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. 2024 Nov 21;10(1):100.
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  1 , Mariella A Mestres-Villanueva  2 , Sreenija Yarlagadda  3 , Ajay Doniparthi  4 , David B Smith  5 , Justyn Y Nakashima  1 , John M Bryant  1 , Dekuang Zhao  1 , Rituraj Upadhyay  2 , Matthew N Mills  1 , Daniel E Oliver  1 , Hsiang-Hsuan Michael Yu  1 , Joshua D Palmer  2 , Nicole O Williams  6 , Reshma L Mahtani  7 , Manmeet S Ahluwalia  7 , Hatem H Soliman  8 , Hyo S Han  8 , Aixa E Soyano  8 , Youngchul Kim  9 , Rupesh Kotecha  3 , Sasha J Beyer  2 , Kamran A Ahmed  10
Affiliations

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

Vaseem M Khatri et al. NPJ Breast Cancer. .

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+.

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Conflict of interest statement

Competing interests: H.-H.M.Y. has received speaker’s honoraria from BrainLab and is on the advisory boards of Novocure and Abbvie. H.S. serves as a consultant for Astrazeneca, Celgene, Novartis, PUMA, and Eisai. H.S. is on advisory boards for Novartis, Eisai, PUMA, Eli Lilly, Astrazeneca. Speaker fees for Merck. H.S.H. declares that she has received research funding from Abbvie, Arvinas, Pfizer, Seagen, Zymeworks and Quantum leap healthcare collaborative and on advisory boards for Pfizer and Arvinas. K.A.A. has received research funding from Bristol-Myers Squibb, Eli Lilly, and Genentech. R.K. has received honoraria from Accuray Inc., Elekta AB, ViewRay Inc., Novocure Inc., Elsevier Inc., Brainlab, Kazia Therapeutics, Castle Biosciences, and Ion Beam Applications and institutional research funding from Medtronic Inc., Blue Earth Diagnostics Ltd., Novocure Inc., GT Medical Technologies, AstraZeneca, Exelixis, ViewRay Inc., Brainlab, Cantex Pharmaceuticals, Kazia Therapeutics, and Ion Beam Applications. R.M. is a consultant/advisor for Agendia, Amgen, Astra Zeneca, Daiichi, Eisai, Genentech, Gilead, Hologic, Lilly, Novartis, Pfizer, Puma, Sanofi, Sermonix, Stemline. M.A. has received consulting fees from Bayer, Kiyatec, Insightec, GSK, Xoft, Nuvation, SDP Oncology, Apollomics, Prelude, Janssen, Voyager Therapeutics, Viewray, Caris Lifesciences, Pyramid Biosciences, Varian Medical Systems, Cairn Therapeutics, AnheartTherapeutics, Theraguix, MenariniRicerche, Sumitomo Pharma Oncology, Autem therapeutics, GT Medical Technologies, Allovir, EquilliumBio., QV Bioelectronics, grants to the institution from Seattle Genetics, is on the scientific advisory board of Modifibiosciences, Bugworks, reports stock in Mimivax, Cytodyn, MedInnovate Advisors LLC, Trisalus Life Sciences, and is on the data safety monitoring committee for VBI Vaccines.

Figures

Fig. 1
Fig. 1. Rates of symptomatic radiation necrosis.
Cumulative incidence of symptomatic radiation necrosis (A) per lesion and (B) per patient.
Fig. 2
Fig. 2. Local control analysis in all treated lesions.
Kaplan–Meier curve for local control.
Fig. 3
Fig. 3. Distant intracranial control and systemic progression free survival analysis by HER2 status.
Kaplan–Meier curves for (A) distant intracranial control (B) systemic progression free survival by HER2 status.
See this image and copyright information in PMC

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