Can the new drug Fezolinetant relieve hot flashes in women with hormone-receptor-positive breast cancer who are undergoing anti-hormone therapy?

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue characterized by the uncontrolled proliferation of mammary gland cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the stage of the disease, the tumor’s growth rate (Ki-67 index), the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased presence of HER2 receptors on the cells (HER2-positive). If hormone receptors are detected on the cancer cells, anti-hormone therapy is a core component of treatment. This therapy aims to inhibit the growth of hormone-dependent tumor cells by inducing a drug-induced estrogen deficiency. However, the resulting estrogen deficiency not only affects the tumor but can also cause symptoms similar to the hormonal changes experienced during menopause—such as hot flashes.

The standard treatment for hot flashes during menopause is hormone replacement therapy; however, this cannot be administered to breast cancer patients because it may increase the risk of recurrence. The drug fezolinetant could offer an alternative. Fezolinetant is a neurokinin-3 receptor antagonist that is not a hormonal agent; rather, it acts on specific receptors in the brain, thereby restoring balance to the brain’s temperature control center. This reduces hot flashes. The drug is already approved for the treatment of hot flashes associated with menopause—but not yet for use in conjunction with anti-hormone therapy in breast cancer patients.

The goal of this Phase 3 study is to investigate whether fezolinetant can reduce the frequency and severity of hot flashes in the context of anti-hormone therapy. To this end, patients will be randomly assigned to two groups. Group 1 receives the study drug fezolinetant, and Group 2 receives a placebo (a drug without an active ingredient). The study is double-blind, meaning that neither the medical staff nor the patients know which drug is being administered. Fezolinetant and the placebo are taken once a day as a tablet for a total of 52 weeks, and a follow-up appointment is scheduled every 4 weeks. Three weeks after the end of treatment, a final evaluation of the treatment takes place, and a total of two additional follow-up visits are scheduled up to 2 years after the start of participation. Patients receive an electronic device with an app that allows them to record their hot flashes daily and answer questions. In some cases, the app can also be installed directly on the patient’s own smartphone. The effectiveness of the therapy is initially measured 4 and 12 weeks after the start of the study. To do this, the frequency of hot flashes is compared to that before the start of the study.

Women aged 18 and older with hormone receptor-positive breast cancer who are receiving anti-hormone therapy as adjuvant therapy and experience at least 7 moderate to severe hot flashes per day are eligible to participate in this study. The disease must not have metastasized (no distant metastases; corresponding to stages 0–3). The anti-hormone therapy (tamoxifen or an aromatase inhibitor, with or without GnRH agonists/antagonists) must have remained unchanged for at least 4 months and must not be altered during study participation.