Efficacy and safety of trastuzumab deruxtecan in HR-negative HER2-low advanced breast cancer: A real-world, retrospective study.

e15019 Background: Trastuzumab deruxtecan (T-DXd) demonstrated promising efficacy in patients with HER2-low metastatic breast cancer (mBC), while most patients were hormone receptor (HR)-positive population. Limited data are available about its efficacy in HR-negative patients. We examined effectiveness and safety of T-DXd in HR-negative HER2-low mBC. Methods: This real-world, retrospective study included patients with pre-treated HR-negative HER2-low mBC who received at least one administration of T-DXd. The outcomes were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Results: From May 2022 and August 2024, a cohort of 50 patients were recruited, including 29 (58%) patients had primary HR-negative and 21 (42%) were converted by HR-positive disease. Eight (16%) patients were previously treated with anti trop-2 ADC, and 3 (6%) were treated with anti HER2 ADC. The median number of prior therapies for metastatic disease was 2 ( range 0–6). In the whole cohort, the ORR and DCR were 30% and 78%, and the median PFS and OS were 5.1 and 16.6 months. In subgroup analysis, patients with primary HR-negative mBC had the worse median PFS and OS compared with patients converted by HR-positive mBC, 3.8 versus 7.1 months, p = 0.002, and 11.9 versus 21.2 months, p = 0.02, respectively. Any-grade toxicity was registered in 44 (88%) patients. Most common AEs reported were nausea (68%), neutropenia (30%), and fatigue (36%). Grade 3/4 AEs were registered in 7 (14%) patients, including thrombocytopenia (10%), neutropenia (6%), leukopenia (6%), anemia (6%), drug-induced interstitial lung disease (2%), and nausea (2%). Conclusions: Efficacy and safety of T-DXd were confirmed in an unselected real-world population of HR-negative HER2-low mBC. These results are consistent with the results of known findings, and no new safety concerns were reported. Evaluation of efficacy. Treatment Response All patients(N=50) Primary HR-negative mBC(N=29) Converted by HR-positive mBC(N=21) ORR 15 (30.0) 6 (20.7) 9 (42.9) DCR 39 (78.0) 19 (65.5) 20 (95.2) Median PFS (95% CI) 5.1 (4.6-5.6) 3.8 (2.2-5.4) 7.1(1.7-12.5) Hazard ratio (95% CI) NA 2.76 (1.43-5.31) P value NA 0.002 Median OS (95% CI) 16.6 (10.8-22.4) 11.9 (6.7-17.1) 21.2 (12.4-30.0) Hazard ratio (95% CI) NA 3.49 (1.26-9.68) P value NA 0.02