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

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

Acknowledgments

The authors would like to thank MK Rosenblum for neuropathologic review.

Financial & competing interests disclosure

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. At the time of research execution and publication, all authors are affiliated with Memorial Sloan Kettering Cancer Center. The authors of this research deny any conflicts of interest regarding this study, and make the following disclosures: NS Moss: Consulting fees for advisory board participation: AstraZeneca; trial funding: GT Medical Technologies. BD Santomasso: Consulting fees for advisory board participation: Janssen, Legend, BMS, Incyte, In8bio. S Modi: Research funding: Genentech, Daiichi Sankyo, AstraZeneca, Seagen; Consultant/Advisory/Speaking honoraria: Genentech, Daiichi Sankyo, AstraZeneca, Seagen, Macrogenics, Novartis, Glaxo-Smith Kline, Zymeworks. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Informed consent disclosure

The authors state that they have obtained appropriate Institutional Review Board approval or have followed the principles outlined in the Declaration of Helsinki for all human investigations. In addition, informed consent has been obtained from the participants involved. This work is compliant with CARE guideline.

Additional information

Funding

This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. At the time of research execution and publication, all authors are affiliated with Memorial Sloan Kettering Cancer Center. The authors of this research deny any conflicts of interest regarding this study, and make the following disclosures: NS Moss: Consulting fees for advisory board participation: AstraZeneca; trial funding: GT Medical Technologies. BD Santomasso: Consulting fees for advisory board participation: Janssen, Legend, BMS, Incyte, In8bio. S Modi: Research funding: Genentech, Daiichi Sankyo, AstraZeneca, Seagen; Consultant/Advisory/Speaking honoraria: Genentech, Daiichi Sankyo, AstraZeneca, Seagen, Macrogenics, Novartis, Glaxo-Smith Kline, Zymeworks. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.