V. M. Khatri1, M. Mestres-Villanueva2, A. Doniparthi3, D. B. Smith4, J. Y. Nakashima1, D. Zhao5, J. M. Bryant5, M. N. Mills1, D. E. Oliver1, H. H. M. Yu1, H. S. Han6, H. Soliman6, H. K. Perlow7, R. Upadhyay8, J. D. Palmer9, S. Beyer9, and K. A. Ahmed10; 1H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, 2Ohio State University College of Medicine, Columbus, OH, 3University of South Florida Morsani College of Medicine, Tampa, FL, 4West Virginia University School of Medicine, Morgantown, WV, 5Moffitt Cancer Center, Tampa, FL, 6H. Lee Moffitt Cancer Center and Research Institute, Department of Breast Oncology, Tampa, FL, 7Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 8The James Ohio State, New Delhi, India, 9Department of Radiation Oncology, The James Cancer Center, Ohio State University Wexner Medical Center, Columbus, OH, 10Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Purpose/Objective(s): To report oncologic and safety outcomes of combined stereotactic radiosurgery (SRS) and the antibody drug conjugate (ADC) trastuzumab-deruxtecan (T-DXd) for the management of HER2+ breast cancer brain metastases (BM). Retrospective series have raised concerns over a potentially increased risk of radiation necrosis when combining ADCs and SRS. Materials/
Methods: Patients who received T-DXd at 2 institutions from 2021-2023 were identified. Patients were included if they received T-DXd and SRS for the management of active HER2+ BM, within 6 months before T-DXd initiation or after discontinuation. Patients with prior leptomeningeal disease (LMD) were excluded. HER2-low disease was defined as HER2 immunohistochemistry 1+ or 2+ without amplification on in-situ hybridization. The Kaplan-Meier (KM) method was used to estimate extracranial progression free survival (EC-PFS), overall survival (OS), local control (LC), and distant intracranial control (DIC). Adverse events and symptomatic radiation necrosis (RN) were collected and diagnosed after multidisciplinary discussion including available radiologic and clinical information, with the onset of new neurologic symptoms. Cox proportional hazards model was used to identify prognostic variables. Results: Between 2021 and 2023, 31 patients received T-DXd and SRS over 48 courses to 171 lesions. Median follow up from T-DXd initiation was 21.2 months (range 7.4-38.1). Median age at the time of T-DXd was 50 (range 30-77). Twenty (65%) patients were hormone receptor positive. Sixteen (52%) patients were HER2-low. Seven (23%) patients had neurologic symptoms at the start of T-DXd. One hundred and nineteen (70%) lesions were treated with SRS and 52 (30%) with fractionated (f)SRS. Ninety-two (54%) lesions received concurrent T-DXd and SRS. Median RT dose was 20 Gy (range 18-24) for lesions treated with SRS, and 24 Gy (range 15-35) in a median of 3 fractions (range 3-10) for fSRS. Five lesions were treated post-operatively. Median GTV size was 0.07 cc (range 0.01-33.04) and median PTV size was 0.31 cc (range 0.04-65.01). Median OS was 16 months (95% CI 8-NR), with a 12-month OS rate of 54%. HER2-low disease was associated with decreased OS (HR 3.3, 95% CI 1.0-11.4, p = 0.04). Median EC-PFS was 5.2 months (95% CI 3.0-8.7), and 12-month EC-PFS rate was 33% for HER2+ disease and 0% for HER2-low. HER2-low disease was associated with extracranial progression or death (HR 4.4, 95% CI 1.6-12.1, p = 0.004). Median DIC per treatment course was 5.7 months (95% CI 2.5-8.9) with a 12-month DIC rate of 20%. DIC at 12-months for HER2+ patients was 32% compared to 7% for HER2-low (p=0.1). The 12-month LC was 97%. RN was noted in 2 (1%) lesions. Four (13%) patients developed LMD. Conclusion: The combination of SRS and T-DXd was found to have excellent local control and did not appear to increase the risk of radiation necrosis. HER2-low patients were found to have poorer OS and EC-PFS. Prospective investigation is warranted.
