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Neurokinin pathway antagonists for vasomotor symptoms in women with breast cancer: focus on elinzanetant and fezolinetant

par Pogoda, Katarzyna;Arecco, Luca ;Lambertini, Matteo Md Phd M.
Référence Breast, 88, 104812
Publication Publié, 2026-08

Article révisé par les pairs

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Résumé :

Vasomotor symptoms (VMS) have a major impact on quality-of-life in women with hormone receptor–positive breast cancer receiving adjuvant endocrine therapy. As menopause hormone therapy is contraindicated in this setting, effective non-hormonal treatment options are urgently needed. We performed a focused narrative review of neurokinin (NK) receptor antagonists for VMS, including the OASIS-1-4 program for elinzanetant and the SKYLIGHT, MOONLIGHT, and DAYLIGHT programs for fezolinetant, with emphasis on breast cancer–specific data, safety, drug-drug interactions, and selected special populations relevant to oncology practice. Elinzanetant, a dual NK1/NK3 receptor antagonist approved by the European Medicines Agency and the U.S. Food and Drug Administration, provides the first phase III evidence in the specific cohort of patients with breast cancer receiving endocrine therapy. In the OASIS-4 trial, elinzanetant demonstrated rapid and clinically meaningful reductions in moderate-to-severe VMS, with sustained improvements in sleep and menopause-specific quality of life and a favorable tolerability profile without a signal for clinically significant hepatotoxicity. Fezolinetant, a selective NK3 receptor antagonist approved for menopausal VMS in the general population, has shown robust efficacy across multiple phase III trials; however, its use requires liver function monitoring due to hepatotoxicity, and its role in breast cancer survivors remains under investigation. Safety considerations of NK receptor antagonists include their use alongside CDK4/6 inhibitors. With breast cancer–specific data for elinzanetant and ongoing trials of fezolinetant, these agents will change clinical practice by improving symptom control and adherence to adjuvant endocrine therapy overall.