fam-trastuzumab deruxtecan

High Alert

Unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ or ISH+) breast cancer in patients who have previously received an anti-HER2-based regimens either in the metastatic setting or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 mo of completing therapy.
Unresectable or metastatic hormone receptor-positive HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer that has progressed on ≥1 endocrine therapies in the metastatic setting.
Unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer in patients who have previously received chemotherapy in the metastatic setting or developed disease recurrence during or within 6 mo of completing adjuvant chemotherapy.
Locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction adenocarcinoma in patients who have previously received a trastuzumab-based regimen.
Unresectable or metastatic non-small cell lung cancer (NSCLC) in patients whose tumors have activating HER2 (ERBB2) mutations and who have received a prior systemic therapy.
Unresectable or metastatic HER2-positive (IHC 3+) solid tumors in patients who have received prior systemic treatment and have no satisfactory alternative treatment options.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB:
Pregnancy
;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment;
Severe hepatic impairment (total bilirubin >3–10 times upper limit of normal [ULN] or AST > ULN);
Rep:
Women of reproductive potential and men with female partners of reproductive potential
;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may have ↑ risk of adverse reactions.

Exercise Extreme Caution in:

Pre-existing cardiac dysfunction.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ↓left ventricular ejection fraction (LVEF), HF

Derm: alopecia, rash

EENT: dry eye, epistaxis

F and E: hypokalemia

GI: ↓appetite, ↑liver enzymes, abdominal pain, constipation, diarrhea, dyspepsia, nausea, stomatitis, vomiting

GU: ↓fertility (men)

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia

Neuro: dizziness, fatigue, headache

Resp: cough, dyspnea, interstitial lung disease (ILD)/pneumonitis, upper respiratory tract infection

Interactions ⬆ ⬇

Drug-drug:

None reported.

Availability ⬆ ⬇

Lyophilized powder for injection: 100 mg/vial

Route/Dosage ⬆ ⬇

Do NOT substitute fam-trastuzumab deruxtecan with trastuzumab or ado-trastuzumab emtansine.

Metastatic Breast Cancer, Unresectable/Metastatic Non-Small Cell Lung Cancer, or Unresectable/Metastatic Solid Tumors

IV (Adults ): 5.4 mg/kg every 3 wk; continue until disease progression or unacceptable toxicity.

Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

IV (Adults ): 6.4 mg/kg every 3 wk; continue until disease progression or unacceptable toxicity.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as a 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 linker, and a topoisomerase I inhibitor (DXd) (the cytotoxic component that causes DNA damage and apoptosis).

Therapeutic effects:

Regression of breast cancer and metastases.
Improved survival in gastric or gastroesophageal junction adenocarcinoma.
Decreased spread of NSCLC.

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, enzyme inhibitors

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to extravascular tissues.

Protein Binding: 97%.

Metabolism/Excretion: Monoclonal antibody component is degraded into smaller peptides via catabolism. DXd primarily metabolized by the liver via CYP3A4 isoenzyme. Excretion pathway unknown.

Half-Life: Fam-trastuzumab deruxtecan: 5.7 days; DXd: 5.8 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	unknown	unknown

Patient/Family Teaching ⬆ ⬇

Explain purpose of therapy to patient. Advise patient to read Medication Guide before starting therapy.
Advise patient to notify health care provider immediately if signs and symptoms of lung problems (cough, trouble breathing, shortness of breath, fever) occur.
Advise patient to notify health care provider immediately if signs and symptoms of infection (fever, chills) or heart problems (new or worsening shortness of breath, coughing, feeling tired, swelling of ankles or legs, irregular heartbeat, sudden weight gain, dizziness or light-headedness, loss of consciousness) occur.
Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Rep:
May cause fetal harm. Advise women of reproductive potential to use effective contraception and avoid breastfeeding during therapy and for ≥7 mo after last dose. Advise men with female partners of reproductive potential to use effective contraception during and for ≥4 mo after last dose. May impair male fertility.

section name header

Indications ⬇