Abstract PS5-01-28: Us real-world clinical outcomes of tucatinib, trastuzumab, and capecitabine following trastuzumab deruxtecan for the treatment of her2+ metastatic breast cancer

Abstract Background: US and EU treatment guidelines currently recommend tucatinib in combination with trastuzumab and capecitabine (TTC) in third-line (3L) for patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC), and in second-line (2L) for those patients with brain metastases (BM). More recently, trastuzumab deruxtecan (T-DXd) has become the recommended 2L treatment option and may be considered as first-line treatment for patients with rapid progression after (neo)adjuvant therapy. Previous real-world studies in patients receiving TTC after T-DXd have reported median time to next treatment (TTNT) of 6 months and median overall survival (OS) of 13 months; however, these study populations included later line treatment, a small sample size, and did not solely include TTC immediately following T-DXd, limiting applicability to current clinical practice. This study aimed to describe real-world outcomes in patients with HER2+ MBC in the US who were treated with TTC in 2L, 3L and fourth-line (4L) immediately following T-DXd. Methods: We conducted a retrospective cohort analysis of patients with HER2+ MBC receiving TTC therapy using the Flatiron Health electronic health record (EHR)-derived deidentified longitudinal database. This US nationwide database, containing patient-level structured and unstructured data curated using natural language processing with machine learning and technology-enabled abstraction, includes >720,000 patients with breast cancer. Patients included were diagnosed with HER2+ MBC (January 2017 to July 2024), treated with TTC in 2L, 3L or 4L immediately following T-DXd, and were not enrolled in clinical trials. Patients were assessed from the start of TTC (index date) to death, last medical activity, or end of available study follow-up (January 2025), whichever came first. Primary outcomes included, but were not limited to, TTNT and OS in all patients. Exploratory analyses will assess TTNT and OS in patients stratified by BM status, duration of T-DXd treatment, and hormone receptor status. Descriptive statistics were used for patient characteristics, and outcomes were evaluated using Kaplan-Meier analyses. Results: In total, 92 patients with HER2+ MBC received TTC immediately following T-DXd. Overall, median (95% CI) TTNT was 8.6 (5.7-11.6) months and median (95% CI) OS was 19.5 (12.0-26.1) months (Table). Exploratory outcomes will be presented in future analyses. Conclusion: Patients with HER2+ MBC benefit from TTC immediately after treatment with T-DXd, demonstrating its clinically meaningful activity in a contemporaneous post-T-DXd setting. These results reinforce the effectiveness of tucatinib, with longer TTNT and OS than in previous real-world studies, in a population more applicable to current clinical practice. Citation Format: J. Chien, E. Neuberger, S. Simon, K. Watkins, G. Curigliano, B. Li, S. Stergiopoulos, M. Czachorowski, H. Itakura. Us real-world clinical outcomes of tucatinib, trastuzumab, and capecitabine following trastuzumab deruxtecan for the treatment of her2+ metastatic breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-01-28.