Safety and Cardiovascular Considerations of Novel Non-Hormonal VMS Therapies

This episode, titled "Safety and Cardiovascular Considerations of Novel Non-Hormonal VMS Therapies," features panelists conducting a detailed review of the safety data for the two newest FDA-approved non-hormonal treatments for VMS — fezolinetant and elinzanetant — with a particular focus on hepatic monitoring, cardiovascular safety, and practical clinical application.

Dr. Kristi DeSapri begins with fezolinetant, noting that post-approval data identified liver function abnormalities in approximately 2% of patients, including elevations in AST, ALT, and bilirubin. Current recommendations call for liver function testing at baseline, monthly for the first three months, and again at six and nine months. Women with pre-existing elevated liver function tests are considered poor candidates for this medication class, and clinicians are advised to monitor for symptoms such as right upper quadrant pain, jaundice, unexplained fatigue, and diarrhea, as well as potential drug interactions that may affect metabolism.

For elinzanetant, liver function elevations were observed at a lower rate of approximately 0.6% in the OASIS 1 and 2 clinical trials. Similar baseline and three-month monitoring is recommended, along with routine symptom assessment at follow-up visits. General side effects for both agents, including gastrointestinal symptoms and headache, are noted as consistent with those reported in their respective package inserts.

Dr. Erin Michos then addresses cardiovascular safety, highlighting that women with cardiovascular disease were not excluded from the elinzanetant trials. Notably, data trends suggested a reduction in both blood pressure and cortisol levels with elinzanetant, pointing toward a potentially favorable vascular profile. No excess cardiovascular events were observed in either trial, leading the cardiologist to express confidence in recommending these agents for patients with VMS who carry unacceptably high cardiovascular risk for hormone therapy. Both panelists note that trial populations included women aged 40 to 65 — with an average age of 52 to 54 — providing clinically relevant evidence for the population most commonly presenting with VMS.

In the next episode, "Elinzanetant for VMS in Breast Cancer Patients: Insights from the OASIS-4 Trial," panelists will discuss the clinical significance of the OASIS-4 study, which specifically evaluated elinzanetant for VMS management in women with a history of breast cancer on adjuvant therapy, highlighting its potential as a game-changing non-hormonal option for this underserved patient population.