• Unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer in patients who have previously received ≥2 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 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 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.

Contraindicated in:

• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Severe renal impairment (CCr <30 mL/min)
• Severe hepatic impairment (total bilirubin >3–10× 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.

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

Derm: alopecia, rash.

EENT: dry eye, epistaxis.

F and E: hypokalemia.

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

GU: ↓ fertility (males).

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia.

Metab: ↓ appetite.

Neuro: dizziness, fatigue, headache.

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

Drug-Drug:

• None reported.

• Lyophilized powder for injection: 100 mg/vial;

Metastatic Breast Cancer or Unresectable/Metastatic Non-Small Cell Lung Cancer

• 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.

Enhertu

• 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).

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

Therapeutic Classification: antineoplastics

Pharmacologic Classification: monoclonal antibodies, enzyme inhibitors

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.

(plasma concentrations)

• Explain purpose of therapy to patient. Advise patient to read Medication Guide before starting therapy.
• Advise patient to notify health care professional immediately if signs and symptoms of lung problems (cough, trouble breathing or shortness of breath, fever, other new or worsening breathing symptoms [chest tightness, wheezing), 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 feeling lightheaded, loss of consciousness) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 7 mo after last dose. Advise males with female partners of reproductive potential to use effective contraception during and for at least 4 mo after last dose. May impair male fertility.

fam tras-TU-zoo-mab de-RUX-te-can