Daiichi Sankyo/AstraZeneca Enhertu (fam-trastuzumab deruxtecan-nxki) Monograph

Published: July 18, 2025

Enhertu (fam-trastuzumab deruxtecan-nxki) is a prescription medication used for treating patients with certain types of cancer. Beginning with its first approval in 2019, Enhertu has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of certain types of breast cancers, gastric cancers, non-small cell lung cancers, and metastatic HER2-positive solid tumors.

Medication Overview:

Brand Name: Enhertu
Generic Name: fam-trastuzumab deruxtecan-nxki
Treatment for: Breast cancer, lung cancer, gastric or gastroesophageal junction adenocarcinoma, solid tumors
Manufacturer(s): Daiichi Sankyo, AstraZeneca
FDA Approval: Multiple approvals, 2019–2025

Indicated Condition	Indication	Age	Date Approved
HER2-Positive Unresectable or Metastatic Breast Cancer Following Two or More Prior Anti-HER2 Based Regimens	indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either: in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy	Adult	December 2019
Previously Treated HER2 Positive Advanced Gastric Cancer	ENHERTU is indicated for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.	Adult	January 2021
HER2-Positive Metastatic Breast Cancer Treated with a Prior Anti-HER2-Based Regimen	Enhertu is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.	Adult	May 2022
HER2-Low Metastatic Breast Cancer	Enhertu is indicated for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.	Adult	August 2022
Previously Treated HER2-Mutant Metastatic Non-Small Cell Lung Cancer	Enhertu is indicated for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.	Adult	August 2022
Previously Treated Patients with Metastatic HER2-Positive Solid Tumors	Enhertu is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.	Adult	August 2024
HER2-Low or HER2-Ultralow Metastatic Breast Cancer	Indicated for the treatment of adult patients with unresectable or metastatic: hormone receptor (HR)-positive HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting. HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.	Adult	January 2025

Warnings and Precautions:

Neutropenia: Monitor complete blood counts prior to initiation of Enhertu and prior to each dose, and as clinically indicated. Manage through treatment interruption or dose reduction.
Left Ventricular Dysfunction: Assess LVEF prior to initiation of Enhertu and at regular intervals during treatment as clinically indicated. Manage through treatment interruption or discontinuation. Permanently discontinue Enhertu in patients with symptomatic congestive heart failure (CHF).
Interstitial Lung Disease/Pneumonitis: Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with Enhertu
Neutropenia: Severe neutropenia, including febrile neutropenia, can occur in patients treated with Enhertu.
Left Ventricular Dysfunction: Patients treated with Enhertu may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including Enhertu.
Embryo-Fetal Toxicity: Based on its mechanism of action, Enhertu can cause fetal harm when administered to a pregnant woman. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Dosage and Administration:

Do not substitute Enhertu for or with trastuzumab or ado-trastuzumab emtansine.
For intravenous infusion only. Do not administer as an intravenous push or bolus. DO NOT use Sodium Chloride Injection, USP.
Premedicate for prevention of chemotherapy-induced nausea and vomiting.
The recommended dosage of Enhertu for HER2-positive, HER2-low, or HER2-ultralow breast cancer, HER2-mutant NSCLC, and HER2-positive (IHC 3+) solid tumors is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
The recommended dosage of Enhertu for HER2-positive gastric cancer is 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
Management of adverse reactions (ILD, neutropenia, thrombocytopenia, or left ventricular dysfunction) may require temporary interruption, dose reduction, or discontinuation of Enhertu.

Contraindications:

There are no contraindications listed.

Adverse Reactions:

The following clinically significant adverse reactions are described elsewhere in the labeling: Interstitial lung disease/pneumonitis, neutropenia, left ventricular dysfunction.

The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with:

HER2-positive, HER2-low, and HER2-ultralow metastatic breast cancer, HER2-mutant NSCLC, and HER2-positive (including IHC 3+) solid tumors are decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, decreased lymphocyte count, fatigue, decreased platelet count, increased aspartate aminotransferase, increased alanine aminotransferase, increased blood alkaline phosphatase, vomiting, alopecia, constipation, decreased blood potassium, decreased appetite, diarrhea, and musculoskeletal pain.
HER2-positive gastric cancer are decreased hemoglobin, decreased white blood cell count, decreased neutrophil count, decreased lymphocyte count, decreased platelet count, nausea, decreased appetite, increased aspartate aminotransferase, fatigue, increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhea, decreased blood potassium, vomiting, constipation, increased blood bilirubin, pyrexia, and alopecia.

Related Guidelines:

ASCO’s Systemic Treatment of Patients with Metastatic Breast Cancer
- Summary | Full Text
ASCO’s Therapy for Stage IV Non-Small-Cell Lung Cancer with Driver Alterations
- Summary | Full Text
ASCO’s Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer
- Summary | Full Text

Please note: This article is current as of July 9, 2025. Consult our clinical guidelines library or drug information tool to ensure you always have the most up-to-date information.