Relugolix Combination Therapy Improves Uterine Fibroid Symptoms Independent of Fibroid Location [A77

Abstract

INTRODUCTION: In the Phase 3, replicate, institutional review board-approved LIBERTY 1 and 2 studies, relugolix combination therapy (Relugolix CT; once daily relugolix 40 mg, estradiol 1 mg, norethindrone acetate 0.5 mg) improved uterine fibroid (UF)-associated heavy menstrual bleeding (HMB), pain, and quality of life (QoL). We report the impact of location (submucosal, intramural, or subserosal) of the largest fibroid on treatment outcomes through 24 weeks. METHODS: Premenopausal women were randomized to relugolix combination therapy or placebo for 24 weeks. Location of the largest fibroid was investigator-defined using ultrasound; FIGO type 0/1 fibroids were excluded. Menstrual blood loss (MBL) volume was measured by alkaline hematin method (responders: MBL volume < 80mL and ≥50% reduction from baseline over last 35 days of treatment). Pain and other UF-associated symptoms were evaluated using the Numerical Rating Scale and UF-QoL Questionnaire (Symptom Severity) in this post-hoc analysis. RESULTS: In the relugolix combination therapy (N=253) and placebo (N=256) groups, the largest fibroid was categorized by location as subserous (N=50 and N=58), intramural (N=115 and N=130), submucosal (N=46 and N=43) or “other/unknown” (N=119 and N=106). Baseline characteristics, including MBL volume, pain and QoL scores, were similar between subgroups. In all fibroid subgroups, women randomized to relugolix combination therapy had comparable responder rates of 76.0%, 79.1%, 80.4%, and 65.6% at week 24 that were higher than with placebo: 24.1%, 16.2%, 14.0%, and 16.0% (all nominal P<.0001). Across all subgroups, women randomized to relugolix combination therapy experienced significant reductions in MBL volume, UF-associated pain and symptom severity versus placebo. CONCLUSION: Relugolix combination therapy improves HMB and other UF-associated symptoms independent of the location of the largest fibroid.