Initial US Approval:
2019
Key Clinical Studies:
DESTINY-Breast06 (NCT04494425)
Drug Class/Description:
HER2-directed antibody and topoisomerase inhibitor conjugate
Boxed Warning: Interstitial Lung Disease and Embryo-Fetal Toxicity
- Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/ pneumonitis. Advise patients of the risk and to immediately report symptoms.
- Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.
Indications and Usage:
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate 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 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 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.*
- adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ ISH positive) gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
- 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.*
* These indications are 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.
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 HER2ultralow 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.
Dosage Forms and Strengths:
For injection: 100 mg lyophilized powder in a single-dose vial.
Contraindications:
None.
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).
Adverse Reactions:
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.
Use in Specific Populations:
- Lactation: Advise not to breastfeed.
- Females and Males of Reproductive Potential: Verify pregnancy status of females prior to initiation of ENHERTU.
Adapted From:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761139s032s035lbl.pdf
Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.
