Difference between revisions of "Trastuzumab emtansine (Kadcyla)"
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m (PeterYang moved page Trastuzumab emtansine (T-DM1) to Ado-trastuzumab emtansine (Kadcyla): FDA approval) |
(FDA approval) |
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| − | Also known as TDM1. | + | Also known as TDM1, T-DM1, trastuzumab emtansine. |
==General information== | ==General information== | ||
| − | Class: Antibody | + | Class: Antibody-cytotoxic agent conjugate consisting of the HER2 humanized IgG1 kappa monoclonal antibody [[Trastuzumab (Herceptin)]] linked with a small molecule microtubule inhibitor and maytansine derivative, emtansine (DM1). The humanized monoclonal antibody binds to subdomain IV of the HER2 receptor, is subjected to receptor-mediated endocytosis, and lysosomal degradation leads to the intracellular release of DM1. DM1 binds to tubulin at the rhizoxin binding site, inhibits the assembly of microtubules, and leads to cell cycle arrest and cell death via apoptosis. Similar to [[Trastuzumab (Herceptin)]], ado-trastuzumab emtansine inhibits HER2 receptor signaling, facilitates antibody-dependent cell-mediated cytotoxicity (ADCC), and inhibits shedding of the HER2 extracellular domain in HER2-overexpressing human breast cancer cells.<ref name="insert">[http://www.gene.com/download/pdf/kadcyla_prescribing.pdf Ado-trastuzumab emtansine (Kadcyla) package insert]</ref><ref>[[Media:Adotrastuzumabemtansine.pdf|Ado-trastuzumab emtansine (Kadcyla) package insert (locally hosted backup)]]</ref><ref>[http://www.kadcyla.com/ Kadcyla manufacturer's website]</ref><ref>[http://www.immunogen.com/wt/page/trastuzumab_DM1 ImmunoGen product site]</ref><ref>http://www.immunogen.com/img/T-DM1%20+%20pertuzumab%20at%20SABCS.pdf A Phase Ib/II Trial of Trastuzumab-DM1 (T-DM1) with Pertuzumab for Patients with HER2-Positive, |
Locally Advanced or Metastatic Breast Cancer: Interim Efficacy and Safety Results</ref><ref>[http://ecancer.org/tv/pubdate/1087 Dr. Sara Hurvitz's 2011 European Society for Medical Oncology (ESMO) Presentation]</ref> | Locally Advanced or Metastatic Breast Cancer: Interim Efficacy and Safety Results</ref><ref>[http://ecancer.org/tv/pubdate/1087 Dr. Sara Hurvitz's 2011 European Society for Medical Oncology (ESMO) Presentation]</ref> | ||
<br>Route: IV | <br>Route: IV | ||
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For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information. | For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as [http://www.thomsonhc.com/home/dispatch Micromedex], [http://online.lexi.com/ Lexicomp], [http://www.utdol.com/online/content/search.do UpToDate (courtesy of Lexicomp)], or the prescribing information. | ||
| + | |||
| + | ==Diseases for which it is used== | ||
| + | *[[Breast cancer]] | ||
==Clinical trials== | ==Clinical trials== | ||
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==Patient drug information== | ==Patient drug information== | ||
| − | + | *Patient counseling information can be found on [http://www.gene.com/download/pdf/kadcyla_prescribing.pdf#page=22 page 22 of the Ado-trastuzumab emtansine (Kadcyla) package insert]<ref name="insert"></ref> | |
| + | |||
| + | ==History of changes in FDA indication== | ||
| + | *2/22/2013: [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm340704.htm FDA approved] for "patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination." | ||
==References== | ==References== | ||
<references/> | <references/> | ||
| + | |||
| + | [[Category:Drug index]] | ||
| + | [[Category:Chemotherapy]] | ||
| + | [[Category:Antibody medications]] | ||
| + | [[Category:Antibody-drug conjugates]] | ||
| + | [[Category:Anti-HER2 medications]] | ||
| + | [[Category:Microtubule inhibitors]] | ||
| + | [[Category:Breast cancer medications]] | ||
| + | [[Category:Drugs FDA approved in 2013]] | ||
Revision as of 00:10, 23 February 2013
Also known as TDM1, T-DM1, trastuzumab emtansine.
General information
Class: Antibody-cytotoxic agent conjugate consisting of the HER2 humanized IgG1 kappa monoclonal antibody Trastuzumab (Herceptin) linked with a small molecule microtubule inhibitor and maytansine derivative, emtansine (DM1). The humanized monoclonal antibody binds to subdomain IV of the HER2 receptor, is subjected to receptor-mediated endocytosis, and lysosomal degradation leads to the intracellular release of DM1. DM1 binds to tubulin at the rhizoxin binding site, inhibits the assembly of microtubules, and leads to cell cycle arrest and cell death via apoptosis. Similar to Trastuzumab (Herceptin), ado-trastuzumab emtansine inhibits HER2 receptor signaling, facilitates antibody-dependent cell-mediated cytotoxicity (ADCC), and inhibits shedding of the HER2 extracellular domain in HER2-overexpressing human breast cancer cells.[1][2][3][4][5][6]
Route: IV
Extravasation: no information
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.
Diseases for which it is used
Clinical trials
- EMILIA: A phase III, randomized, multicenter study of trastuzumab-DM1 (T-DM1) compared with lapatinib (L) plus capecitabine (X) in patients with HER2-positive locally advanced or metastatic breast cancer (MBC) and previously treated with a trastuzumab-based regimen.[7][8]
- MARIANNE: A phase III, randomized study of trastuzumab-DM1 (T-DM1) with or without pertuzumab (P) compared with trastuzumab (H) plus taxane for first-line treatment of HER2-positive, progressive, or recurrent locally advanced or metastatic breast cancer (MBC).[9][10]
Patient drug information
- Patient counseling information can be found on page 22 of the Ado-trastuzumab emtansine (Kadcyla) package insert[1]
History of changes in FDA indication
- 2/22/2013: FDA approved for "patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination."
References
- ↑ 1.0 1.1 Ado-trastuzumab emtansine (Kadcyla) package insert
- ↑ Ado-trastuzumab emtansine (Kadcyla) package insert (locally hosted backup)
- ↑ Kadcyla manufacturer's website
- ↑ ImmunoGen product site
- ↑ http://www.immunogen.com/img/T-DM1%20+%20pertuzumab%20at%20SABCS.pdf A Phase Ib/II Trial of Trastuzumab-DM1 (T-DM1) with Pertuzumab for Patients with HER2-Positive, Locally Advanced or Metastatic Breast Cancer: Interim Efficacy and Safety Results
- ↑ Dr. Sara Hurvitz's 2011 European Society for Medical Oncology (ESMO) Presentation
- ↑ S. Verma, V. Dieras, L. Gianni, D. Miles, M. Welslau, M. D. Pegram, J. Baselga, E. Guardino, L. Fang, C. M. Linehan, K. L. Blackwell. EMILIA: A phase III, randomized, multicenter study of trastuzumab-DM1 (T-DM1) compared with lapatinib (L) plus capecitabine (X) in patients with HER2-positive locally advanced or metastatic breast cancer (MBC) and previously treated with a trastuzumab-based regimen. 2011 ASCO Annual Meeting abstract TPS116.
- ↑ EMILIA at ClinicalTrials.gov
- ↑ P. A. Ellis, C. H. Barrios, Y. Im, M. Patre, F. Branle, E. A. Perez. MARIANNE: A phase III, randomized study of trastuzumab-DM1 (T-DM1) with or without pertuzumab (P) compared with trastuzumab (H) plus taxane for first-line treatment of HER2-positive, progressive, or recurrent locally advanced or metastatic breast cancer (MBC). 2011 ASCO Annual Meeting abstract TPS102.
- ↑ MARIANNE at ClinicialTrials.gov