoc analysis assessed the proportion of women who experienced a clinically meaningful reduction in UF or uterine volume of > 25% or > 50% through 52 weeks of Relugolix-CT. Subgroup analyses were performed to descriptively summarise the impact of UF and uterine volume at baseline (<25cm3 or ≥ 25cm3; <300cm3 or ≥ 300cm3, respectively) on change in UF and uterine volume. Main results and the role of chance In total, 477 women enrolled in the LTE, 363 completed 52 weeks of treatment, and 163 received Relugolix-CT continuously up to 52 weeks. At baseline, the mean (standard deviation) volume of the largest UF was 80.0 (145.1) cm3; mean (SD) uterine volume was 386.7 (320.5) cm3 in the Relugolix-CT group. At Week 24, 52.6% and 30.3% of women in the Relugolix-CT group experienced >25% and >50% reduction in UF volume, respectively. These proportions increased to 61.1% and 36.6%, respectively, at Week 52. For uterine volume, 36.1% and 4.5% experienced a > 25% and >50% reduction at Week 24, increasing to 41.2% and 9.6% at Week 52. At Week 52, of 81 women with a baseline UF volume of < 25cm3, 52.4% and 27.0% experienced a > 25% and >50% reduction in UF volume, respectively; 69.1% and 45.6% of 81 women with a baseline UF volume of ≥ 25cm3 experienced >25% and >50% reductions in UF volume, respectively. At Week 52, of 96 women with a baseline uterine volume of < 300cm3, 38.5% and 6.4% experienced a > 25% and >50% reduction in uterine volume; 44.8% and 13.8% of 67 women with a baseline uterine volume of ≥ 300cm3 experienced >25% and >50% reductions in uterine volume. Limitations, reasons for caution The study was conducted as an open-label study without a control group over the 28 weeks of the extension period. The present data are from a post hoc analysis of LIBERTY data without predefined criteria. Wider implications of the findings Treatment with Relugolix-CT led to a substantial reduction of UF and uterine volume in a large proportion of women with UF-associated HMB. Women with larger UF and uterine volume at baseline may be more likely to experience substantial reductions of UF and uterine volume. Trial registration number NCT03049735, NCT03103087, NCT03412890