Outcomes with trastuzumab deruxtecan by biomarker status, line of treatment and prior receipt of sacituzumab govitecan in a large real-world database of patients with metastatic breast cancer
Paolo Tarantino, David Lee, Julia Foldi, Pamela R. Soulos, Cary P. Gross, Thomas Grinda, Eric P. Winer, Nancy U. Lin, Ian E. Krop, Sara M. Tolaney, Maryam B. Lustberg, Sarah Sammons
Abstract
BACKGROUND: Most of the published data with trastuzumab deruxtecan (T-DXd) derive from clinical trials with selected populations and little representation of US patients. Limited real-world data are available. PATIENTS AND METHODS: Using a nationwide electronic health record-derived database, we identified patients with metastatic breast cancer (MBC) who initiated T-DXd between December 2019 and September 2023. Tumors were categorized as human epidermal growth factor receptor 2 (HER2)-positive if positive at any time before starting T-DXd and HER2-negative if never HER2-positive before T-DXd. Hormone receptor (HR) status was derived from the last biopsy before T-DXd initiation. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Overall, 1490 patients were included: 884 with HER2-positive, 487 with HR-positive/HER2-negative, and 119 with HR-negative/HER2-negative (triple-negative) MBC. Median age was 59 years (range 23-84 years), and median prior lines of systemic treatments were 3 and 4 for HER2-positive and HER2-negative MBC, respectively. rwPFS and OS were 12.3 and 24.6 months for HER2-positive disease; 7.6 and 15.5 months for HR-positive/HER2-negative disease; and 4.3 and 10.4 months for triple-negative disease. T-DXd use in earlier lines of treatment was associated with significantly longer rwPFS in HER2-positive (P = 0.02), but not in HR-positive/HER2-negative MBC (P = 0.07). Among patients with triple-negative disease pretreated with sacituzumab govitecan (SG, n = 58), after adjusting for prior lines of treatment, shorter rwPFS (3.4 versus 5.7 months, P = 0.009) and OS (9.0 versus 14.5 months, P = 0.002) were observed compared with patients without prior SG (n = 61). rwPFS with T-DXd was also significantly shorter in patients with BRCA mutations (7.8 versus 9.2 months, P = 0.02) and numerically shorter in patients with programmed death-ligand 1-negative disease (6.9 versus 12.6 months, P = 0.31). CONCLUSIONS: In a large dataset, T-DXd showed favorable activity for treating MBC, although outcomes for HER2-positive disease appeared worse than those observed in clinical trials. Prior SG treatment was associated with inferior outcomes with T-DXd, suggesting cross-resistance between these antibody-drug conjugates.