Abstract PS1-01-11: Outcomes and Toxicity of Combination Chemotherapy and HER2-Targeted Therapy Versus HER2-Targeted Therapy Alone in Elderly Patients with HER2-Positive Breast Cancer

Abstract Background: The optimal approach for treating elderly patients (age ≥70) with HER2-positive breast cancer is uncertain, especially when balancing the benefits of combination chemotherapy with HER2-targeted agents versus targeted therapy alone. Given the increased risk of treatment-related toxicities in older adults, it is crucial to understand real-world outcomes and risks associated with these regimens in this population. Methods: We conducted a retrospective, real-world cohort study using the TriNetX platform. We identified two cohorts of patients aged ≥70 years with HER2-positive breast cancer. Cohort A (n=4,178) included patients who received HER2-targeted therapy (trastuzumab or trastuzumab deruxtecan) without concurrent chemotherapy (excluding docetaxel/paclitaxel). Cohort B (n=7,607) included those treated with HER2-targeted therapy in combination with chemotherapy (docetaxel or paclitaxel). Propensity score matching was performed, yielding 3,595 patients per cohort for comparative analyses. Outcomes were assessed with Kaplan-Meier survival curves and hazard ratios (HR) for mortality and major toxicities. Results: After 1:1 propensity score matching, 3,595 patients were included in each cohort. Mortality was slightly higher in the HER2-only group (25.96%) compared to the combination group (23.91%) (HR 1.136, 95% CI: 1.036-1.247, p=0.007). Hospitalization occurred more frequently in the combination group (36.2%) compared to the HER2-only group (30.3%; HR 0.830, 95% CI: 0.749-0.919, p=0.001). Outpatient visits were more frequent in the HER2-only group (56.1% vs. 32.6%; HR 1.649, 95% CI: 1.072-2.537, p=0.016). Rates of cancer progression were similar between groups (24.6% combination vs. 23.8% HER2-only; HR 1.004, p=0.951). Cardiomyopathy was more frequent in the combination group (12.7% vs. 10.4%; HR 0.834, p=0.012), while heart failure showed a non-significant trend towards higher frequency in the combination group (15.5% vs. 13.6%; HR 0.886, p=0.060). Treatment-related toxicities were consistently higher in the combination group, including neutropenia (16.3% vs. 6.0%; HR 0.359, p