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Fam-trastuzumab Deruxtecan-nxki for Metastatic Breast Cancer With Brain Metastases

By: Julia Fiederlein
Posted: Wednesday, July 7, 2021

Based on the findings of the ongoing, two-part, multicenter, open-label, phase II DESTINY-Breast01 trial, fam-trastuzumab deruxtecan-nxki was approved for the treatment of adults with HER2-positive unresectable or metastatic breast cancer who received at least two prior anti–HER2-based regimens (the United States and Europe) or had prior chemotherapy and are refractory to or intolerant of standard treatments (Japan). The subgroup analysis of patients with a history of brain metastases, which was presented by Guy Heinrich Maria Jerusalem, MD, PhD, of Liège University, Belgium, and colleagues during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 526), highlighted the durable clinical activity of this HER2-directed antibody-drug conjugate.

The trial enrolled adults with HER2-positive unresectable or metastatic breast cancer who were previously treated with trastuzumab emtansine; a total of 24 patients with a history of brain metastases at baseline who received 5.4 mg/kg of trastuzumab deruxtecan every 3 weeks were included in the subgroup analysis. In this population, an MRI of the brain was taken every 6 weeks.

The objective response rate, the median duration of progression-free survival, and the median duration of response were 58.3%, 18.1 months, and 16.9 months, respectively, in the subgroup of patients with brain metastases. Similarly, in the overall population (n = 184), they were 60.9%, 16.4 months, and 14.8 months, respectively. The rates of disease progression seemed to be comparable between patients with and without brain metastases (33% vs. 25%); this finding suggested durable systemic disease control. The central nervous system response rate was 50% among the 14 patients with information available on the diameter of baseline brain metastases.

“The demonstrable response of brain metastases to treatment and durable clinical activity of trastuzumab deruxtecan in patients with a history of brain metastases at baseline are promising and warrant further investigation,” the investigators concluded.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.



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