Global InformationTrastuzumab emtansine information
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| Monoclonal antibody | |
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| Type | Whole antibody |
| Source | Humanized (from mouse) |
| Clinical data | |
| Trade names | Kadcyla |
| Other names | ado-trastuzumab emtansine, trastuzumab-DM1, T-DM1 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a613031 |
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| Routes of administration | Intravenous infusion |
| Drug class | Antineoplastic agent |
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| Pharmacokinetic data | |
| Bioavailability | N/A |
| Protein binding | 93% (in vitro) |
| Metabolism | Liver (CYP3A4/3A5-mediated) |
| Elimination half-life | 4 days |
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| Chemical and physical data | |
| Formula | C6448H9948N1720O2012S44·(C47H62ClN4O13S)n[citation needed] |
| Molar mass | 148.5 kg/mol[citation needed] |
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Trastuzumab emtansine,[7][8] sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1.[9][10][11][12] Trastuzumab alone stops growth of cancer cells by binding to the HER2 receptor, whereas trastuzumab emtansine undergoes receptor-mediated internalization into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind tubulin to cause mitotic arrest and cell death.[13] Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 specifically to tumor cells.[14] The conjugate is abbreviated T-DM1.
In the EMILIA clinical trial[15] of women with advanced HER2 positive breast cancer who were already resistant to trastuzumab alone, it improved median overall survival by 5.8 months (30.9 months vs. 25.1 months) compared to the combination of lapatinib and capecitabine.[14] Based on that trial, the U.S. Food and Drug Administration (FDA) approved marketing on 22 February 2013.[16][17][18]
Trastuzumab emtansine was developed by Genentech, and is manufactured by Lonza.[19]
- ^ Use During Pregnancy and Breastfeeding
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
- ^ https://www.guildlink.com.au/gc/ws/ro/pi.cfm?product=ropkadcy20714 [bare URL]
- ^ Cite error: The named reference
Kadcyla SmPCwas invoked but never defined (see the help page). - ^ Cite error: The named reference
Kadcyla FDA labelwas invoked but never defined (see the help page). - ^ Cite error: The named reference
Kadcyla EPARwas invoked but never defined (see the help page). - ^ Niculescu-Duvaz I (June 2010). "Trastuzumab emtansine, an antibody-drug conjugate for the treatment of HER2+ metastatic breast cancer". Curr. Opin. Mol. Ther. 12 (3): 350–60. PMID 20521224.
- ^ USAN Council (2009). "Statement On A Nonproprietary Name Adopted By The Usan Council: Trastuzumab Emtansine" (PDF). American Medical Association. Archived from the original (PDF) on 28 September 2012. Retrieved 22 February 2013.
- ^ LoRusso PM, Weiss D, Guardino E, Girish S, Sliwkowski MX (October 2011). "Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer". Clin. Cancer Res. 17 (20): 6437–47. doi:10.1158/1078-0432.CCR-11-0762. PMID 22003071.
- ^ Poon, Kirsten Achilles (6 May 2010). Safety Assessment of Antibody Drug Conjugates (PDF). Drug Development: From Small Molecules to Biologics. NorCal Society of Toxicology 2010 Spring Meeting. Archived from the original (PDF) on 13 April 2014. Retrieved 23 February 2013.
- ^ "Trastuzumab emtansine". National Cancer Institute (NCI). Retrieved 23 February 2013.
- ^ "FDA denies accelerated approval of Genentech's trastuzumab-DM1 (T-DM1) BLA for metastatic breast cancer" (Press release). Genentech. 27 August 2010. Retrieved 23 February 2013.
- ^ Teicher BA, Doroshow JH (November 2012). "The promise of antibody-drug conjugates". N. Engl. J. Med. 367 (19): 1847–8. doi:10.1056/NEJMe1211736. PMID 23134386.
- ^ a b Cite error: The named reference
NEJM-Vermawas invoked but never defined (see the help page). - ^ Cite error: The named reference
NCT00829166was invoked but never defined (see the help page). - ^ "New data from Phase III EMILIA study showed Roche's trastuzumab emtansine (T-DM1) significantly improved survival of people with HER2-positive metastatic breast cancer" (Press release). Hoffmann-La Roche. 27 August 2012. Archived from the original on 4 November 2021. Retrieved 23 February 2013.
- ^ Pollack A (22 February 2013). "F.D.A. Approves a New Drug for Advanced Breast Cancer". The New York Times. Retrieved 22 February 2013.
- ^ "FDA approves new treatment for late-stage breast cancer" (Press release). U.S. Food and Drug Administration (FDA). 22 February 2013. Archived from the original on 12 January 2017. Retrieved 22 February 2013.
This article incorporates text from this source, which is in the public domain.
- ^ Franklin J (24 July 2014). "Lonza profit boosted by drug production outsourcing". Reuters. Retrieved 28 July 2014.
