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. 2022 Sep 1;11(3):CNS90.
doi: 10.2217/cns-2022-0010. Epub 2022 Jun 8.

Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan

Nelson S Moss  1 , Umberto Tosi  1   2 , Bianca D Santomasso  3 , Kathryn Beal  4 , Shanu Modi  5
Affiliations

Multifocal and pathologically-confirmed brain metastasis complete response to trastuzumab deruxtecan

Nelson S Moss et al. CNS Oncol. .

Abstract

Antibody-drug conjugates have transformed the treatment of HER2+ breast and other cancers. Unfortunately, the CNS remains a sanctuary site for many such patients in part due to poor macromolecule penetration across the blood-brain tumor barrier. Trastuzumab deruxtecan (T-DXd), a high-payload antibody-drug conjugate, was recently found to improve progression-free survival in HER2+ breast cancer patients versus prior-generation trastuzumab emtansine, prompting us to evaluate CNS activity in a woman with brain-only metastatic disease. T-DXd achieved complete response despite heavy pretreatment. Three persistent, previously-irradiated lesions were biopsy-proven to represent treatment effect. Subsequent recurrence occurred upon treatment holiday; partial response was observed with rechallenge. This case suggests T-DXd is active in HER2+ breast cancer brain metastases and supports further prospective evaluation.

Keywords: brain neoplasm; breast neoplasms; metastasis; trastuzumab deruxtecan.

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Figures

Figure 1.
Figure 1.. Multifocal brain metastasis response to T-DXd.
Side-by-side comparison of post contrast, T1-weighted MRIs done before (left-sided panels) and 6 weeks after initiation of T-DXd. Each arrow indicates a metastasis that resolved after treatment initiation. TDXd: Trastuzumab deruxtecan.
Figure 2.
Figure 2.. Severe necrosis of two metastases.
(A) T1-weighted, post contrast MRI showing prominent size of a dominant left frontoparietal lesion. (B) Postoperative pathology showing necrotic and fibrinous material and, at upper right, dystrophic mineralization without evidence of active tumor (H&E staining). (C) T1-weighted, post contrast MRI showing a dominant, bilobed left frontal lesion with surrounding vasogenic edema responsible for the patient’s symptoms and treated via LITT. (D) Pathology of the targeted lesion showing tissue necrosis with few mononuclear cells (H&E). LITT: Laser-interstitial thermal therapy.
Figure 3.
Figure 3.. Multifocal brain metastasis response to T-DXd with rechallenge.
Post contrast T1-weighted MRI showing (A) progression of CNS disease in the setting of a T-DXd holiday and (B) improvement of most lesion upon T-DXd reinstatement (2 months after (A)). Each arrow indicates a metastasis that resolved after treatment initiation. TDXd: Trastuzumab deruxtecan.
See this image and copyright information in PMC

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