TUXEDO-1: Efficacy of T-DXd for Patients With HER2-Positive Breast Cancer and Active Brain Metastases

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In the single-center phase II TUXEDO-1 trial of patients with advanced HER2-positive breast cancer, fam-trastuzumab-deruxtecan-nxki (T-DXd) showed efficacy in patients with active brain metastases, yielding intracranial responses in 73.3% of the population and a median progression-free survival of 14 months, according to findings presented by Bartsch et al at the ESMO Breast Cancer Congress 2022 (Abstract 165MO).

“The study reached its primary endpoint, with comparable intracranial and extracranial response rates observed, and suggested there is prolonged disease control by systemic treatment with T-DXd. Importantly, quality-of-life neurocognitive functioning was maintained over the entire treatment period,” said presenting author Rupert Bartsch, MD, of the Medical University of Vienna.


TUXEDO-1 included 15 patients with HER2-positive metastatic breast cancer and brain metastases that were either newly diagnosed or had developed upon disease progression after local therapy. The brain metastases were untreated in 40% of patients, and, for 60%, had progressed after local therapy. Neurologic symptoms were present at baseline for 40% of patients. All patients were previously exposed to an anti-HER2–directed therapy, which for 60% included ado-trastuzumab emtansine (T-DM1). Patients received treatment with T-DXd at 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity.


  • T-DXd showed strong intracranial activity in patients with metastatic HER2-positive breast cancer and active brain metastases in the phase II TUXEDO-1 trial.
  • The intracranial response rate was 73.3%, and median progression-free survival was 14 months.

The primary endpoint, objective response, was seen in 73.3% of the intent-to-treat population of 15 patients and 78.6% of the per-protocol population of 14 patients.  The clinical benefit rate (≥ 6 months) was 86.7% and 92.9%, respectively.

“Nearly all patients benefited to some degree from systemic treatment,” noted Dr. Bartsch.

In eight patients with measurable extracranial disease at baseline, the response rate was 62.5%. After a median follow-up of 11 months, the median progression-free survival was 14 months and the median overall survival was not reached. 

No new safety signals were observed. As for adverse events of special interest, one patient with preexisting diabetes experienced a grade 3 left-ventricular ejection fraction decrease and one patient developed grade 2 interstitial lung disease that completely resolved after 6 weeks of corticosteroid treatment. One patient died of grade 5 urosepsis unrelated to treatment.

After decreasing upon initiation of treatment, patients maintained global health status and physical, emotional, and cognitive function.

“Importantly, in a trial conducted in patients with active brain metastases, cognitive functioning was maintained over the entire treatment period,” Dr. Bartsch said.

“TUXEDO-1, therefore, adds to the growing body of evidence that systemic treatment is feasible in patients with active brain metastases, and more generally supports further investigation of antibody-drug conjugates in the context of secondary central nervous system malignancies,” he said.

Disclosure: For full disclosures of the study authors, visit

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