Abstract

Abstract Background: Trastuzumab Deruxtecan (T-DXd) is an antibody-drug conjugate originally approved for use in patients with HER2–positive metastatic breast cancer (MBC). In June 2022, data from the DESTINY-Breast04 trial revealed a near-doubling of progression-free survival (PFS) and significantly improved overall survival (OS) for patients with HER2-low MBC (immunohistochemistry [IHC] grade 1+ or IHC2+ in situ hybridization [ISH]-negative) treated with T-DXd versus standard-of-care chemotherapy. The data from this clinical trial led to the approval of T-DXd for use in patients with HER2-low MBC. However, the DESTINY-Breast studies completed to date have included < 5% black patients. This retrospective study of patients at a racially diverse NCI Comprehensive Cancer Center was designed to study whether T-DXd in a real-world population are comparable to published data. Methods: A retrospective chart review was conducted and identified 72 patients with HER2-low and HER2-positive MBC who received T-DXd between December 2019 and March 2023 at the Winship Cancer Institute at Emory University. Data collected for all patients included demographics, prior breast cancer history, T-DXd -specific and post-T-DXd treatment, and clinical outcomes where applicable. Results: Of the 103 patients who were dosed with T-DXd, 55 (53.4%) had HER2-positive disease, and 48 (46.7%) patients had HER2-low disease. 71 (68.9%) patients had hormone-receptor positive disease and 32 (31.1%) patients had hormone-receptor negative disease. The overall study population was 46% Caucasian; 38% African American; 13% Asian; 4% Unreported. The average number of cycles received was 11 (on treatment an average of 8 months). Pneumonitis occurred in 5 patients (4.9%). HER2-positive patients were typically on T-Dxd for a greater number of cycles than HER2-low patients (Table 1). Additionally, patients with brain metastases were, on average, treated with T-Dxd longer than patients without brain metastases, 14.5 versus 9 cycles. The number of cycles of T-Dxd received, the need for dose reduction, and incidence pneumonitis did not differ significantly between black and white patients. The data for this study is preliminary 48% of the patient population are still actively undergoing T-Dxd treatment. Conclusion: This study reviewed and analyzed T-Dxd treatment in a diverse population of both HER2-positive and HER2-low MBC patients, and in this study, outcomes of treatment did not differ by race. More attention to this topic is needed in future studies of larger populations, along with increased efforts to enroll diverse patient populations in clinical trials. Table 1. Citation Format: Jane Meisel, Maisey Ratcliffe. Real-World Experience with Trastuzumab Deruxtecan at a Diverse NCI Comprehensive Cancer Center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-16-09.

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