Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial
Rupert Bartsch,Anna S. Berghoff,Julia Furtner,Maximilian Marhold,Elisabeth Bergen,Sophie Roider-Schur,Angelika M. Starzer,H. Forstner,B. Rottenmanner,Karin Dieckmann,Zsuzsanna Bago-Horvath,Helmuth Haslacher,Georg Widhalm,Aysegül Ilhan-Mutlu,Christoph Minichsdorfer,Thorsten Fuereder,Thomas Szekeres,Leopold Oehler,Birgit Gruenberger,Christian F. Singer,Ansgar Weltermann,Rainer Puhr,Matthias Preusser +22 more
TLDR
The TUXEDO-1 trial as discussed by the authors showed that trastuzumab deruxtecan showed a high intracranial response rate in patients with active brain metastases from HER2-positive breast cancer and should be considered as a treatment option in this setting.Abstract:
Abstract Trastuzumab deruxtecan is an antibody–drug conjugate with high extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. We conducted the prospective, open-label, single-arm, phase 2 TUXEDO-1 trial. We enrolled patients aged ≥18 years with HER2-positive breast cancer and newly diagnosed untreated brain metastases or brain metastases progressing after previous local therapy, previous exposure to trastuzumab and pertuzumab and no indication for immediate local therapy. Patients received trastuzumab deruxtecan intravenously at the standard dose of 5.4 mg per kg bodyweight once every 3 weeks. The primary endpoint was intracranial response rate measured according to the response assessment in neuro-oncology brain metastases criteria. A Simon two-stage design was used to compare a null hypothesis of <26% response rate against an alternative of 61%. Fifteen patients were enrolled in the intention-to-treat population of patients who received at least one dose of study drug. Two patients (13.3%) had a complete intracranial response, nine (60%) had a partial intracranial response and three (20%) had stable disease as the best intracranial response, with a best overall intracranial response rate of 73.3% (95% confidential interval 48.1–89.1%), thus meeting the predefined primary outcome. No new safety signals were observed and global quality-of-life and cognitive functioning were maintained over the treatment duration. In the TUXEDO-1 trial (NCT04752059, EudraCT 2020-000981-41), trastuzumab deruxtecan showed a high intracranial response rate in patients with active brain metastases from HER2-positive breast cancer and should be considered as a treatment option in this setting. read more
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Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases
Sheheryar Kabraji,Jing Ni,Sarah Sammons,Tianyu Li,Amanda E.D. Van Swearingen,Yanzhi Wang,Alyssa Pereslete,Liangge Hsu,Pamela J. DiPiro,Christopher D. Lascola,Heather K Moore,Melissa E. Hughes,Akshara Singareeka Raghavendra,Maria D. Gule-Monroe,Rashmi Krishna Murthy,Eric P. Winer,Carey K. Anders,Jean J. Zhao,Nan Lin +18 more
TL;DR: T-DXd demonstrates evidence of CNS activity in Her2-positive and HER2-low PDX models of BCBM and preliminary evidence of clinical efficacy in a multi-institution case series of patients with BCBM.
Journal ArticleDOI
Preclinical and Clinical Efficacy of Trastuzumab Deruxtecan in Breast Cancer Brain Metastases
TL;DR: Soffietti et al. as mentioned in this paper studied how T-DXd affects growth and overall survival in orthotopic patient-derived xenografts (PDX) of HER2-positive and HER2low breast cancer brain metastases (BCBM).
Journal ArticleDOI
Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis
TL;DR: In this article , trastuzumab deruxtecan (T-DXd; DS-8201) was evaluated in patients with heavily pretreated HER2-positive metastatic breast cancer (mBC).
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Resistance to antibody‐drug conjugates in breast cancer: mechanisms and solutions
TL;DR: In this paper , the mechanisms of ADC resistance are summarized into four categories: antibody mediated resistance, impaired drug trafficking, disrupted lysosomal function, and payload-related resistance.
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Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends
TL;DR: The authors in this paper reviewed the new strategies that are in development for the treatment of metastatic breast cancer patients, the mechanisms of action and toxicities, and highlighted the future perspectives of treatment in this setting.
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TL;DR: In heavily pretreated patients with HER2-positive metastatic breast cancer, including those with brain metastases, adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo.
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