Astellas Pharma Inc. has commenced the HIGHLIGHT 1 Phase 3 clinical trial to investigate fezolinetant for the treatment of moderate to severe vasomotor symptoms (VMS), commonly known as hot flashes and night sweats, in women with breast cancer undergoing adjuvant endocrine therapy. This randomized, double-blind, placebo-controlled study aims to address a significant unmet need, as there are currently no approved treatments for VMS specifically for this patient population.
The HIGHLIGHT 1 trial (NCT06440967) plans to enroll approximately 540 participants with stage 0 to 3 hormone receptor-positive breast cancer across up to 100 sites globally. Participants will be randomized 1:1 to receive either fezolinetant or a placebo. The co-primary endpoints will assess the change in frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12. Patients will receive treatment for 52 weeks, with a final evaluation at 55 weeks.
The Need for New VMS Treatments in Breast Cancer
Breast cancer is the most prevalent cancer among women worldwide, with approximately 2.3 million new cases reported in 2022. Adjuvant endocrine therapies, such as tamoxifen and aromatase inhibitors, are used to treat approximately 77% of breast cancers. However, these therapies often induce VMS, affecting up to 97% of patients, which can significantly impair their quality of life and adherence to treatment.
Marci English, Vice President, Head of BioPharma Development at Astellas, emphasized the importance of this research, stating, "VMS can adversely affect quality of life, as well as compliance with treatment, for patients with breast cancer taking adjuvant endocrine therapy. We are excited to get the HIGHLIGHT 1 study underway, as currently there are no approved treatments for moderate to severe VMS that can be used by these patients."
Fezolinetant: A Novel Nonhormonal Approach
Fezolinetant is an investigational oral, nonhormonal medicine designed to alleviate VMS by targeting neurokinin B (NKB) binding on the kisspeptin/neurokinin/dynorphin (KNDy) neuron. This mechanism helps to re-establish equilibrium in the brain's temperature control center (hypothalamus), potentially reducing the frequency and intensity of hot flashes and night sweats. The drug has already been approved by the FDA for treating hot flashes caused by menopause.
Trial Design and Endpoints
The HIGHLIGHT 1 trial is designed to evaluate both the efficacy and safety of fezolinetant in this specific patient population. The primary endpoints focus on the change in VMS frequency and severity, while secondary endpoints include monitoring treatment-emergent adverse events, laboratory value abnormalities, and vital sign changes. The study also includes assessments of mammogram or breast ultrasound abnormalities and pharmacokinetic parameters.
Prior Research and Safety Profile
Previous studies, such as the DAYLIGHT clinical trial, have indicated positive safety and efficacy data for fezolinetant in managing moderate to severe VMS in menopausal women for whom hormone therapy was not recommended. Common adverse events reported in these trials included headache and COVID-19. However, potential severe side effects, such as increased liver blood test abnormalities, have also been noted, warranting careful monitoring during the HIGHLIGHT 1 trial.
Implications for Breast Cancer Treatment
If successful, the HIGHLIGHT 1 trial could provide a much-needed treatment option for women with breast cancer experiencing VMS due to adjuvant endocrine therapy. By improving symptom management, fezolinetant has the potential to enhance patients' quality of life and adherence to essential cancer treatments.
