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

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 KimRupesh Kotecha, Sasha J Beyer, Kamran A Ahmed

Miami Cancer Institute

Research output: Contribution to journal › Article › peer-review

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+.

Original language	English
Pages (from-to)	100
Journal	NPJ breast cancer
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41523-024-00711-w
State	Published - Nov 21 2024

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Khatri, V. M., Mestres-Villanueva, M. A., Yarlagadda, S., Doniparthi, A., Smith, D. B., Nakashima, J. Y., Bryant, J. M., Zhao, D., Upadhyay, R., Mills, M. N., Oliver, D. E., Yu, H.-H. M., Palmer, J. D., Williams, N. O., Mahtani, R. L., Ahluwalia, M. S., Soliman, H. H., Han, H. S., Soyano, A. E., ... Ahmed, K. A. (2024). Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases. NPJ breast cancer, 10(1), 100. https://doi.org/10.1038/s41523-024-00711-w

Khatri, VM, Mestres-Villanueva, MA, Yarlagadda, S, Doniparthi, A, Smith, DB, Nakashima, JY, Bryant, JM, Zhao, D, Upadhyay, R, Mills, MN, Oliver, DE, Yu, H-HM, Palmer, JD, Williams, NO, Mahtani, RL , Ahluwalia, MS, Soliman, HH, Han, HS, Soyano, AE, Kim, Y, Kotecha, R, Beyer, SJ & Ahmed, KA 2024, 'Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases', NPJ breast cancer, vol. 10, no. 1, pp. 100. https://doi.org/10.1038/s41523-024-00711-w

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

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+.",

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

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AU - Khatri, Vaseem M

AU - Mestres-Villanueva, Mariella A

AU - Yarlagadda, Sreenija

AU - Doniparthi, Ajay

AU - Smith, David B

AU - Nakashima, Justyn Y

AU - Bryant, John M

AU - Zhao, Dekuang

AU - Upadhyay, Rituraj

AU - Mills, Matthew N

AU - Oliver, Daniel E

AU - Yu, Hsiang-Hsuan Michael

AU - Palmer, Joshua D

AU - Williams, Nicole O

AU - Mahtani, Reshma L

AU - Ahluwalia, Manmeet S

AU - Soliman, Hatem H

AU - Han, Hyo S

AU - Soyano, Aixa E

AU - Kim, Youngchul

AU - Kotecha, Rupesh

AU - Beyer, Sasha J

AU - Ahmed, Kamran A

PY - 2024/11/21

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N2 - 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+.

AB - 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+.

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DO - 10.1038/s41523-024-00711-w

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