644eP Fertility counselling, preservation and reproductive outcomes in young women with breast cancer: A single-center cohort study

Background: Trastuzumab deruxtecan (T-DXd) has reshaped treatment of HER2positive and HER2-low advanced breast cancer (ABC), yielding substantial survival gains.Across the DESTINY-Breast trials, nausea and vomiting (NV) were among the most common adverse events with T-DXd, showing a pattern distinct from conventional cytotoxic chemotherapeutic agents, characterized by persistent, long-delayed nausea extending beyond the typical 5-day window.Antiemetic use in the DESTINY trials was not protocol-standardized, likely contributing to the high NV incidence and the subsequent classification of T-DXd as moderately-to-highly emetogenic.Few prospective studies have evaluated antiemetics for preventing T-DXd-related NV, including long-delayed NV.This study addresses this gap by prospectively assessing the efficacy and safety of NEPA (fixed combination of netupitant, an NK 1 receptor antagonist (RA), and palonosetron, a second-generation 5-HT 3 RA) for NV prevention in patients with HER2-positive or HER2-low ABC receiving T-DXd in real-world practice.Trial design: This is a prospective, observational, multi-center, single-arm study in Korea, enrolling 100 adults with ABC initiating T-DXd.Patients are followed until discontinuation of T-DXd or 8 cycles, with antiemetic efficacy uniquely assessed over the full 21-day cycle.Single dose oral NEPA plus dexamethasone are administered 1 hour prior to T-DXd.Complete response (CR: no emesis, no rescue medication) is assessed during the acute (0-24 h), delayed (>24-120 h), overall (0-120 h), longdelayed (>120-504 h), and extended overall (0-504 h) phases following T-DXd administration.The primary endpoint is CR during the long-delayed phase of cycles 1-2.Secondary endpoints include complete control, total control, no nausea, no significant nausea, rescue use, T-DXd dose alterations and discontinuations, quality-oflife outcomes, fatigue occurrence and severity, and adverse events.As of January 2026, 18 patients were enrolled.Study completion is expected in 4Q 2026.