medwireNews: The antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) induces a high intracranial response rate among women with HER2-positive breast cancer and active brain metastases, TUXEDO-1 study findings indicate.
Speaking at the ESMO Breast Cancer Congress 2022 in Berlin, Germany, Rupert Bartsch from the Medical University of Vienna in Austria said that the data add “to the growing body of evidence that systemic therapy is feasible in patients with active brain metastasis.”
The single-arm, phase 2 study included 15 women (median age 69 years) with HER2-positive breast cancer and newly diagnosed, untreated brain metastases (40%) or brain metastases progressing after local therapy (60%). They were given T-DXd 5.4 mg/kg every 3 weeks until disease progression, unacceptable toxicity, or withdrawal for other reasons.
All participants had prior exposure to trastuzumab and pertuzumab and no indication for immediate local therapy, and 70% had previously received trastuzumab emtansine.
Bartsch reported that, during a median 11 months of follow-up, two patients died as a result of disease progression. Median progression-free survival was 14 months and median overall survival was not reached.
The intracranial response rate (RR) – the primary study endpoint – was 73.3% in the intention-to-treat population and was 78.6% in the per-protocol population, which excluded one patient initially assessed as having parenchymal brain metastasis who was later found to have dural metastasis only upon restaging.
All but one patient in the per-protocol population experienced clinical benefit (complete or partial response or stable disease for at least 6 months) and the extracranial RR was 62.5% in the eight patients with measurable extracranial disease at baseline.
Bartsch said that “no new safety signals were observed and as you would expect with trastuzumab deruxtecan, the main toxicity consisted of anemia, neutropenia, fatigue, and nausea.” The majority of adverse events (AEs) were grade 1 or 2 in severity, but four patients experienced a total of six serious AEs.
Among the AEs of special interest, one patient with diabetes experienced a grade 3 symptomatic drop of left ventricular ejection fraction and one patient experienced grade 2 interstitial lung disease that completely resolved after 6 weeks of corticosteroid treatment. No patients discontinued treatment due to toxicity and there were no treatment-related deaths.
The presenter also noted that quality of life measures, including for cognitive function, were maintained over the treatment period.
And he concluded that the study “supports further investigation of ADCs in the context of secondary CNS [central nervous system] malignancies.”
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