Background
The approval of trastuzumab deruxtecan (T-DXd) has transformed treatment for HER2-low/ultralow metastatic breast cancer. However, real-world data regarding treatment patterns and effectiveness remains limited, particularly in community settings. This study evaluated T-DXd use and outcomes across US community oncology clinics.
Methods
Retrospective study using structured and unstructured electronic health record data from ONCare Alliance. Eligible patients received T-DXd for treatment of HER2-low metastatic breast cancer. Baseline characteristics, overall response rate, and time-to-event outcomes from T-DXd initiation were analyzed with descriptive statistics and Kaplan-Meier methods, using log-rank and chi-square tests of group differences. Results were stratified by hormone receptor (HR) status, prior chemotherapy, and presence of brain metastases.
Results
Median age among 300 randomly sampled patients (77.0% HR–positive [HR+]; 23.0% HR-negative [HR–]) was 65 years, and 79.7% were White. One-fourth (24.7%) had de novo metastatic breast cancer, 22.7% had ECOG performance status of 2 or more, and 39.3% had 1 or more comorbidity. Most patients received T-DXd monotherapy (87.3%). Baseline characteristics were similar by HR status, but HR+ patients received T-DXd in later lines (3 lines or more: 88.7% HR+ and 53.6% HR–). Median follow-up was 12.1 months (13.1 months HR+ and 10.0 months HR–). Median real-world progression-free survival (rwPFS) was 7.4 months (7.7 months HR+ and 4.9 months HR–). The 12-month overall survival (OS) was 62% (64% HR+ and 55% HR–). Real-world overall response rate was 56.3% (56.4% HR+ and 56.0% HR–). Among patients who were HR+, T-DXd showed greater effectiveness in HR+ chemotherapy-naive (n = 41) compared with HR+ non-chemotherapy-naive (n = 190): rwPFS was 10.2 vs 7.4 months and 12-month OS was 74% vs 62% (P < .05 for both). rwPFS was numerically similar in patients with brain metastases (n = 40) vs those without (n = 260): 6.3 vs 7.5 months (P = .07) (Table).
Conclusions
T-DXd demonstrated favorable effectiveness in real-world community oncology patients with HR+ and HR– HER2-low mBC, despite this population appearing older, frailer, and more heavily pretreated than typical clinical trial patients. These findings support the use of T-DXd across diverse clinical settings.
