Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases

Vaseem M Khatri; Mariella A Mestres-Villanueva; Sreenija Yarlagadda; Ajay Doniparthi; David B Smith; Justyn Y Nakashima; John M Bryant; Dekuang Zhao; Rituraj Upadhyay; Matthew N Mills; Daniel E Oliver; Hsiang-Hsuan Michael Yu; Joshua D Palmer; Nicole O Williams; Reshma L Mahtani; Manmeet S Ahluwalia; Hatem H Soliman; Hyo S Han; Aixa E Soyano; Youngchul Kim; Rupesh Kotecha; Sasha J Beyer; Kamran A Ahmed

doi:10.1038/s41523-024-00711-w

Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases

NPJ Breast Cancer. 2024 Nov 21;10(1):100. doi: 10.1038/s41523-024-00711-w.

Authors

Vaseem M Khatri¹, Mariella A Mestres-Villanueva², Sreenija Yarlagadda³, Ajay Doniparthi⁴, David B Smith⁵, Justyn Y Nakashima¹, John M Bryant¹, Dekuang Zhao¹, Rituraj Upadhyay², Matthew N Mills¹, Daniel E Oliver¹, Hsiang-Hsuan Michael Yu¹, Joshua D Palmer², Nicole O Williams⁶, Reshma L Mahtani⁷, Manmeet S Ahluwalia⁷, Hatem H Soliman⁸, Hyo S Han⁸, Aixa E Soyano⁸, Youngchul Kim⁹, Rupesh Kotecha³, Sasha J Beyer², Kamran A Ahmed¹⁰

Affiliations

¹ Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
² Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 43201, USA.
³ Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA.
⁴ University of South Florida Morsani College of Medicine, Tampa, FL, 33602, USA.
⁵ West Virginia University School of Medicine, Morgantown, WV, 26506, USA.
⁶ Department of Medical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 43201, USA.
⁷ Department of Medical Oncology; Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 33176, USA.
⁸ Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
⁹ Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA.
¹⁰ Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 33612, USA. [email protected].

Abstract

Trastuzumab-deruxtecan (T-DXd) has demonstrated intracranial efficacy; however, safety and efficacy data remains limited with stereotactic radiosurgery (SRS). A multi-institutional review was performed with HER2+ or HER2-low metastatic breast cancer treated with T-DXd and SRS for active brain metastases. We identified 215 lesions treated over 48 SRS courses in 34 patients. Median follow up from T-DXd initiation was 13.9 months. The cumulative incidence of symptomatic radiation necrosis at 24 months per lesion was 2.1% and per patient 11%. The 12-month LC was 97%. HER2-low was associated with worse distant intracranial control (DIC) (adjusted HR 2.5, 95% CI 1.1-5.6, p = 0.03) and worse systemic progression free survival (PFS) (HR 4.1, 95% CI 1.6-10.7, p = 0.004). Concurrent SRS and T-DXd has excellent local control, without an increased risk of radiation necrosis. HER2-low disease is associated with worse systemic PFS and DIC with T-DXd compared to HER2+.