By Lynda Williams, medwireNews Reporter
medwireNews: The neurokinin-targeted agent elinzanetant significantly improves vasomotor symptoms in women undergoing endocrine therapy for hormone receptor-positive breast cancer, research indicates.
The OASIS-4 study was published in The New England Journal of Medicine to coincide with its presentation at the 2025 ASCO Annual Meeting in Chicago, Illinois, USA.
The phase 3 trial included 474 women aged 18–70 years (mean 51 years) receiving tamoxifen or aromatase inhibitors with or without gonadotropin-releasing hormone analogue therapy, all of whom were experiencing at least 35 moderate-to-severe vasomotor symptoms per week.
At baseline, the 316 patients who were randomly assigned to receive elinzanetant 120 mg/day for 52 weeks reported an average of 11.4 episodes per day in their hot flush daily diary, while the 158 patients who instead received placebo reported an average of 11.5 episodes per day.
After 4 weeks of treatment, the elinzanetant-treated women were experiencing 6.5 fewer daily episodes of moderate-to-severe vasomotor symptoms whereas those given placebo had an average of 3.0 fewer episodes, giving a significant least squares mean difference of 3.5 episodes.
And at week 12, the elinzanetant and control groups reported 7.8 and 4.2 fewer daily episodes, respectively, with a significant least squares mean difference of 4.2 episodes in favour of the neurokinin-targeted agent.
“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”, observe Fatima Cardoso (Champalimaud Clinical Center, Lisbon, Portugal) and co-authors.
The elinzanetant and placebo group participants both had “moderate sleep disturbance” at baseline based on their Patient Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b Total T scores of 60.6 and 60.7 points, respectively, where higher scores correspond to greater disturbance.
At week 12, the elinzanetant-treated patients reported a 10.6-point decrease versus a 4.1-point decrease in the controls, a significant difference in this key secondary endpoint, the researchers say.
In addition, the elinzanetant and placebo groups both scored 4.8 points out of a possible 8.0 points on the Menopause-Specific Quality of Life questionnaire at baseline, where higher scores equal greater impairment. After 12 weeks of treatment, the elinzanetant group had a 1.3-point improvement, significantly greater than the 0.5-point improvement in controls.
Over the first 12 weeks of treatment, one or more adverse events were reported by 69.8% of patients given elinzanetant and 62.0% of those given placebo. Those most common with elinzanetant treatment were headache, fatigue and somnolence. Serious adverse events were reported by a corresponding 2.5% and 0.6% of patients.
Five patients taking elinzanetant experienced an increase in liver enzymes, including one serious increase in aminotransferase levels, but all cases were reversible and “there did not appear to be a substantive hepatotoxicity signal”, the authors write.
Discussing their findings, Cardoso et al comment that “[a]lthough we did not collect data on treatment satisfaction in this trial, the observation that 91.6% of the participants who completed 52 weeks of treatment chose to continue receiving elinzanetant through an optional 2-year extension suggests a high level of satisfaction.”
Nevertheless, they admit that the study is limited by the subjective nature of the trial endpoints and the generalisabilty of the findings, given the predominantly White European ethnicity of the participants (88-89%).
Finally, although the trial was open to women undergoing prophylactic endocrine therapy, this applied to only one participant, leading the researchers to state that “conclusions regarding the efficacy of elinzanetant in this population cannot be drawn.”
Writing in an accompanying editorial, Ann Partridge (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) notes that the short follow-up of study was not designed to compare breast cancer outcomes between the study groups.
Nevertheless, she postulates that elinzanetant therapy “may affect these outcomes by reducing symptom burden and improving adherence to endocrine therapy”, adding that “elinzanetant appears to decrease levels of estradiol and progesterone in healthy premenopausal women.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2025 Springer Healthcare Ltd, part of Springer Nature
N Engl J Med 2025; doi:10.1056/NEJMoa2415566
N Engl J Med 2025; doi:10.1056/NEJMe2506475
https://pubmed.ncbi.nlm.nih.gov/40454634
https://pubmed.ncbi.nlm.nih.gov/40454644
Keywords: breast cancer, elinzanetant, vasomotor symptoms, endocrine therapy