Assoc.-Prof. PD Dr. Rupert Bartsch
MedUni Wien RESEARCHER OF THE MONTH May 2023
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
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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.
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Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody–drug conjugates for cancer therapy. Nature Reviews Clinical Oncology 2021;18: 327–344.
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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.
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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.