Drug information of Famtrastuzumab


Fam-trastuzumab deruxtecan is used to treat HER2-positive breast cancer that has spread to other parts of the body (metastatic) or cannot be removed with surgery.

Fam-trastuzumab deruxtecan is usually given after 2 or more other treatments have failed.

Fam-trastuzumab deruxtecan was approved by the US Food and Drug Administration (FDA) on an "accelerated" basis. In clinical studies, some people responded to fam-trastuzumab deruxtecan, but further studies are needed.

Mechanism of effect

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


Fam-trastuzumab deruxtecan is a human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate composed of a humanized IgG1 monoclonal antibody, which has the same amino acid sequence as trastuzumab (and targets HER2), a cleavable tetrapeptide-based linker, and the cytotoxic component, a topoisomerase I inhibitor (Modi 2020). The deruxtecan component is a cleavable linker and the topoisomerase inhibitor, DXd (an exatecan derivative). Upon binding to HER2 on tumor cells, fam-trastuzumab deruxtecan undergoes internalization and intracellular linker cleavage by lysosomal enzymes, releasing DXd and resulting in DNA damage and cell death.



Vd: Fam-trastuzumab deruxtecan: 2.77 L.


Fam-trastuzumab deruxtecan: Degradation via catabolic pathways into small peptides and amino acids; DXd: Primarily via CYP3A4.


Clearance: Fam-trastuzumab deruxtecan: 0.42 L/day; DXd: 19.2 L/hour.

Half-Life Elimination

Fam-trastuzumab deruxtecan: ~5.7 days; DXd: 5.8 days.

Protein Binding

DXd: ~97% (to plasma proteins)

Drug indications

breast cancer , cancer


5.4 mg/kg IV every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity


 Bone marrow suppression: Severe neutropenia may occur, including grades 3 and 4 toxicity and neutropenic fever. The median time to first onset was 1.4 months (range: 0.3 to ~18 months). Monitor CBC prior to treatment initiation, prior to each dose, and as clinically indicated. Depending on the severity, neutropenia may require treatment interruption and/or dose reduction.

• Cardiotoxicity: Patients treated with fam-trastuzumab deruxtecan may be at increased risk of developing left ventricular dysfunction. Decreased left ventricular ejection fraction (LVEF) has been observed with anti-human epidermal growth factor receptor 2 (HER2) therapies, including fam-trastuzumab deruxtecan. Cases of asymptomatic LVEF decrease have been reported. Fam-trastuzumab deruxtecan has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to treatment initiation. Assess LVEF prior to fam-trastuzumab deruxtecan initiation and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. Permanently discontinue fam-trastuzumab deruxtecan if LVEF of <40% or absolute decrease from baseline of >20% is confirmed. Permanently discontinue fam-trastuzumab deruxtecan in patients with symptomatic heart failure.

• GI toxicity: Fam-trastuzumab deruxtecan is associated with moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]). Nausea, vomiting, constipation, and diarrhea were commonly reported with fam-trastuzumab deruxtecan, although were usually grade 1 or 2.

• Pulmonary toxicity: Interstitial lung disease: [US Boxed Warning]: Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with fam-trastuzumab deruxtecan. Monitor for and promptly investigate signs/symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue fam-trastuzumab deruxtecan in all patients with grade 2 or higher ILD/pneumonitis. Advise patients of the risk and the need to immediately report symptoms. The median time to first onset was 4.1 months (range: 1.2 to 8.3 months). ILD/pneumonitis may be severe or life-threatening. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor for signs/symptoms of ILD. Promptly investigate evidence of ILD, including radiographic imaging for suspected ILD. Consider consultation with a pulmonologist. For asymptomatic (grade 1) ILD, consider corticosteroid treatment (eg, ≥0.5 mg/kg prednisolone or equivalent, followed by a gradual taper if necessary); withhold fam-trastuzumab deruxtecan until recovery. For any symptomatic ILD (≥ grade 2), permanently discontinue fam-trastuzumab deruxtecan and promptly begin corticosteroid treatment (eg, ≥1 mg/kg prednisolone or equivalent) followed by gradual taper (over 4 weeks) upon improvement.

Points of recommendation

IV: Administer the first infusion over 90 minutes. If initial infusion was tolerated well, administer subsequent infusions over 30 minutes. Do not administer as an IV push or bolus. Administer only with an infusion set made of polyolefin or polybutadiene and a 0.2- or 0.22-micron in-line polyethersulfone or polysulfone filter. If refrigerated, allow solution to reach room temperature prior to administration. Slow or interrupt the infusion rate if infusion-related symptoms develop; discontinue permanently for severe infusion reactions. Do not administer with other drugs through the same IV line.

Fam-trastuzumab deruxtecan is associated with moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]).

Check label to ensure appropriate product is being administered; fam-trastuzumab deruxtecan, trastuzumab/hyaluronidase, conventional trastuzumab products, ado-trastuzumab emtansine, and pertuzumab/trastuzumab/hyaluronidase are different products and are NOT interchangeable.


Store intact vials at 2ºC to 8ºC (36ºF to 46ºF). Do not freeze. Store in the original carton (until time of reconstitution) to protect from light. Do not shake the reconstituted or diluted solution.

If not used immediately, store reconstituted vials at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours (from time of reconstitution). Do not freeze; protect from light. If not used immediately, store solutions diluted for infusion at room temperature for up to 4 hours (including preparation and infusion), or in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours. Do not freeze; protect from light.

Pregnancy level


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

Breast feeding warning

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

Drug forms


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