Enhertu (fam-trastuzumab-deruxtecan) is a s a HER2-directed antibody and topoisomerase inhibitor conjugate that is used to treat types of breast cancer,  stomach cancer and non-small cell lung cancer that have specific HER2 gene mutations. 

Enhertu works by blocking HER2 receptors on cancer cells to prevent cancer cells from multiplying, which slows the cancer growth and progression, and then its second action is to damage or kill the cancer cells.

Enhertu is made up of two cancer-fighting medicines joined together, a monoclonal antibody (fam-trastuzumab) and a chemotherapy drug (topoisomerase I inhibitor). Enhertu is an HER2-directed antibody and topoisomerase inhibitor conjugate.

Enhertu is an HER2 inhibitor which is a targeted therapy used to treat cancer. The FDA first approved Enhertu on December 20, 2019.

What is Enhertu used for?

Enhertu is FDA-approved for use in adult patients who have:

Breast cancer that is (HER2)-positive that is not removable by surgery or has spread and has already had a specific anti-HER2-based regimen.

Breast cancer that is HER2-low (IHC 1+ or IHC 2+/ISH-) that is not removable by surgery or has spread to other parts of your body, and who have already had chemotherapy for cancer that has spread or cancer has returned within 6 months of finishing adjuvant chemotherapy. 

Stomach cancer that is HER2-positive that is gastric or gastroesophageal junction (GEJ) adenocarcinoma cancer, and you have already had a trastuzumab-based regimen and cancer has spread to areas near your stomach (locally advanced) or has spread to other parts of your body (metastatic).

Non-small cell lung cancer (NSCLC) that has activating HER2 (ERBB2) mutations that cannot be removed by surgery or cancer that has spread to other parts of your body (metastatic), and you have already had systemic therapy, and activating HER2 (ERBB2) mutations have been detected by an FDA-approved test.

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

What is the HER2 gene?

Some cancer cells have too many copies of the human epidermal growth factor receptor 2 (HER2) gene, which makes a protein called the HER2, these cancers are called HER2 positive.  HER2 is a protein that controls cell growth, if your cancer is HER2 positive, it means it will more likely grow faster, spread, or come back.  Some cancer cells that are HER2-negative still have a number of HER2 proteins on the surface of the cells, these cancer cells are called HER2-low. Cancer medicines like Enhertu block HER2 receptors to reduce the ability of the cancer to grow and spread.

Enhertu can cause serious or life-threatening side effects on your heart or lungs. Call your doctor right away if you have a cough, tiredness, dizziness, chest tightness, wheezing, irregular heartbeats, new or worsening shortness of breath.

Enhertu can weaken (suppress) your immune system, and you may get an infection or bleed more easily. Tell your doctor if you have unusual bruising or bleeding or signs of infection (fever, chills, weakness, cold or flu symptoms, frequent or recurring illness).

Both men and women using this medicine should use effective birth control to prevent pregnancy. Birth control should be continued for 7 months after the last dose of Enhertu in women and 4 months after in men.

Your doctor will perform blood tests to make sure you do not have conditions that would prevent you from safely using this medicine.

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.

Usual Adult Dose Unresectable Metastatic Breast Cancer:

• 5.4 mg/kg IV every 3 weeks (21-day cycle) given as an intravenous infusion until disease progression or unacceptable toxicity.

Usual Adult Dose for Unresectable or Metastatic HER2-Mutant NSCLC:

• 5.4 mg/kg IV every 3 weeks (21-day cycle) given as an intravenous infusion until disease progression or unacceptable toxicity.

Usual Adult Dose for Locally Advanced or Metastatic Gastric Cancer

•  6.4 mg/kg given every 3 weeks (21-day cycle) given as an intravenous infusion  until disease progression or unacceptable toxicity.

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.

For more information on Enhertu dosing information click the link below.

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.

If you miss an appointment for your injection 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.

Common Enhertu side effects may include:

• nausea, vomiting, loss of appetite;
• diarrhea, constipation;
• cough;
• fever, feeling tired;
• low blood cell counts;
• low potassium;
• abnormal liver function tests; or
• hair loss.

Serious Enhertu side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Enhertu may cause 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.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

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 FDA at 1-800-FDA-1088.

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.