279 - Safety and Efficacy of Combined Trastuzumab-Deruxtecan and Concurrent Radiation Therapy in Breast Cancer: The TENDANCE Multicentric French Study (Trastuzumab-Deruxtecan and Concurrent Radiation Therap

K. Debbi¹, M. A. Benderra², J. Medioni³, C. Durdux⁴, B. Asmahane⁵, L. Monnier⁶, J. Gligorov⁷, E. Assaf⁸, and Y. Belkacemi⁹; ¹APHP. Radiation Oncology Department and Henri Mondor Breast Center. Henri Mondor University Hospital. University of Paris East Creteil (UPEC). INSERM U955 (i-Biot), IMRB, Créteil, France., Creteil, France, ²Medical Oncology Department, Hopital Tenon, Paris, France, ³Centre of Early Clinical Trials in Cancer, Hôpital Européen Georges-Pompidou, Université Paris Cité, Paris, France, ⁴Radiation Oncology Department, Georges Pompidou European Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France, ⁵Medical Oncology Department, Hôpital Foch, Paris, France, ⁶Department of Radiation Oncology , Tenon University Hospital, Hôpitaux Universitaires Est Parisien, Sorbonne University Medical Faculty, Paris, France, ⁷Department of Medical Oncology, INSERM U938, Institut Universitaire de Cancérologie AP-HP Sorbonne Université, Paris, France, ⁸Department of Medical Oncology, The Henri Mondor University Hospital, Creteil, France, ⁹Oncologie-radiothérapie GHU Henri Mondor, Université Paris Est Créteil (UPEC), Inserm – IMRB U 955 (i-Biot), Creteil, France

Purpose/Objective(s): Trastuzumab Deruxtecan (T-DXd) is a new antibody drug conjugate (ADC) particularly recommended in the treatment of HER2 overexpressed (IHC 3+ or IHC 2+/ISH+) and HER2 low (IHC 2+/1+ and ISH-) metastatic breast cancer (MBC). Patients in metastatic setting may receive radiotherapy (RT) for palliative of ablative curative intent combined to T-DXd. TENDANCE study aimed to report the first data on toxicity and efficacy of this combined therapy. Materials/

Methods: This is the first multicenter retrospective study that include patients treated concurrently with T-DXd and RT for HER 2+ and HER2 low MBC. Between February 2021 and December 2023, 54 patients were treated with T-DXd and concurrent RT in five French centers. All data were collected from a web-questionnaire, centralized after medical records and validation of the protocol by the local ethical committee.
Results: The median age was 60 years [39.6-85.7] and 24.1% of patients were over 70 years of age. Patients were treated for either HER2+ (40.7%), HER2 low/HR+ (40.8%) and HER2 low/HR- (18.5%). In the HER2+ patients, T-DXd was administered as 2nd (18.2%) or 3rd (31.8%) or 4th (50%) line therapy. For HER2 low/HR+ patients, T-DXd was administered as salvage treatment between the 2nd and the 6^th line therapy in 9.1%, 22.7%, 18.2%, 27.3%, 22.7%, respectively. For HER2 low/HR- patients, T-DXd was administered as 2nd line (20%) or 3rd line (20%) or 4th line (60%) therapy. Among the 54 patients, 72.2% received RT for palliative indications and 27.8% for curative intent. 37% of patients had stereotactic radiation therapy (SBRT), 57.4% 3D-conformal radiotherapy (3d CRT) and 5.6% IMRT/VMAT. Indications consisted of palliative bone irradiation (46.3%), or intracranial SBRT (25.9%), brain irradiation (14.8%), extracranial SBRT (7.4%) and breast RT (5.6%). The median time between initiation of T-DXd and the first RT session was 48 days. The median time between the last dose of T-DXd and the first RT session was 10 days [1-21] while the median time between the last RT session and the next T-DXd administration was 11.0 days [3-25]. After a first median assessment of 3 months, 22.2% of patients had a complete response and 77.8% experienced either a partial response or stable disease. Only 13.0% of patients presented grade 1 or 2 toxicities during radiotherapy after a median follow-up of six months. No patient had > grade 3 toxicity whatever the treated volume or fractionation. SBRT patients had no grade > 3 toxicity. Additionally, there was no T-DXd therapy discontinuation related to RT.
Conclusion: To our knowledge, TENDANCE study is the first report evaluating the association of concurrent T-DXd and RT. These results suggest very limited and manageable grade 1-2 toxicity, with an optimal clinical benefit from a non-discontinued T-DXd-RT combination. Our results are encouraging for practice but require confirmation with longer follow-up and by furth prospective studies.