
==== Front
Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.085
vdae090.085
Final Category: Novel Targets in CNS Metastases (Non-Immunologic)
AcademicSubjects/MED00300
AcademicSubjects/MED00310
NVTG-11 EFFICACY OF TRASTUZUMAB DERUXTECAN IN HER2-POSITIVE AND HER2-LOW BREAST CANCER WITH ACTIVE BRAIN METASTASES
Burnside Georgiana Stanford University School of Medicine, Stanford, USA

Gu Bo Stanford University School of Medicine, Stanford, USA

Carlson-Clarke Brandon Stanford University School of Medicine, Stanford, USA

Lalwani Kriti Stanford University School of Medicine, Stanford, USA

Hayden-Gephart Melanie Stanford University School of Medicine, Stanford, USA

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i26i26
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

Trastuzumab deruxtecan (T-DXd) has demonstrated strong CNS penetrance for HER2+ breast cancer with brain involvement, but further evidence is needed to support the use of T-DXd in HER2-low patients. This institutional retrospective review investigates the efficacy of T-DXd between HER2+ and HER2-low breast cancers with active brain metastases (BM). Using the Stanford Research Repository from 2020-2023, we identified 36 patients with breast cancer and active BM treated with T-DXd. Out of the 36, 7 had HER2+ breast cancer and 29 had HER2-low breast cancer. Of the 7 HER2+ patients, 6 are still living with 5 still continuing on treatment while median survival of the 29 HER2-low patients was 18 months (95%LCL 7 with indeterminate UCL based on available data) with 12 still living and 2 continuing on treatment. Using RANO-BM criteria we measured intracranial objective response rate (ORR-IC) on MRI for those with available target lesion measurements at initiation and end of treatment (EOT) windows (n=33). Of the HER2+ patients (n=7), 1/7 (14%) showed complete response, 2/7 (29%) had partial response, 3/7 (43%) had stable disease, and 1/7 (14%) had progressive disease with a notable 73.7% reduction in size of target lesions but numerous new enhancing lesions at EOT. In contrast, of the HER2-low cohort (n=26), 6/26 (23%) demonstrated partial response, 8/26 (31%) had stable disease, and 12/26 (46%) had progressive disease. Of the 12 HER2-low patients with progressive disease, 2/12 had >30% reduction in size of target lesions but numerous new lesions at EOT. Despite some intracranial responses in HER2-low patients, their median survival and high progression rates indicate limited benefits, highlighting the need for more robust prospective studies to further investigate T-DXd’s efficacy in this subgroup.
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pmc
