In a phase III trial (OASIS-4) reported at the 2025 ASCO Annual Meeting and in The New England Journal of Medicine, Cardoso et al attempted to determine whether the neurokinin-targeted therapy elinzanetant reduced the risk of vasomotor symptoms from endocrine therapy for patients with hormone receptor (HR)-positive breast cancer.
Study Details
In the double-blind international trial, 474 women with moderate-to-severe vasomotor symptoms associated with endocrine therapy for HR-positive breast cancer or its prevention were randomly assigned 2:1 between October 2022 and November 2024 to receive elinzanetant at 120 mg once daily for 52 weeks (n = 316) or once-daily placebo for 12 weeks followed by once-daily elinzanetant at 120 mg for 40 weeks. The primary outcome measures were change in the mean daily frequency of moderate-to-severe vasomotor symptoms from baseline to week 4 and baseline to week 12 (placebo period in the placebo-elinzanetant group).
Key Findings
At baseline, the mean daily frequency of moderate-to-severe vasomotor symptoms was 11.4 episodes (95% confidence interval [CI] = 10.7–12.2) in the elinzanetant group and 11.5 episodes (95% CI = 10.5–12.5) in the placebo-elinzanetant group.
At week 4, the mean change from baseline in the mean daily frequency of moderate-to-severe vasomotor symptoms was −6.5 episodes (95% CI = −7.2 to −5.8) among patients receiving elinzanetant vs −3.0 episodes (95% CI = −3.9 to −2.2) among those receiving placebo (least-squares mean difference = −3.5 episodes, 95% CI = −4.4 to −2.6, P < .001).
At week 12, the mean change was −7.8 episodes (95% CI = −8.5 to −7.1) among those receiving elinzanetant vs −4.2 episodes (95% CI = −5.2 to −3.2) among those receiving placebo (least-squares mean difference = −3.4 episodes, 95% CI = −4.2 to −2.5, P < .001).
From weeks 1 through 12, 69.8% of patients in the elinzanetant group and 62.0% of those receiving placebo had an adverse event of any grade; the most common were headache (9.5% vs 12.7%), somnolence (10.8% vs 3.8%), arthralgia (6.3% vs 6.3%), nausea (6.0% vs 6.3%), and diarrhea (5.1% vs 1.9%). Grade ≥ 3 adverse events occurred in 4.1% vs 2.5% of patients, and serious events occurred in 2.5% vs 0.6%.
The investigators concluded: “Elinzanetant led to a significantly lower frequency of vasomotor symptoms associated with endocrine therapy than placebo.”
Fatima Cardoso, MD, of the Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Bayer. For full disclosures of all study authors, visit The New England Journal of Medicine.
