Overview
11 DESCRIPTION Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody and topoisomerase inhibitor conjugate. Fam-trastuzumab deruxtecan-nxki is an antibody-drug conjugate (ADC) composed of three components: 1) a humanized anti-HER2 IgG1 monoclonal antibody (mAb), covalently linked to 2) a topoisomerase I inhibitor, via 3) a tetrapeptide-based cleavable linker.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker. Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death. 12.2 Pharmacodynamics Exposure-Response Relationships Exposure-response relationship for efficacy has not been fully characterized. Higher systemic exposure to fam-trastuzumab deruxtecan-nxki was associated with a higher incidence rate of any grade ILD.
Indications
- 1 INDICATIONS AND USAGE ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for: HER2-Positive Early Breast Cancer as neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP). ( 1.1 ) as adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment. ( 1.
Common Doses
- 5.4 mg
- 840 mg
- 420 mg
- 6.4 mg
Dosage
2 DOSAGE AND ADMINISTRATION Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine. ( 2.2 , 2.4 ) For intravenous infusion only . Do not administer as an intravenous push or bolus. DO NOT use Sodium Chloride Injection, USP. ( 2.4 ) Premedicate for prevention of chemotherapy-induced nausea and vomiting. ( 2.2 ) HER2-Positive Early Breast Cancer Neoadjuvant: ENHERTU 5.4 mg/kg every 3 weeks for 4 cycles, followed by THP regimen for 4 cycles. ( 2.2 , 2.3 ) Post Neoadjuvant: ENHERTU 5.4 mg/kg every 3 weeks for 14 cycles unless disease recurrence or unacceptable toxicity.
Black Box Warning
WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial Lung Disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and the need to immediately report symptoms [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ] .
Contraindications
- 4 CONTRAINDICATIONS None . None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.1) ] Neutropenia [see Warnings and Precautions (5.2) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with: HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and HER2-Positive (including IHC 3+) Solid Tumors are decreased white blood cell count, nausea, decreased hemoglobin,...
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.