Difference between revisions of "Trastuzumab emtansine (Kadcyla)"

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==General information==
 
==General information==
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Class/mechanism: 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>[[File: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/our-adc-technology/kadcyla 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,
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Class/mechanism: 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>[[:File: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/our-adc-technology/kadcyla 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

Revision as of 04:13, 20 September 2021

General information

Class/mechanism: 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: irritant

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, Medscape,UpToDate (courtesy of Lexicomp), or the prescribing information.[1]

Resistance mechanisms

  • Hunter FW, Barker HR, Lipert B, Rothé F, Gebhart G, Piccart-Gebhart MJ, Sotiriou C, Jamieson SMF. Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer. Br J Cancer. 2019 Dec 16. Epub ahead of print. link to original article PubMed

Diseases for which it is used

Patient drug information

History of changes in FDA indication

  • 2/22/2013: Initial approval for patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. (Based on EMILIA)
  • 5/3/2019: Approval expanded for the adjuvant treatment of patients with HER2-positive early breast cancer (EBC) who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. (Indication extended to the adjuvant setting; based on KATHERINE)

Also known as

  • Code name: PRO132365
  • Generic names: TDM1, T-DM1, trastuzumab emtansine
  • Brand name: Kadcyla

References

  1. ↑ 1.0 1.1 1.2 Ado-trastuzumab emtansine (Kadcyla) package insert
  2. ↑ Ado-trastuzumab emtansine (Kadcyla) package insert (locally hosted backup)
  3. ↑ Kadcyla manufacturer's website
  4. ↑ ImmunoGen product site
  5. ↑ 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
  6. ↑ Dr. Sara Hurvitz's 2011 European Society for Medical Oncology (ESMO) Presentation
  7. ↑ Ado-trastuzumab emtansine (Kadcyla) patient drug information (Chemocare)
  8. ↑ Ado-trastuzumab emtansine (Kadcyla) patient drug information (UpToDate)
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