Managing trastuzumab deruxtecan-related adverse events in patients with metastatic breast cancer: insights from a worldwide survey of the Hermione EDUcational project

PURPOSE: Trastuzumab deruxtecan (T-DXd) has shown remarkable efficacy in phase III trials in patients with HER2-positive early- and late-stage breast cancer and HER2-low/ultra-low metastatic breast cancer (mBC). However, toxicities remain prevalent and clinically relevant, leading to dose reductions/interruptions or discontinuation. METHODS: A survey was conducted across oncologists in 13 countries worldwide to collect experiences in managing T-DXd-related toxicities, focusing on nausea/vomiting, fatigue, and interstitial lung disease (ILD) as key areas of clinical concern. RESULTS: Ninety-nine experts participated in the survey. Nausea and fatigue were the most common toxicities, reported by 91.9% and 94.9% of respondents, respectively. 5-HT3 receptor antagonists, NK1 receptor antagonists, and corticosteroids were "very often" prescribed for prophylaxis. The frequency of use of second‑generation 5‑HT3 receptor antagonists varied among respondents. Most frequently, they employed an NK1 receptor antagonist combined with corticosteroids and 5‑HT3 receptor antagonists. Forty-four percent of respondents prescribed 4‑drug regimens incorporating NK1 receptor antagonists and olanzapine to all patients with nausea/vomiting above grade 1 in the first cycle, 35% reserved them for high‑risk patients, and 21% used them for all patients from cycle one. For all respondents, patients receiving T‑DXd experienced fatigue, with 65% observing it in more than 60% of patients, and most considered nausea/vomiting and fatigue to moderately or significantly affect daily activities and quality of life. ILD was reported as rare or occasional and was generally monitored using computed tomography. CONCLUSION: Real-life management of T-DXd-related toxicities is complex and needs an ongoing comprehensive evaluation of patients before, during and after therapy, with a highly trained/skilled multidisciplinary team.