Enhertu (Trastuzumab Deruxtecan)
Antibody-Drug Conjugate for HER2-Targeted Cancer Treatment
Enhertu (trastuzumab deruxtecan) is a groundbreaking antibody-drug conjugate (ADC) used to treat several types of HER2-expressing cancers in adults, including breast cancer, non-small cell lung cancer, and gastric cancer. It works by delivering a potent chemotherapy payload directly to HER2-positive cancer cells. This guide covers uses, dosage, side effects, warnings, and storage based on EMA, FDA, and peer-reviewed clinical evidence.
Quick Facts: Enhertu
Key Takeaways
- Enhertu is an antibody-drug conjugate that combines a HER2-targeting antibody with a topoisomerase I inhibitor to deliver chemotherapy directly into cancer cells.
- It is approved for HER2-positive and HER2-low metastatic breast cancer, HER2-mutant non-small cell lung cancer, and HER2-positive gastric cancer.
- The most serious risk is interstitial lung disease (ILD), which can be life-threatening and requires immediate medical attention for any new respiratory symptoms.
- Enhertu is administered as an intravenous infusion every three weeks at a hospital or outpatient clinic under medical supervision.
- Effective contraception is required during treatment and for at least 7 months (women) or 4 months (men) after the last dose due to embryo-fetal toxicity.
What Is Enhertu and What Is It Used For?
Enhertu is a cancer medicine containing the active substance trastuzumab deruxtecan. It belongs to a class of drugs called antibody-drug conjugates (ADCs), which represent one of the most innovative approaches in modern oncology. The drug is composed of two key components: a monoclonal antibody based on trastuzumab that specifically binds to the HER2 (human epidermal growth factor receptor 2) protein on the surface of cancer cells, and a potent cytotoxic payload called DXd, which is a topoisomerase I inhibitor.
The mechanism of action is elegant in its design. When Enhertu binds to HER2 on the surface of a cancer cell, the entire drug-antibody complex is internalized into the cell through receptor-mediated endocytosis. Once inside the cell, enzymes called lysosomal cathepsins cleave the linker connecting the antibody to DXd, releasing the active chemotherapy agent. DXd then inhibits topoisomerase I, an enzyme essential for DNA replication, causing DNA damage and ultimately cancer cell death (apoptosis).
A particularly important feature of Enhertu is what scientists call the "bystander effect." Because DXd is membrane-permeable, it can diffuse out of the targeted cell and enter neighboring cancer cells that may have lower levels of HER2 expression. This bystander killing effect is one reason Enhertu has shown efficacy even in tumors classified as HER2-low, a category of cancer that was previously considered untreatable with HER2-targeted therapies.
Approved Indications
Enhertu is approved for the treatment of adult patients with the following conditions:
- HER2-positive metastatic breast cancer – For patients whose cancer has spread to other parts of the body or cannot be surgically removed, and who have received at least one prior HER2-targeted treatment regimen. The pivotal DESTINY-Breast03 trial demonstrated that Enhertu nearly doubled progression-free survival compared to trastuzumab emtansine (T-DM1).
- HER2-low or HER2-ultralow metastatic breast cancer – For patients whose cancer has spread or cannot be surgically removed and who have received prior chemotherapy. A test will be performed to confirm HER2-low or HER2-ultralow status. The DESTINY-Breast04 and DESTINY-Breast06 trials established this as a new treatment paradigm.
- HER2-mutant non-small cell lung cancer (NSCLC) – For patients with metastatic or unresectable NSCLC harboring activating HER2 mutations who have received at least one prior systemic therapy. The DESTINY-Lung02 trial demonstrated meaningful clinical benefit in this difficult-to-treat population.
- HER2-positive gastric cancer – For patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen. The DESTINY-Gastric01 and DESTINY-Gastric02 trials supported this indication.
Before starting Enhertu, your oncologist will order specific tests to determine the HER2 status of your tumor. These may include immunohistochemistry (IHC) and/or in situ hybridization (ISH) testing. The results of these tests determine whether Enhertu is appropriate for your specific cancer type and guide the treatment decision.
What Should You Know Before Receiving Enhertu?
Contraindications
Enhertu should not be given if you are allergic (hypersensitive) to trastuzumab deruxtecan or any of the other ingredients in this medicine, including L-histidine, L-histidine hydrochloride monohydrate, sucrose, and polysorbat 80. If you are not sure whether you are allergic, speak to your doctor or nurse before receiving Enhertu. Patients with known hypersensitivity to polysorbate 80 should inform their healthcare provider, as this excipient is present in the formulation and may cause allergic reactions in sensitive individuals.
Warnings and Precautions
Talk to your doctor or nurse before and during treatment with Enhertu if you experience any of the following serious conditions:
Interstitial lung disease (ILD), including cases with fatal outcomes, has been reported in patients treated with Enhertu. Symptoms include cough, shortness of breath, fever, or other new or worsening breathing problems. A history of lung disease or kidney problems may increase your risk of developing ILD. Your doctor will monitor your lungs throughout treatment. Report any new respiratory symptoms immediately, as early detection and management of ILD is critical. Treatment may need to be permanently discontinued if ILD develops.
- Neutropenia and infections – Enhertu can cause a decrease in neutrophils (a type of white blood cell), increasing the risk of serious infections. Symptoms may include chills, fever, mouth sores, abdominal pain, or pain during urination. Your doctor will regularly check your blood counts before and during treatment.
- Left ventricular dysfunction – Heart problems, including decreased ability of the heart to pump blood, have been reported. Symptoms include new or worsening shortness of breath, cough, fatigue, swollen ankles or legs, irregular heartbeat, sudden weight gain, dizziness, or loss of consciousness. Cardiac function should be assessed before and during treatment.
- Liver problems – Your doctor may need to monitor your liver function with blood tests during treatment with Enhertu. Report any symptoms such as yellowing of the skin or eyes, dark urine, or unexplained right-sided abdominal pain.
Your doctor will perform blood tests and other assessments before and during treatment to monitor for these potential complications. This typically includes complete blood counts, liver function tests, kidney function tests, cardiac assessments (such as echocardiography), and lung imaging studies when clinically indicated.
Children and Adolescents
Enhertu is not recommended for anyone under 18 years of age. This is because there is no data on how well the drug works or how safe it is in this age group. All clinical trials of Enhertu have been conducted in adult patients.
Drug Interactions
Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines. While the antibody component of Enhertu is not expected to have significant drug interactions, the DXd payload is metabolized by CYP3A4 enzymes. Strong CYP3A4 inhibitors may increase DXd exposure, while strong CYP3A4 inducers may decrease its effectiveness.
Pregnancy and Breastfeeding
Enhertu is not recommended during pregnancy because it may cause birth defects or harm to the developing fetus. Both the anti-HER2 antibody component and the DXd cytotoxic payload can potentially damage fetal tissue. If you are pregnant, think you might be pregnant, or are planning to become pregnant, tell your doctor immediately before or during treatment.
- Breastfeeding – You should not breastfeed during treatment with Enhertu and for at least 7 months after the last dose. It is not known whether Enhertu passes into breast milk, and a risk to the breastfed infant cannot be excluded.
- Contraception for women – Women of childbearing potential must use effective contraception during treatment and for at least 7 months after the last dose of Enhertu.
- Contraception for men – Male patients whose partners can become pregnant should use effective contraception during treatment and for at least 4 months after the last dose.
- Fertility – Enhertu may reduce fertility in men. Male patients should seek advice about sperm preservation before starting treatment. Do not father a child for at least 4 months after completing treatment.
Driving and Using Machines
Enhertu is not expected to significantly impair your ability to drive or operate machinery. However, use caution if you experience tiredness, dizziness, or headache, which are common side effects of the treatment. If you experience any of these symptoms, avoid driving or operating heavy machinery until they resolve.
How Does Enhertu Interact with Other Drugs?
The antibody component of Enhertu (trastuzumab) follows the typical metabolic pathway of monoclonal antibodies and is not significantly affected by cytochrome P450 enzymes or drug transporters. However, the cytotoxic payload DXd is a substrate of CYP3A4, and its exposure may be affected by co-administered drugs that inhibit or induce this enzyme. Your oncologist will review all your medications before starting Enhertu treatment.
| Interacting Drug/Class | Effect | Clinical Recommendation |
|---|---|---|
| Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin) | May increase DXd exposure and risk of adverse effects | Avoid concurrent use when possible; monitor closely for increased toxicity if unavoidable |
| Strong CYP3A4 inducers (e.g., rifampicin, phenytoin, carbamazepine, St. John's Wort) | May decrease DXd exposure and reduce efficacy | Avoid concurrent use; consider alternative treatments |
| Other HER2-targeted agents (e.g., trastuzumab, pertuzumab) | Potential overlapping HER2 binding and cardiac effects | Enhertu should not be combined with other anti-HER2 therapies outside clinical trials |
| Cardiotoxic agents (e.g., anthracyclines such as doxorubicin) | Increased risk of left ventricular dysfunction | Monitor cardiac function closely; cumulative anthracycline exposure should be assessed |
| Live vaccines | Risk of infection due to immunosuppression from treatment | Avoid live vaccines during treatment; inactivated vaccines may be given but immune response may be reduced |
This list is not exhaustive. Always inform your healthcare team about all medications you are taking, including prescription drugs, over-the-counter medicines, herbal supplements, and vitamins. Your oncology pharmacist can provide a comprehensive drug interaction review before you start treatment with Enhertu.
What Is the Correct Dosage of Enhertu?
Enhertu is administered exclusively at a hospital or outpatient oncology clinic under the supervision of a healthcare professional experienced in cancer treatment. The dose is calculated based on your body weight. Before each infusion, your doctor may give you pre-medications to help prevent nausea and vomiting, which are among the most common side effects.
| Indication | Recommended Dose | Frequency | Infusion Duration |
|---|---|---|---|
| HER2-positive breast cancer | 5.4 mg/kg | Every 3 weeks | 90 min (first), then 30 min |
| HER2-low / HER2-ultralow breast cancer | 5.4 mg/kg | Every 3 weeks | 90 min (first), then 30 min |
| HER2-mutant NSCLC | 5.4 mg/kg | Every 3 weeks | 90 min (first), then 30 min |
| HER2-positive gastric cancer | 6.4 mg/kg | Every 3 weeks | 90 min (first), then 30 min |
Administration
Enhertu is prepared by reconstituting the lyophilized powder and diluting it in a glucose 5% infusion bag. It is administered as an intravenous infusion using an in-line filter. It must not be given as an intravenous push or bolus injection. The first infusion is given over approximately 90 minutes. If the first infusion is well tolerated, subsequent infusions may be administered over 30 minutes.
Your doctor will decide how many treatment cycles you need based on how well the treatment is working and how well you tolerate it. Treatment typically continues until disease progression or unacceptable toxicity occurs.
Monitoring During Treatment
Before and during treatment with Enhertu, your healthcare team will perform regular monitoring that may include:
- Complete blood counts (CBC) to check white blood cells, red blood cells, and platelets
- Liver function tests (ALT, AST, bilirubin, alkaline phosphatase)
- Kidney function tests (creatinine)
- Cardiac assessments (echocardiography or MUGA scan) to monitor heart function
- Pulmonary monitoring and imaging as clinically indicated to detect early signs of ILD
Dose Modifications
Your doctor may need to reduce your dose, delay treatment, or permanently discontinue Enhertu depending on the type and severity of side effects you experience. Common reasons for dose modification include neutropenia, thrombocytopenia, ILD, and left ventricular dysfunction. Two dose reduction levels are generally available before treatment discontinuation is considered. Never adjust your treatment schedule without consulting your oncologist.
Missed Dose
If you miss a scheduled appointment for Enhertu, contact your doctor immediately to arrange a new appointment. It is very important not to miss any doses of this medicine. Your treatment team will work with you to reschedule the infusion as soon as possible and may adjust subsequent treatment timing accordingly.
Stopping Treatment
Do not stop receiving Enhertu without discussing it with your doctor. Stopping treatment prematurely could affect how well the medicine controls your cancer. If you have any concerns about continuing treatment, including side effects or quality of life considerations, discuss them openly with your oncology team.
What Are the Side Effects of Enhertu?
Like all medicines, Enhertu can cause side effects, although not everybody gets them. The type and severity of side effects can vary depending on the dose you receive and the type of cancer being treated. It is important to tell your doctor about any side effects you experience, including those not listed here, as some may require medical management or dose adjustments.
Contact your doctor or seek emergency medical care immediately if you experience any of the following: new or worsening cough, shortness of breath, or fever (possible ILD); chills, high fever, or signs of infection (possible febrile neutropenia); sudden breathlessness, chest pain, or swelling in the legs (possible cardiac or thromboembolic event).
Side Effect Frequency Overview
Very Common
May affect more than 1 in 10 patients
- Nausea and vomiting
- Fatigue and tiredness
- Decreased white blood cells (neutropenia, leukopenia)
- Decreased red blood cells (anemia)
- Decreased platelets (thrombocytopenia)
- Decreased appetite
- Hair loss (alopecia)
- Diarrhea
- Constipation
- Elevated liver enzymes (transaminases)
- Musculoskeletal pain
- Abdominal pain
- Weight loss
- Fever (pyrexia)
- Upper respiratory tract infection
- Headache
- Low potassium (hypokalemia)
- Mouth sores (stomatitis)
- Cough
- Indigestion (dyspepsia)
- Swelling of ankles and feet (peripheral edema)
- Interstitial lung disease / pneumonitis
- Neutropenic infection
- Left ventricular dysfunction
Common
May affect up to 1 in 10 patients
- Shortness of breath (dyspnea)
- Lung infection (pneumonia)
- Elevated bilirubin, alkaline phosphatase, or creatinine
- Nosebleed (epistaxis)
- Dizziness
- Skin rash
- Pancytopenia (decrease in all blood cell types)
- Altered or bad taste (dysgeusia)
- Dry eyes
- Itching (pruritus)
- Bloating (abdominal distension)
- Blurred vision
- Skin discoloration
- Thirst and dry mouth
- Febrile neutropenia
- Flatulence
- Gastritis (stomach inflammation)
- Infusion-related reactions (fever, chills, flushing, itching, rash)
Managing Side Effects
Your oncology team will provide comprehensive supportive care to help manage side effects. Anti-nausea medications (antiemetics) are typically given before each infusion. Growth factor support (G-CSF) may be used if neutropenia becomes severe. Regular blood tests help detect blood count changes early, allowing your doctor to adjust treatment before complications develop.
Many side effects are manageable and may improve as your body adjusts to treatment. However, some side effects, particularly ILD and severe neutropenia, require prompt medical intervention. Keep your oncology team informed about all symptoms, even those that seem minor, as early management leads to better outcomes.
It is important to report suspected side effects after the medicine has been authorized. This allows ongoing monitoring of the medicine's benefit-risk balance. Healthcare professionals and patients can report side effects to their national medicines regulatory authority (such as the FDA in the United States or the EMA in Europe).
How Should Enhertu Be Stored?
Enhertu is stored by healthcare professionals at the hospital or clinic where you receive treatment. You will not need to store this medicine at home. However, for reference, the storage conditions are as follows:
- Unopened vials: Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
- After reconstitution: The reconstituted solution is chemically and physically stable for up to 24 hours at 2°C to 8°C, protected from light. From a microbiological standpoint, it should be used immediately.
- Diluted infusion solution: If not used immediately, store at room temperature (not exceeding 30°C) for up to 4 hours including preparation and infusion time, or refrigerated at 2°C to 8°C for up to 24 hours, protected from light. Do not freeze.
- General precautions: Keep out of sight and reach of children. Do not use after the expiry date stated on the carton and vial after EXP. The expiry date refers to the last day of that month.
Any unused medicine or waste material should be disposed of in accordance with local regulations for handling cytotoxic agents. Do not throw away any medicines via wastewater or household waste. These measures help to protect the environment.
What Does Enhertu Contain?
Active Ingredient
The active substance is trastuzumab deruxtecan. Each single-use vial contains 100 mg of trastuzumab deruxtecan as a lyophilized (freeze-dried) powder. After reconstitution with 5 mL of sterile water for injection, each vial contains 5 mL of solution at a concentration of 20 mg/mL. Trastuzumab deruxtecan has a drug-to-antibody ratio (DAR) of approximately 8, meaning each antibody molecule carries approximately 8 DXd molecules.
Other Ingredients (Excipients)
- L-histidine (buffer)
- L-histidine hydrochloride monohydrate (buffer)
- Sucrose (stabilizer)
- Polysorbate 80 (E433) – surfactant; each 100 mg vial contains 1.5 mg of polysorbate 80
Appearance and Packaging
Enhertu is a white to yellowish-white lyophilized powder supplied in a clear, amber glass vial with a rubber stopper, aluminum seal, and plastic flip-off cap. Each carton contains 1 vial. The reconstituted solution should be clear and colorless to slightly yellow. Do not use the solution if it contains visible particles, is cloudy, or is discolored.
Marketing Authorization
Enhertu is manufactured by Daiichi Sankyo and co-developed with AstraZeneca. It was first approved by the FDA in December 2019 and subsequently by the EMA and other regulatory agencies worldwide. It has received conditional marketing authorization in some jurisdictions, meaning additional data from ongoing clinical trials is expected to further confirm its benefit-risk profile.
Frequently Asked Questions About Enhertu
Enhertu (trastuzumab deruxtecan) is used to treat adults with HER2-positive metastatic breast cancer after prior HER2-targeted therapy, HER2-low or HER2-ultralow metastatic breast cancer after prior treatment, HER2-mutant non-small cell lung cancer after prior therapy, and HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma after prior HER2-targeted therapy. Your oncologist will determine which indication applies to your cancer type based on biomarker testing.
The most serious side effects include interstitial lung disease (ILD) or pneumonitis, which can be fatal. Other serious side effects include severe neutropenia that can lead to life-threatening infections (febrile neutropenia), and left ventricular dysfunction (heart problems). Patients should report any new or worsening respiratory symptoms, fever, or signs of heart failure to their healthcare team immediately.
While both drugs target HER2, Enhertu is an antibody-drug conjugate (ADC) that combines a HER2-targeting antibody with a potent chemotherapy payload (DXd, a topoisomerase I inhibitor). This allows Enhertu to deliver cytotoxic therapy directly to HER2-expressing cancer cells. The bystander effect of DXd also enables Enhertu to treat HER2-low cancers, which trastuzumab alone cannot effectively target. Enhertu carries approximately 8 DXd molecules per antibody, making it a highly potent targeted therapy.
No. Enhertu is not recommended during pregnancy because it can harm the developing fetus. Women of childbearing potential must use effective contraception during treatment and for at least 7 months after the last dose. Men whose partners can become pregnant should use effective contraception during treatment and for at least 4 months after the last dose. Breastfeeding should also be avoided during treatment and for 7 months after the last dose.
In the landmark DESTINY-Breast04 trial, Enhertu significantly improved progression-free survival (median 9.9 months vs. 5.1 months) and overall survival (median 23.4 months vs. 16.8 months) compared to physician's choice chemotherapy in patients with HER2-low metastatic breast cancer. This was a paradigm-shifting result that established HER2-low as a treatable target and expanded treatment options for a large number of breast cancer patients who were previously not eligible for HER2-targeted therapy.
There is no predetermined fixed duration for Enhertu treatment. Your oncologist will continue treatment as long as it is controlling your cancer and you are tolerating it. Treatment is given in cycles of every 3 weeks and continues until disease progression, unacceptable toxicity, or the decision by you and your doctor to stop. Some patients receive Enhertu for many months to over a year. Regular imaging assessments will be used to evaluate treatment response.
References
- European Medicines Agency (EMA). Enhertu (trastuzumab deruxtecan) – Summary of Product Characteristics. Last updated 2025. Available at: ema.europa.eu/en/medicines/human/EPAR/enhertu
- U.S. Food and Drug Administration (FDA). Enhertu (fam-trastuzumab deruxtecan-nxki) Prescribing Information. Daiichi Sankyo, Inc. Revised 2024.
- Modi S, Saura C, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020;382(7):610-621. doi:10.1056/NEJMoa1914510
- Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer (DESTINY-Breast03). N Engl J Med. 2022;386(12):1143-1154. doi:10.1056/NEJMoa2115022
- Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer (DESTINY-Breast04). N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
- Li BT, Smit EF, Goto Y, et al. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer (DESTINY-Lung02). N Engl J Med. 2022;386(3):241-251. doi:10.1056/NEJMoa2112431
- Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer (DESTINY-Gastric01). N Engl J Med. 2020;382(25):2419-2430. doi:10.1056/NEJMoa2004413
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Breast Cancer. Version 2.2025.
- Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020;31(12):1623-1649.
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List, 2023.
Medical Editorial Team
Medical Review: iMedic Medical Review Board – Specialists in Oncology and Clinical Pharmacology
Evidence Level: 1A – Systematic reviews and meta-analyses of randomized controlled trials
Guidelines Followed: EMA SmPC, FDA Prescribing Information, NCCN Guidelines, ESMO Guidelines
Last Fact-Checked:
Disclosure: No commercial funding. Independent medical editorial content. No pharmaceutical company sponsorship or advertising. All content is reviewed according to international medical standards and the GRADE evidence framework.