Trastuzumab deruxtecan
Indications
Trastuzumab deruxtecan is used for:
Breast Cancer
Adult Dose
Breast Cancer
Indicated for unresectable or metastatic HER2-positive breast cancer in adults who have received ?2 prior anti-HER2-based regimens in the metastatic setting
Do not substitute for or with trastuzumab or ado-trastuzumab emtansine
5.4 mg/kg IV q3Weeks (21-day cycle) until disease progression or unacceptable toxicity
Hepatic impairment
Mild (total bilirubin ?ULN and any AST >ULN or total bilirubin >1-1.5x ULN and any AST): No dose adjustment
Moderate (total bilirubin >1.5-3x ULN and any AST): No dose adjustment; due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd
Severe (total bilirubin >3 to 10x ULN and any AST): No data are available
Child Dose
Renal Dose
Renal impairment
Mild or moderate (CrCl 30 to <90 mL/min): No dose adjustment necessary
Severe (CrCl <30 mL/min): No data are available
Administration
Contra Indications
Precautions
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur
Severe neutropenia, including febrile neutropenia, can occur
Febrile neutropenia was reported; monitor complete blood cell counts before initiating treatment and before each dose, and as clinically indicated
Left ventricular ejection fraction (LVEF) decrease has been observed; may be at increased risk of developing left ventricular dysfunction
Based on its mechanism of action, may cause fetal harm when administered to a pregnant woman
Pregnancy-Lactation
Pregnancy
Based on its mechanism of action, fetal harm may occur when administered to pregnant women
No data are available on use in pregnant women
Monitor women who received trastuzumab deruxtecan during pregnancy or within 7 months prior to conception for oligohydramnios; if oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care
Advise patients of potential fetal risks
Clinical considerations
Monitor women who received treatment during pregnancy or within 7 months prior to conception for oligohydramnios
If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care
Contraception
Females of reproductive potential: Use effective contraception during treatment and for at least 7 months following the last dose
Males with female partners of reproductive potential: Use effective contraception during treatment and for at least 4 months following the last dose
Infertility
Based on findings in animal toxicity studies, may impair male reproductive function and fertility
Lactation
There is no data regarding the presence of fam-trastuzumab deruxtecan-nxki in human milk, the effects on the breastfed child, or the effects on milk production
Advise women not to breastfeed during treatment and for 7 months after the last dose
Interactions
Trastuzumab deruxtecan is a substrate of OATP1B1, OATP1B3, MATE2-K, P-gp, CYP3A4, MRP1 and BCRP; in vitro studies did not show evidence of meaningful clinical impact
Adverse Effects
Side effects of Trastuzumab deruxtecan :
>10%
WBC decreased (70%)
Hgb decreased (70%)
Neutrophil count decreased (62%)
Fatigue (59%)
Alopecia (46%)
AST increased (14-41%)
ALT increased (10-38%)
Platelet count decreased (37%)
Decreased appetite (32%)
Anemia (31%)
Neutropenia (28%)
Hypokalemia (26%)
Leukopenia (22%)
Thrombocytopenia (20%)
Headache (19%)
Neutropenia (16%)
Upper respiratory tract infection (15%)
Dye eye (11%)
1-10%
Rash (10%)
Dizziness (10%)
Grade (3 or 4)
Anemia (7%)
WBC decreased (7%)
Hgb decreased (7%)
Fatigue (6%)
Leukopenia (6%)
Hypokalemia (3-3.4%)
Thrombocytopenia (3.4%)
Interstitial lung disease (2.6%)
Infusion-related reactions (2.6%)
Febrile neutropenia (1.7%)
Decreased appetite (1.3%)
Dyspnea (1.3%)
<1%
Grade (3 or 4)
AST increased (0.9%)
ALT increased (0.4-0.9%)
Dry eye (0.4%)
Alopecia (0.4%)
Mechanism of Action
HER2-targeted antibody-drug conjugate (ADC) which contains the humanized anti-HER2 IgG1, trastuzumab, covalently linked to the topoisomerase I inhibitor, deruxtecan
HER2 is a tyrosine kinase receptor growth-promoting protein found on the surface of some cancer cells that is associated with aggressive disease and poorer prognosis in breast cancer patients; anti-HER2 antibodies inhibit growth in tumor cells that overexpress HER2
Topoisomerase I inhibitors bind to topoisomerase I-DNA complex and prevents ligation of the cleaved DNA strand; this results in double-strand DNA breaks, and ultimately, cell death and termination of cellular replication