Fam-trastuzumab deruxtecan-nxki (Enhertu) has been approved to treat unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer in patients who have received two or more prior anti-HER2-based regimens after the cancer metastasized. Enhertu is a HER2-directed antibody and topoisomerase inhibitor conjugate given as an IV infusion. It causes DNA damage and programmed cell death.

Enhertu's safety was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of the drug. Twenty percent of patients experienced a significant adverse effect. Enhertu's efficacy was assessed in a multicenter, single-arm trial that enrolled 184 female patients with HER2-positive, unresectable and/or metastatic breast cancer who had received two or more prior anti-HER2 therapies. The objective response rate (defined as the percentage of patients with a reduction in tumor burden of a predefined amount) was 60.3%, and the duration of response was a median 14.8 months.

Enhertu's approval was accelerated based on tumor response and duration of response, although clinical benefit has not yet been determined. The drug should not be substituted for or with trastuzumab (Herceptin) or ado-trastuzumab emtansine (Kadcyla), also used to treat HER2-positive breast cancer.

Enhertu has boxed warnings for interstitial lung disease and pneumonitis, which can be fatal, and for embryo-fetal toxicity because it is genotoxic and targets actively dividing cells. Other warnings and precautions include the risk of neutropenia and left ventricular dysfunction. The most common adverse effects are nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, cough, and thrombocytopenia.

Enhertu is given once every three weeks until either the disease progresses or there is unacceptable toxicity. Nurses should be careful to administer Enhertu only as an infusion, never as an IV bolus. The first infusion should be given over 90 minutes; if the patient tolerates Enhertu without infusion-related symptoms, subsequent doses can be given over 30 minutes. The nurse should slow or temporarily interrupt the infusion if infusion-related symptoms occur (for example, pruritus, urticaria, fever, rigors/chills, diaphoresis, bronchospasms, or cardiovascular collapse). The Food and Drug Administration (FDA) recommends discontinuation if infusion reactions are severe. If the Enhertu dose is decreased because of adverse effects, it shouldn't be increased again.

Patients should be assessed for possible interstitial lung disease and pneumonitis; those who develop signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms need to be closely evaluated. If the patient is diagnosed with grade 2 or higher interstitial lung disease or pneumonitis, Enhertu should be permanently discontinued. Women of childbearing age should be taught the risks of embryo-fetal harm and use effective contraception. Nurses should confirm that a complete blood count has been performed prior to Enhertu treatment and before each infusion to assess for neutropenia. Nurses should also confirm that left ventricular ejection fraction has been assessed prior to treatment; the FDA recommends the drug be stopped permanently if the patient has symptomatic congestive heart failure.

For complete prescribing information for Enhertu, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761139s000lbl.pdf.