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Trastuzumab Emtansine: A Review of Its Use in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab-Based Therapy

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Abstract

Trastuzumab emtansine (Kadcyla™) is an antibody-drug conjugate consisting of the humanized anti-human epidermal growth factor receptor (HER) 2 antibody trastuzumab covalently linked to the highly potent microtubule inhibitory drug DM1 (a cytotoxic derivative of maytansine) via a stable thioether linker. Intravenous trastuzumab emtansine was recently approved for use in patients with HER2-positive, unresectable, locally advanced (in the EU) or metastatic (in the USA and EU) breast cancer who had previously received trastuzumab and a taxane (separately or in combination), making it the first antibody-drug conjugate approved in this indication. This article reviews the efficacy and tolerability of trastuzumab emtansine in these patients and summarizes its pharmacology. In the well-designed EMILIA study, trastuzumab emtansine significantly prolonged progression-free survival and overall survival, relative to treatment with lapatinib plus capecitabine, in patients with HER2-positive, unresectable, locally advanced or metastatic breast cancer who were previously treated with trastuzumab and a taxane. Trastuzumab emtansine was generally well tolerated in this study, with <6 % of patients discontinuing treatment because of adverse events. Based on its efficacy and favourable tolerability, the US National Comprehensive Cancer Network guidelines recommend trastuzumab emtansine as the preferred option in patients with HER2-positive metastatic breast cancer who have received previous trastuzumab-based therapy.

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Disclosure

The preparation of this review was not supported by any external funding. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author on the basis of scientific and editorial merit.

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    Sohita Dhillon

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Correspondence to Sohita Dhillon.

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The manuscript was reviewed by: A.U. Buzdar, Department of Breast Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA; S. Hurvitz, Department of Medicine, Division of Hematology-Oncology University of California-Los Angeles, Los Angeles, CA, USA; K.I. Pritchard, Department of Medicine, Division of Medical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada

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Dhillon, S. Trastuzumab Emtansine: A Review of Its Use in Patients with HER2-Positive Advanced Breast Cancer Previously Treated with Trastuzumab-Based Therapy. Drugs 74, 675–686 (2014). https://doi.org/10.1007/s40265-014-0201-0

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