Impact of elinzanetant on sleep disturbances and quality of life in women undergoing adjuvant endocrine therapy for breast cancer: Phase 3 OASIS 4 trial.

12063 Background: Vasomotor symptoms (VMS) and sleep disturbances are common in women taking adjuvant endocrine therapy (AET) for hormone receptor-positive (HR+) breast cancer and can impact quality of life and treatment adherence, potentially affecting breast cancer outcomes. There are few efficacious treatments and none approved in this indication. Elinzanetant (EZN) is a dual neurokinin-1 and -3 receptor antagonist in development for the treatment of VMS. Methods: OASIS 4 (NCT05587296) is a 52-week randomized, placebo-controlled phase 3 trial evaluating the safety and efficacy of EZN for the treatment of VMS in women taking AET for HR+ breast cancer. Women aged 18–70 years being treated for, or at high risk of developing, HR+ breast cancer and experiencing ≥35 moderate-to-severe VMS/week associated with tamoxifen/aromatase inhibitors were randomized 2:1 to receive EZN 120 mg for 52 weeks or placebo for 12 weeks followed by EZN for 40 weeks. Impact of EZN on sleep disturbances and menopause-related quality of life were evaluated as key secondary endpoints, measured by mean changes from baseline to week 12 in Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form (PROMIS SD SF) 8b total T-score and Menopause-specific Quality-Of-Life questionnaire (MENQOL) total score, respectively. These endpoints were analyzed using a mixed model with repeated measures (one-sided p-values). Results: At baseline, mean (standard deviation [SD]) PROMIS SD SF 8b total T-scores were 60.6 (6.3) in the EZN group and 60.7 (6.8) in the placebo group, corresponding to moderate sleep disturbances based on established thresholds in a reference population. At week 12, reductions from baseline in PROMIS SD SF 8b total T-score were -10.6 (8.2) and -4.1 (7.4) in respective groups, suggesting an improvement in sleep disturbance. Reductions between EZN and placebo showed a statistically significant difference (least squares [LS] mean difference [95% confidence interval (CI)]: -6.1 [-7.5, -4.8]; p<0.0001). Mean (SD) MENQOL total scores at baseline were 4.8 (1.2) in the EZN group and 4.8 (1.3) in the placebo group. At week 12, reductions from baseline in MENQOL total score were -1.3 (1.1) and -0.5 (1.2), respectively, corresponding to an improvement in menopause-related quality of life. Reductions between EZN and placebo showed a statistically significant difference (LS mean difference [95% CI]: -0.7 [-0.9, -0.5]; p<0.0001). Reductions in PROMIS SD SF 8b total T-scores and MENQOL total scores were maintained in both treatment groups throughout the 52-week treatment period. Conclusions: EZN demonstrated efficacy in reducing sleep disturbance and improving quality of life in women undergoing AET for breast cancer. Concomitant intake of EZN and AET may improve tolerability and adherence to AET, with a potentially favorable impact on breast cancer outcomes. Clinical trial information: NCT05587296 .