Trastuzumab-DM1: a clinical update of the novel antibody-drug conjugate for HER2-overexpressing breast cancer.
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Barginear MF, John V, Budman DR
Trastuzumab-DM1: a clinical update of the novel antibody-drug conjugate for HER2-overexpressing breast cancer.
Mol Med. 2013 Jan 22;18:1473-9. doi: 10.2119/molmed.2012.00302.
- PubMed ID
- 23196784 [ View in PubMed]
- Abstract
Trastuzumab is a monoclonal antibody targeted against the HER2 tyrosine kinase receptor. Although trastuzumab is a very active agent in HER2-overexpressing breast cancer, the majority of patients with metastatic HER2-overexpressing breast cancer who initially respond to trastuzumab develop resistance within 1 year of initiation of treatment and, in the adjuvant setting, progress despite trastuzumab-based therapy. The antibody-drug conjugate trastuzumab-DM1 (T-DM1) was designed to combine the biological activity of trastuzumab with the targeted delivery of a highly potent antimicrotubule agent, DM1 (N-methyl-N-[3-mercapto-1-oxopropyl]-l-alanine ester of maytansinol), a maytansine derivative, to HER2-overexpressing breast cancer cells. T-DM1 is the first antibody-drug conjugate with a nonreducible thioether linker in clinical trials. Phase I and II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are awaiting final results; the EMILIA trial is evaluating T-DM1 compared with lapatinib plus capecitabine, and early positive results have been reported. The MARIANNE trial is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Here, we summarize evidence from clinical studies and discuss the potential clinical implications of T-DM1.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Trastuzumab emtansine Receptor tyrosine-protein kinase erbB-2 Protein Humans YesAntibodyDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareTrastuzumab emtansineMethimazole The metabolism of Trastuzumab emtansine can be decreased when combined with Methimazole. Trastuzumab emtansineRitonavir The metabolism of Trastuzumab emtansine can be decreased when combined with Ritonavir. Trastuzumab emtansineKetoconazole The metabolism of Trastuzumab emtansine can be decreased when combined with Ketoconazole. Trastuzumab emtansineNefazodone The metabolism of Trastuzumab emtansine can be decreased when combined with Nefazodone. Trastuzumab emtansineItraconazole The metabolism of Trastuzumab emtansine can be decreased when combined with Itraconazole.