Enhertu

Enhertu is a targeted cancer treatment used for breast cancer, stomach cancer, non-small cell lung cancer, and other solid tumors in certain patients with increased HER2 protein levels or HER2 gene changes. Enhertu works in two steps: it targets and binds to HER2 proteins on the surface of cancer cells, then releases a chemotherapy drug directly inside them to destroy them. Enhertu is a HER2-directed antibody-drug conjugate.

Enhertu is given as an intravenous (IV) infusion, usually every 3 weeks, with the first infusion taking approximately 90 minutes, and later infusions are usually given over 30 minutes if the first was well tolerated.

Enhertu was first FDA-approved on December 20, 2019. The most recent approvals were granted on May 15, 2026, expanding Enhertu's use into early-stage HER2-positive breast cancer for the first time, both before surgery (neoadjuvant) and after surgery (adjuvant).

Enhertu contains the active ingredient fam-trastuzumab deruxtecan-nxki. It is NOT the same medicine as trastuzumab (Herceptin, Kanjinti, Ogivri, and others) or ado-trastuzumab emtansine (Kadcyla). Do not substitute one for another.

Enhertu is FDA-approved for use in adults with:

HER2-positive early breast cancer

• Neoadjuvant (pre-surgery) treatment: Enhertu cycles are given before surgery in adults with HER2-positive (IHC 3+ or ISH+) Stage II or Stage III breast cancer, followed by cycles of a taxane, trastuzumab, and pertuzumab (THP). Patients must be identified by an FDA-authorized test.
• Adjuvant (post-surgery) treatment: Enhertu is given after surgery in adults with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease remaining after neoadjuvant treatment with trastuzumab (with or without pertuzumab) and taxane-based chemotherapy.

HER2-positive metastatic breast cancer

• First-line treatment: In combination with pertuzumab for adults with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have not previously been treated, that has been determined by an FDA-authorized test
• Previously treated: As monotherapy for adults with unresectable or metastatic HER2-positive breast cancer (IHC 3+ or ISH+) who previously received anti-HER2 therapy, and whose cancer returned during treatment or within 6 months of completing therapy.

HER2-low and HER2-ultralow metastatic breast cancer - monotherapy

• HR-positive, HER2-low or HER2-ultralow: For adults 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 that has progressed on one or more endocrine therapies in the metastatic setting, as confirmed by an FDA-authorized test.
• HER2-low: For adults with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have already received chemotherapy in the metastatic setting, and whose cancer returned during or within 6 months of completing adjuvant chemotherapy.

HER2-mutant non-small cell lung cancer (NSCLC) - monotherapy

• Adults with unresectable or metastatic non-small cell lung cancer with activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, who have already received at least one systemic therapy. (Accelerated approval)

HER2-positive advanced stomach cancer - monotherapy

• Adults with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have already received a trastuzumab-based regimen.

HER2-positive (IHC 3+) solid tumors - monotherapy

• Adults with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options. (Accelerated approval)

Enhertu is both a chemotherapy and a targeted therapy, a combination called an antibody-drug conjugate (ADC). Its active ingredient, fam-trastuzumab deruxtecan-nxki, joins two cancer-fighting agents:

• Fam-trastuzumab — the targeted therapy component, which seeks out and attaches to HER2 proteins on cancer cells
• Deruxtecan (DXd) — the chemotherapy component, which is released inside the cancer cell to kill it

Enhertu has been described as having a "bystander effect", where the chemotherapy payload can spread from targeted cells to nearby cancer cells, even those with low or no HER2 expression, giving it broader anti-tumor activity to tumor cells, even those that have little or no HER2.

HER2 (human epidermal growth factor receptor 2) is a protein that normally helps control cell growth. In some cancers, the HER2 gene produces too many copies of this protein and they are called HER2-positive cancers. HER2-positive tumors tend to grow faster and are more likely to spread than HER2-negative cancers.

The IHC scoring system (0, 1+, 2+, 3+) is used to measure HER2 levels in tumor samples:

• HER2-positive (IHC 3+ or ISH+): High HER2 protein levels — the classic target for drugs like Enhertu
• HER2-low (IHC 1+ or IHC 2+/ISH-): Low but detectable HER2 — previously classified as HER2-negative, but Enhertu has shown benefit in this group
• HER2-ultralow (IHC 0 with membrane staining): Very low HER2 expression — Enhertu is now approved for HR-positive metastatic breast cancer in this category

HER2 testing is required before starting Enhertu. Your oncologist will arrange testing on a tumor sample to determine your HER2 status.

Enhertu is given as an infusion into a vein by your healthcare provider.

Enhertu is usually given once every 3 weeks in a 21-day treatment cycle. The first infusion will take over 90 minutes, but your next infusions are usually given over 30 minutes.

The dose you will receive will depend on how much you weigh and your type of cancer.

During an infusion, it is possible to have an infusion-related reaction. If this happens, your healthcare provider may slow down or temporarily stop your infusion, if you have a severe infusion reaction, your healthcare provider may stop this treatment permanently.

Your doctor will determine how long to treat you with this medicine. If you develop side effects or your cancer progresses, your dose may be reduced, and treatment may be paused or even stopped.

Enhertu may make you feel sick, and you may vomit. Your doctor may prescribe a medicine to prevent nausea and vomiting.

You will need frequent medical tests.

Boxed warnings

Enhertu has boxed warnings for embryo-fetal toxicity and for interstitial lung disease (ILD) and pneumonitis and embryo-fetal toxicity. A boxed warning is the strongest safety-related warning issued by the FDA.

Lung problems (ILD/Pneumonitis): Enhertu can cause serious, life-threatening, or fatal lung injury. Interstitial lung disease (ILD) and pneumonitis have been reported in approximately 10–12% of patients at the standard 5.4 mg/kg dose. Report any new or worsening cough, shortness of breath, fever, or breathing changes to your doctor immediately. If Grade 2 or higher ILD/pneumonitis is confirmed, Enhertu must be permanently discontinued.

Embryo-fetal toxicity: Enhertu can seriously harm an unborn baby. Women must use effective contraception during treatment and for 7 months after the last dose. Men must use contraception during treatment and for 4 months after the last dose. A pregnancy test is required before starting treatment.

Other warnings

Neutropenia (low white blood cell counts): Low white blood cell counts are common with Enhertu and can increase the risk of serious infection. Blood counts are checked before every dose. Dose delays or reductions may be required.

Heart problems (Left Ventricular Dysfunction): This medicine may affect heart function. Your doctor will assess your heart's ejection fraction (LVEF) before starting treatment and monitor it regularly. Report any new shortness of breath, swelling, or palpitations to your doctor.

Enhertu (fam-trastuzumab deruxtecan) is not the same medicine as trastuzumab (Herceptin, Herzuma, Kanjinti, Ogivri, Ontruzant, Trazimera). These medicines contain only trastuzumab, they do not contain topoisomerase I inhibitor.

Enhertu (fam-trastuzumab deruxtecan-nxki) is not the same medicine as Kadcyla (ado-trastuzumab emtansine), which has a different antibody-drug conjugate.

Before starting this medicine, you should tell your healthcare provider about all of your medical conditions, especially if you:

• have any lung or breathing issues
• have symptoms or signs of infection
• have or have had in the past any heart problems

You may need to have a negative pregnancy test before starting this treatment.

Pregnancy

Enhertu can harm an unborn baby if the mother or the father is using this medicine. You should not take Enhertu if you are pregnant or planning a pregnancy, as it can harm your unborn baby.

If you are a woman and you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with this medicine. Females who are able to become pregnant should use effective birth control (contraception) during treatment with this medicine and for at least 7 months after the last dose.

If you are a man who has a female partner that is able to become pregnant, you should use effective birth control (contraception) during treatment with Enhertu and for at least 4 months after the last dose.

This medicine may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare provider if you have concerns about fertility.

Breastfeeding

Enhertu and breastfeeding:

• It is not known if Enhertu passes into your breast milk.
• Do not breastfeed during treatment with Enhertu and for 7 months after the last dose.

Common Enhertu side effects

Common Enhertu side effects may include hair loss, nausea, vomiting, loss of appetite, diarrhea, constipation, cough, fever, tiredness (fatigue), muscle and joint pain, low blood cell counts, low potassium, and abnormal liver function tests.

These common side effects occurred in 20% or more of patients on Enhertu during the DESTINY-Breast03 (NCT03529110) clinical trials.

The most common Enhertu side effects are gastrointestinal side effects, with 76% of patients having nausea and 49 % of patients having vomiting in the DESTINY-Breast03 trial. Your healthcare provider will give you medicines before your infusion to help prevent nausea and vomiting, and you may be prescribed nausea and vomiting medications to take at home. Talk to your HCP if you are experiencing problems with vomiting, nausea, constipation, or diarrhea.

Enhertu and hair loss

Often, people who have cancer treatment ask if their treatment will cause hair loss (alopecia).In the Enhertu clinical trial, 37% of patients had hair loss (DESTINY-Breast03). This ranged from thinning hair and patchy loss to complete hair loss. The good news is that hair loss is usually temporary and often begins to grow back after treatment ends.

Serious Enhertu side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling other serious side effects. Call your doctor at once if you have:

• chest tightness, wheezing, cough, new or worsening shortness of breath;
• pounding heartbeats or fluttering in your chest;
• fever, tiredness, dizziness;
• swelling in your lower legs, sudden weight gain;
• a light-headed feeling, like you might pass out;
• low blood cell counts - fever, chills, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands, and feet; or
• low potassium level - leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Managing Enhertu side effects

You may be prescribed medicine to prevent nausea and vomiting.You will need medical tests frequently to check blood counts.Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

HER2-Positive Early Breast Cancer – Post Neoadjuvant Treatment (monotherapy)

• 5.4 mg/kg every 3 weeks for 14 cycles unless disease recurrence or unacceptable toxicity

HER2-Positive, HER2-Low, or HER2- Ultralow Metastatic Breast Cancer (monotherapy)

• 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity

HER2-Mutant Unresectable or Metastatic NSCLC (monotherapy)

• 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity

HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors as monotherapy

• 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity

HER2-Positive Locally Advanced or Metastatic Gastric Cancer as monotherapy

• 6.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity

HER2-Positive Metastatic Breast Cancer in combination with pertuzumab

• Cycle 1, Day 1: Enhertu 5.4 mg/kg, followed by pertuzumab 840 mg. Pertuzumab should be administered 30 minutes after Enhertu.
• Subsequent cycles, Day 1: Enhertu 5.4 mg/kg, followed by pertuzumab 420 mg every 3 weeks
• Treatment continues until disease progression or unacceptable toxicity

HER2-Positive Early Breast Cancer followed by THP

• Enhertu 5.4 mg/kg every 3 weeks for 4 cycles, followed by THP regimen for 4 cycles
• THP regimen: a taxane concurrent with trastuzumab (6 mg/kg every 3 weeks) and pertuzumab (an initial dose of 840 mg followed by 420 mg every 3 weeks)

Comments:

• Administer the first infusion over 90 minutes; administer subsequent infusions over 30 minutes if prior infusions were well tolerated.
• Slow or interrupt the infusion rate if the patient develops infusion-related symptoms.
• Permanently discontinue therapy for severe infusion reactions.
• Dose modifications should occur in renal or liver impairment and due to adverse reactions.
• Check detailed dosing information on the Enhertu Dose page or the Prescribing Information

If you miss an appointment for your infusion, call your doctor to reschedule an appointment. Do not wait until the next planned treatment cycle.

Since this medicine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Some medications interact with Enhertu, so it is important to tell your doctor about any medicines that you are currently taking, or if you start or stop any medicine while you are having cancer treatment. Also tell your doctor about any vaccinations, over-the-counter medicines, vitamins, minerals or herbal products that you take.

Enhertu J-code is J9358, 1 mg fam-trastuzumab deruxtecan-nxki.J codes are used for medicines that are not taken orally and include injections, inhalations, and chemotherapies. J codes are important for accurate and consistent coding for billing and reimbursement purposes.

Your physician will need the Enhertu J-code when filling out forms for your treatment.

• Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
• Store in the original carton to protect it from light until the time of reconstitution.
• Do not shake the reconstituted or diluted solution.

Active Ingredient: fam-trastuzumab deruxtecan-nxki.

Inactive Ingredients: L-histidine, L-histidine hydrochloride monohydrate, polysorbate 80, and sucrose.

Enhertu is manufactured by: Daiichi Sankyo, Inc., Basking Ridge, NJ 07920 U.S. License No. 2128.

Enhertu is marketed by: Daiichi Sankyo, Inc., Basking Ridge, NJ 07920 and AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850.