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May 2023 - Rupert Bartsch


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Assoc.-Prof. PD Dr. Rupert Bartsch


Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADCs) with high extracranial activity in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). In this breast cancer subtype, brain metastases (BM) are a common and devastating complication. While intracranial activity of small-molecule tyrosine kinase inhibitors is well established, the potential role of larger molecules such as ADCs remains ill-defined. The single-centre, single-arm, phase 2 trial TUXEDO-1 trial therefore enrolled patients with HER2-positive mBC and active (i.e., newly diagnosed or progressive) BM; intracranial response rate was defined as the primary study endpoint. In the intention-to-treat population, best intracranial response rate was 73.3% (95% confidential interval 48.1-89.1%), thus suggesting comparable extra- and intracranial activity. T-DXd should therefore be considered as a treatment option in the setting of HER2-positive breast cancer BM.

Selected Literature

  1. Bartsch R, Berghoff AS, Furtner J, Marhold M, Bergen ES, Roider-Schur S, Starzer AM, Forstner H, Rottenmanner B, Dieckmann K, Bago-Horvath Z, Haslacher H, Widhalm G, Ilhan-Mutlu A, Minichsdorfer C, Fuereder T, Szekeres T, Oehler L, Gruenberger B, Singer CF, Weltermann A, Puhr R, Preusser M. Trastuzumab deruxtecan in HER2-positive breast cancer with brain metastases: a single-arm, phase 2 trial. Nature Med 2022;28:1840-1847.

  2. Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody–drug conjugates for cancer therapy. Nature Reviews Clinical Oncology 2021;18: 327–344.

  3. Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, Chiu JWY, Xu B, Hamilton E, Madhusudan S, Iwata H, Altintas S, Henning JW, Curigliano G, Perez-Garcia JM, Kim SB, Petry V, Huang CS, Li W, Frenel JS, Antolin S, Yeo W, Bianchini G, Loi S, Tsurutani J, Egorov A, Liu Y, Cathcart J, Ashfaque S, Cortés J. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet 2023;401:105-117.

  4. Krop I, Park YH, Kim SB, Borges G, Aksoy S, Gregori JG, Roylance R, Lim E, Yerushalmi R, Zagouri F, Duhoux FP, Fehm T, Takano T, Egorov A, Wu I, Cathcart J, Chu C, André F. Trastuzumab deruxtecan vs physician’s choice in patients with HER2+ unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine: Primary results of the randomized phase 3 study DESTINY‑Breast02. Abst. GS2-01; presented at the 2022 San Antonio Breast Cancer Symposium, Dec. 6th-10th, 2022; San Antonio, TX, USA.

  5. Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med 2020;382:597-609.

Assoc.-Prof. PD Dr. Rupert Bartsch

Medizinische Universität Wien
Universitätsklinik für Innere Medizin I
Klinische Abteilung für Onkologie
Währinger Gürtel 18-20
1090 Wien

T: +43 (0)1 40400-44450