Elinzanetant for Vasomotor Symptoms from Endocrine Therapy for Breast Cancer

Cardoso, Fatima M.D.
Parke, Susanne M.D.
Brennan, Donal J. M.B., Ph.D.
Briggs, Paula M.B., Ch.B.
Donders, Gilbert M.D.
Panay, Nick F.R.C.O.G.
Haseli-Mashhadi, Nazanin M.Sc.
Block, Michael Ph.D.
Caetano, Cecilia M.D.
Francuski, Maja M.D.
Haberland, Claudia Ph.D.
Laapas, Kaisa M.Sc.
Seitz, Christian M.D.
Zuurman, Lineke M.D.

¹Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal
²ABC Global Alliance, Lisbon, Portugal
³Bayer, Berlin
⁴University College Dublin Gynaecological Oncology Group, UCD School of Medicine, Mater Misericordiae University Hospital, Dublin
⁵Liverpool Women's Hospital, Liverpool, United Kingdom
⁶Department of Clinical Research for Women, Femicare, Tienen, Belgium
⁷Department of Obstetrics and Gynecology, University Hospital, University of Antwerp, Antwerp, Belgium
⁸Queen Charlotte's and Chelsea Hospital, Imperial College London, London
⁹Bayer, Reading, United Kingdom
¹⁰Bayer, Leverkusen, Germany
¹¹Bayer, Basel, Switzerland
¹²Bayer, Espoo, Finland
¹³Charité-Universitätsmedizin Berlin, Berlin

Dr. Cardoso can be contacted at [email protected].

This article was published on June 2, 2025, and updated on June 5, 2025, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Supported by Bayer.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

New England Journal of Medicine 393(8):p 753-763, August 21, 2025. | DOI: 10.1056/NEJMoa2415566

ABSTRACT

BACKGROUND

Women receiving endocrine therapy for hormone receptor (HR)-positive breast cancer or its prevention among those at high risk for breast cancer commonly have vasomotor symptoms. Data are lacking on the effects of elinzanetant, a neurokinin-targeted therapy shown to be effective in treating vasomotor symptoms, in this population.

METHODS

We performed a phase 3 trial involving women 18 to 70 years of age with moderate-to-severe vasomotor symptoms associated with endocrine therapy for HR-positive breast cancer or its prevention. Women were randomly assigned in a 2:1 ratio to receive once-daily elinzanetant at a dose of 120 mg for 52 weeks or once-daily placebo for 12 weeks followed by once-daily elinzanetant at a dose of 120 mg for 40 weeks. The primary end points were the change in the mean daily frequency of moderate-to-severe vasomotor symptoms from baseline to week 4 and to week 12.

RESULTS

A total of 316 participants were assigned to the elinzanetant group and 158 to the placebo-elinzanetant group. At baseline, the mean daily frequency of moderate-to-severe vasomotor symptoms was 11.4 episodes (95% confidence interval [CI], 10.7 to 12.2) in the elinzanetant group and 11.5 episodes (95% CI, 10.5 to 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 those who were receiving elinzanetant and -3.0 episodes (95% CI, -3.9 to -2.2) among those who were receiving placebo (least-squares mean difference, -3.5 episodes; 95% CI, -4.4 to -2.6; P<0.001). At week 12, the mean change was -7.8 episodes (95% CI, -8.5 to -7.1) among those receiving elinzanetant and -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<0.001). During weeks 1 through 12, a total of 220 participants (69.8%) receiving elinzanetant and 98 (62.0%) receiving placebo reported at least one adverse event that occurred while receiving elinzanetant or placebo, with the most common being headache, fatigue, and somnolence. Serious adverse events occurred during weeks 1 through 12 in 8 participants (2.5%) receiving elinzanetant and 1 participant (0.6%) receiving placebo.

CONCLUSIONS

Elinzanetant led to a significantly lower frequency of vasomotor symptoms associated with endocrine therapy than placebo. (Funded by Bayer; OASIS-4 ClinicalTrials.gov number, NCT05587296.)

Elinzanetant for Symptoms from Endocrine Therapy

In this trial involving women taking endocrine therapy for HR-positive breast cancer, elinzanetant (a neurokinin-targeted therapy) significantly reduced the frequency of moderate-to-severe vasomotor symptoms.