4CPS-081 Real-world effectiveness of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer

<h3>Background and Importance</h3> Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate with proven efficacy in HER2-positive metastatic breast cancer and, more recently, in HER2-low disease. However, real-world data on its effectiveness outside clinical trials are limited. Assessing clinical outcomes in daily practice is essential to confirm its benefit and optimise therapeutic strategies for unresectable or metastatic breast cancer. <h3>Aim and Objectives</h3> To evaluate the real-world effectiveness of T-DXd in patients with unresectable or metastatic breast cancer, including HER2-positive and HER2-low subgroups. Primary objectives were to assess progression-free survival (PFS) and overall survival (OS) and to compare outcomes between both indications. <h3>Material and Methods</h3> A retrospective observational study was conducted including patients with metastatic breast cancer treated with T-DXd for approved indications: (1) HER2-positive unresectable or metastatic breast cancer after at least one prior anti-HER2 regimen, and (2) HER2-low unresectable or metastatic breast cancer after previous chemotherapy. Variables included, obtained from Farmatools (v.3) Outpatient Module and medical records, were: sex, age, treatment indication, treatment start date and date of progression or death. Qualitative variables were expressed as frequencies and percentages; quantitative variables as mean±standard deviation or median (interquartile range). PFS and OS were estimated using the Kaplan–Meier method, and subgroup comparisons were performed with the log-rank test. Analyses were carried out using IBM-SPSS Statistics 28.0 for iOS. <h3>Results</h3> Thirty-one women were included (mean age 61.47±10.49 years); 15 (48.4%) had HER2-positive disease and 16 (51.6%) HER2-low disease. Median PFS was 5.0 months (95% CI: 3.66–6.35). By subgroup, median PFS was 10.0 months (95% CI: 6.02–13.98) in HER2-positive and 4.0 months (95% CI: 2.48–5.52) in HER2-low patients, with no statistically significant difference (p=0.336). Median OS was not estimable in either subgroup, and the comparison between indications showed no significant differences (p=0.930). However, patients treated in later therapy lines (&gt;3) had significantly longer OS than those treated in second–third lines (p = 0.024). <h3>Conclusion and Relevance</h3> In real-world practice, T-DXd demonstrated clinical activity in both HER2-positive and HER2-low metastatic breast cancer patients. Although no significant differences were observed between subgroups, later-line treatment was associated with improved survival. These findings support the effectiveness of T-DXd in a routine clinical setting and highlight the need for continued real-world evaluation to optimise patient outcomes. <h3>Conflict of Interest</h3> No conflict of interest