Abstract PS5-02-15: Concurrent Trastuzumab Deruxtecan and Radiation Therapy in HER2- positive and HER2-low Metastatic Breast Cancer: Assessing the efficacy

Abstract Background: Metastatic breast cancer, particularly HER2-positive disease, remains a therapeutic challenge and is often associated with poor prognosis. While anti-HER2 therapies such as trastuzumab have improved outcomes, trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate, has shown promising efficacy even in heavily pretreated patients. Clinical trials, including DESTINY-Breast, have demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS). However, the safety and efficacy of combining T-DXd with radiotherapy (RT) have yet to be fully evaluated. This study aims to assess the outcomes of this combination in patients with HER2-positive and HER2-low metastatic breast cancer. Methods: We conducted a retrospective study including patients treated between November 2020 and January 2024. Patients with HER2-positive and HER2-low metastatic breast cancer who received concurrent trastuzumab der uxtecan and radiotherapy were identified. Data on patient demographics, treatment regimens, radiation doses, toxicity profiles, efficacy and treatment discontinuations were collected. Data on tumor response were collected through imaging examinations, and follow-up was conducted from the last day of radiotherapy until death or the last examination, and toxicities were graded using CTCAE V5.0. Results: The studied population includes 33 patients with HER2-positive and HER2-low metastatic breast cancer who underwent concurrent treatment with trastuzumab deruxtecan and radiotherapy. The median follow-up was 14 months. Treatment details indicated that trastuzumab deruxtecan was administered at the recommended dose across various treatment modalities. Of the patients evaluated, 39.4% achieved partial remis sion, while 9.1% attained complete remission. Additionally, 39.4% experienced stable disease, and 12.1% faced disease progression necessitating a change in therapy. Safety assessment revealed that acute toxicities were mainly associated with systemic treatment. Survival analysis showed 11 deaths (33.3%) during the follow-up period, with a median overall survival of 26 months and median progression-free survival of 12 months. Conclusion: The combination of trastuzumab deruxtecan with radiotherapy in HER2-positive and HER2-low metastatic breast cancer demonstrates promising efficacy with a manageable safety profile. Further studies are warranted to fully elucidate the potential synergistic effects of this treatment regimen and its impact on patient outcomes. Citation Format: J. BOUZIANE, P. Loap, S. Allali, L. Escalup, J. Pierga, Y. Kirova. Concurrent Trastuzumab Deruxtecan and Radiation Therapy in HER2- positive and HER2-low Metastatic Breast Cancer: Assessing the efficacy [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 PS5-02-15.