Trastuzumab deruxtecan (Enhertu)

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General information

Class/mechanism from the NCI Drug Dictionary: An antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (ERBB2; EGFR2; HER2) conjugated to a derivative of the camptothecin analog exatecan (DXd; DX-8951 derivative), a DNA topoisomerase 1 (topoisomerase I; Top1) inhibitor, with potential antineoplastic activity. Upon administration of anti-HER2 ADC conjugate DS-8201a, the antibody moiety targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, the DX-8951 derivative moiety binds to and inhibits Top1-DNA complexes, which results in an inhibition of DNA replication, cell cycle arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. In addition, DS-8201a induces antibody-dependent cell-mediated cytotoxicity (ADCC) and causes a bystander killing effect, thereby killing neighboring HER2-expressing tumor cells.
Route: IV

For conciseness and simplicity, 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]

Diseases for which it is used

History of changes in FDA indication

Breast cancer

  • 12/20/2019: Granted accelerated approval for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. (Based on DESTINY-Breast01)
  • 5/4/2022: Approved for adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy. (Converted to full approval; Based on DESTINY-Breast03)

Gastric cancer

Patient Drug Information

Also known as

  • Code name: DS-8201a
  • Generic name: fam-trastuzumab deruxtecan-nxki
  • Brand name: Enhertu