Key Takeaways
- Elinzanetant Significantly Reduces Vasomotor Symptoms. Patients receiving elinzanetant experienced a statistically significant reduction in moderate-to-severe vasomotor symptoms at both four and 12 weeks compared to placebo, with over 70% achieving at least a 50% symptom reduction.
- Improved Sleep and Quality of Life with Elinzanetant. Elinzanetant treatment led to meaningful improvements in sleep disturbances and menopause-related quality of life for women on endocrine therapy for HR-positive breast cancer.
- First Nonhormonal NK-1/NK-3 Antagonist Showing Promise. As the first dual neurokinin-1 and -3 receptor antagonist to reach late-stage development, elinzanetant offers a potential long-term, nonhormonal option for managing endocrine therapy–related symptoms in breast cancer survivors.
Results of the Phase III OASIS-4 trial (NCT05587296) show that elinzanetant significantly reduced vasomotor symptoms (VMS) and improved quality of life and sleep for patients receiving endocrine therapy for hormone receptor (HR)–positive breast cancer.
OASIS-4 Trial Demonstrates Significant Reductions in Vasomotor Symptoms with Elinzanetant
The study data, published by The New England Journal of Medicine (NEJM), hold significance for a patient population with limited options to address the disruptive adverse effects (AEs) associated with endocrine therapy and support the potential of elinzanetant as a long-term, nonhormonal solution for these AEs in breast cancer survivors, according to the study investigators.1,2
“Vasomotor symptoms (also known as hot flashes) are common adverse reactions to endocrine therapy,” the study authors wrote in NEJM. “Vasomotor symptoms associated with endocrine therapy can be more severe than those associated with natural menopause, particularly in younger women who often receive concomitant GnRH analogues. Adverse reactions to endocrine therapy negatively affect health-related quality of life and can lead to nonadherence.”1
The findings from the OASIS-4 trial follow results released last year from the pivotal Phase III OASIS 1 (NCT05042362) and OASIS 2 trials (NCT05099159), in which elinzanetant was found to produce a statistically significant decrease in the frequency and severity of severe VMS in postmenopausal individuals compared to placebo.3-5
Elinzanetant Improves Sleep and Quality of Life in Patients on Endocrine Therapy
Elinzanetant is the first dual neurokinin-1 and 3 (NK-1 and 3) receptor antagonist to reach late-stage development for the non-hormonal treatment of moderate to severe VMS linked to menopause. The oral, once daily medication has been found to modulate estrogen-sensitive neurons in the brain that can cause hyperactivation of the thermoregulatory pathway as estrogen levels decrease, which subsequently impacts body heat control mechanisms and leads to VMS.
“In two pivotal phase 3, 26-week trials (OASIS-1 and OASIS-2) involving women with vasomotor symptoms associated with menopause, treatment with elinzanetant led to a significantly lower frequency and severity of moderate-to-severe vasomotor symptoms, a greater decrease in sleep disturbances, and greater improvements in menopause-related quality of life than placebo,” the study authors wrote. “The OASIS-3 trial supported these results over a longer duration of up to 52 weeks. The current trial, OASIS-4, assessed the efficacy and safety of elinzanetant at a dose of 120 mg for the treatment of vasomotor symptoms associated with endocrine therapy among women with or at high risk for HR-positive breast cancer.”1
OASIS-4 Trial Design, Patient Criteria, and Safety Profile
- The 52-week, interventional, double-blind, randomized, placebo-controlled OASIS-4 trial was conducted at 90 sites in Europe, Canada, Israel, and Kazakhstan.
- Enrollment criteria included women aged 18 to 70 years receiving endocrine therapy comprised of tamoxifen or aromatase inhibitors, with or without GnRH analogues, to treat HR-positive breast cancer or for prevention among patients with a high risk of breast cancer and who had at least 35 moderate-to-severe VMS per week linked to endocrine therapy.
- Investigators randomly assigned patients in a 2:1 ratio to receive 120 mg of elinzanetant once daily for 52 weeks (n = 316) or identical-appearing placebo (n = 158) once daily for 12 weeks followed by 120 mg of elinzanetant once daily for 40 weeks.
- Following this period, trial patients were tracked for an additional four weeks.
Consistent Findings Across OASIS Trials Support Elinzanetant's Efficacy
- Mean daily frequency at baseline of moderate-to-severe VMS was 11.4 episodes (95% confidence interval [CI], 10.7 to 12.2) in the elinzanetant cohort compared to 11.5 episodes (95% CI, 10.5 to 12.5) in the placebo–elinzanetant cohort.
- Mean change from baseline after four weeks in the mean daily frequency of moderate-to-severe VMS was −6.5 episodes (95% CI, −7.2 to −5.8) in the elinzanetant cohort compared to −3.0 episodes (95% CI, −3.9 to −2.2) in the placebo cohort (least-squares mean difference, −3.5 episodes; 95% CI, −4.4 to −2.6; P<0.001).
- Mean change after 12 weeks was −7.8 episodes (95% CI, −8.5 to −7.1) in the elinzanetant cohort compared to −4.2 episodes (95% CI, −5.2 to −3.2) in the placebo cohort (least-squares mean difference, −3.4 episodes; 95% CI, −4.2 to −2.5; P<0.001).
- Across the first 12 weeks, 69.8% of patients in the elinzanetant cohort reported at least one AE compared to 62.0% in the placebo cohort.
- The most common AEs were headache, fatigue, and somnolence.
- Serious AEs during the first 12 weeks were reported in eight patients in the elinzanetant cohort compared to one patient in the placebo cohort.
“Although there is currently no defined threshold for a clinically meaningful reduction in the frequency of moderate-to-severe vasomotor symptoms among women with vasomotor symptoms associated with endocrine therapy, a reduction from baseline of at least 50% is considered to be clinically meaningful on an individual level in the natural-menopause population,” the study authors concluded. “In exploratory analyses, more than 70% of the participants treated with elinzanetant had a reduction in symptoms of at least 50% at 12 weeks, which is consistent with the results of the OASIS-1 and OASIS-2 trials.”1
References
1. Cardoso F., et al. Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer. N Engl J Med 2025. DOI: 10.1056/NEJMoa2415566.
2. A Study to Learn More About How Well Elinzanetant Works and How Safe it is Compared to Placebo for the Treatment of Hot Flashes Caused by Anti-cancer Therapy in Women With, or at High Risk for Developing Hormone-receptor Positive Breast Cancer (OASIS-4). ClinicalTrials.gov. Updated April 15, 2025. Accessed June 18, 2025. https://clinicaltrials.gov/study/NCT05587296
3. Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA. Published online August 22, 2024. doi:10.1001/jama.2024.14618
4. A Study to Learn More About How Well Elinzanetant Works and How Safe it is for the Treatment of Vasomotor Symptoms (Hot Flashes) That Are Caused by Hormonal Changes Over 26 Weeks in Women Who Have Been Through the Menopause (OASIS-1). ClinicalTrials.gov. June 27, 2024. Accessed June 18, 2025. https://clinicaltrials.gov/study/NCT05042362.
5. A Study to Learn More About How Well Elinzanetant Works and How Safe it is for the Treatment of Vasomotor Symptoms (Hot Flashes) That Are Caused by Hormonal Changes Over 26 Weeks in Women Who Have Been Through the Menopause (OASIS-2). ClinicalTrials.gov. May 29, 2024. Accessed June 18, 2025. https://clinicaltrials.gov/study/NCT05099159
