Trial in Progress: HIGHLIGHT 1 – a study of fezolinetant in treatment-induced VMS
Celine Bouchard1, Kentaro Miyazaki2, Chun-Hang Tang3, Karla Martins3, Xuegong Wang4, Sonja Medley-Wilson4, Paula Briggs5
1Clinique RSF Inc., Quebec, Canada; 2Astellas Pharma Inc, Japan; 3Astellas Pharma Europe Ltd, UK; 4Astellas Pharma Inc, USA; 5Liverpool Women's Hospital, Liverpool Women's NHS Foundation Trust, Liverpool, UK

Objectives

•To assess the efficacy and safety of fezolinetant 45 mg once daily for treatment of moderate to severe vasomotor symptoms (VMS) in women with stage 0 to 3 hormone receptor-positive (HR+) breast cancer receiving adjuvant endocrine therapy
−Stage 0: cancer cells have not spread to nearby tissue
−Stage 3: cancer has spread from breast to lymph nodes near the breast or the chest wall

Introduction

Breast cancer is the most common cause of death due to malignant neoplasms in women globally, with approximately 2.3 million new cases in 20221
•Vasomotor symptoms (VMS) – hot flushes and night sweats – are a prominent side effect of adjuvant endocrine therapies (e.g., tamoxifen and aromatase inhibitors) used for treatment of breast cancer2 and can adversely affect patients’ quality of life (QoL) and treatment compliance3,4
•The pathophysiology of VMS in women undergoing cancer treatment is not fully elucidated but is hypothesised to have similar aetiology to VMS associated with menopause, i.e., rapid decline of oestrogen5
•Fezolinetant, an oral, nonhormonal, neurokinin 3 receptor antagonist, has demonstrated reductions in the frequency and severity of VMS associated with menopause,6,7 and has been approved in many regions, including North America, Europe, Asia, and Australia at a dose of 45 mg once daily8-13
•Fezolinetant works by blocking neurokinin B binding on the kisspeptin/neurokinin/dynorphin neuron, to restore normal sensitivity of the thermoregulatory centre in the hypothalamus to reduce the number and intensity of hot flashes and night sweats 6,7