Using Elinzanetant to Manage Hot Flashes in Breast Cancer Patients Treated with Endocrine Therapy
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on September 17th, 2025
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For patients with hormone receptor–positive breast cancer, endocrine therapy is typically prescribed for five to ten years. While effective, this prolonged treatment often causes vasomotor side effects, most notably hot flashes, which tend to be more severe in younger patients who have not yet experienced menopause. With funding from Bayer, a study was conducted to evaluate the effectiveness of elinzanetant in reducing hot flashes during breast cancer treatment.
The phase 3 clinical trial enrolled 474 women with a mean age of 51 years who had been diagnosed with hormone receptor–positive breast cancer. Most cases were detected at an early stage, with 50% at stage I and 40% at stage II. Approximately half of the participants were receiving tamoxifen, while the other half were on aromatase inhibitors. On average, the women had been undergoing endocrine therapy for about 20 months prior to the trial.
Participants were randomized to receive either 120 mg of elinzanetant once daily or placebo. Elinzanetant is a small-molecule antagonist that blocks NK-1 and NK-3 receptors. When estrogen activity declines naturally during menopause—or is artificially suppressed by endocrine therapy—KNDy neurons expressing NK-1 and NK-3 become hyperactive, disrupting thermoregulation and triggering hot flashes. By blocking this signaling pathway, elinzanetant aims to restore balance and reduce vasomotor symptoms.
After 12 weeks of treatment, elinzanetant demonstrated strong efficacy in controlling hot flashes. Patients receiving the drug reported fewer and less severe episodes, along with improvements in other symptom-related measures, including the MENQOL score. Currently, only two nonhormonal therapies are FDA-approved for vasomotor symptoms: paroxetine and fezolinetant. However, paroxetine is contraindicated in patients treated with tamoxifen, and evidence supporting fezolinetant’s effectiveness remains limited. These findings suggest that, pending further validation, elinzanetant may offer an important new nonhormonal option for managing hot flashes in breast cancer patients undergoing endocrine therapy.
The phase 3 clinical trial enrolled 474 women with a mean age of 51 years who had been diagnosed with hormone receptor–positive breast cancer. Most cases were detected at an early stage, with 50% at stage I and 40% at stage II. Approximately half of the participants were receiving tamoxifen, while the other half were on aromatase inhibitors. On average, the women had been undergoing endocrine therapy for about 20 months prior to the trial.
Participants were randomized to receive either 120 mg of elinzanetant once daily or placebo. Elinzanetant is a small-molecule antagonist that blocks NK-1 and NK-3 receptors. When estrogen activity declines naturally during menopause—or is artificially suppressed by endocrine therapy—KNDy neurons expressing NK-1 and NK-3 become hyperactive, disrupting thermoregulation and triggering hot flashes. By blocking this signaling pathway, elinzanetant aims to restore balance and reduce vasomotor symptoms.
After 12 weeks of treatment, elinzanetant demonstrated strong efficacy in controlling hot flashes. Patients receiving the drug reported fewer and less severe episodes, along with improvements in other symptom-related measures, including the MENQOL score. Currently, only two nonhormonal therapies are FDA-approved for vasomotor symptoms: paroxetine and fezolinetant. However, paroxetine is contraindicated in patients treated with tamoxifen, and evidence supporting fezolinetant’s effectiveness remains limited. These findings suggest that, pending further validation, elinzanetant may offer an important new nonhormonal option for managing hot flashes in breast cancer patients undergoing endocrine therapy.