Trastuzumab deruxtecan

Trastuzumab deruxtecan (Enhertu) is a treatment for breast cancer, advanced stomach cancer, non-small cell lung cancer, and solid tumors with HER2 gene mutations in certain patients. Trastuzumab deruxtecan may help people with cancer live longer and delay the progression of their disease.

The active ingredient, fam trastuzumab deruxtecan nxki, is commonly shortened to trastuzumab deruxtecan or T-DXd.

Trastuzumab deruxtecan combines targeted therapy and chemotherapy into one treatment, known as an antibody-drug conjugate (ADC). The targeted therapy part, fam-trastuzumab (T), recognizes and attaches to HER2-positive cancer cells to help block their ability to grow and multiply. Once attached, the chemotherapy component, deruxtecan (DXd), is released inside the cancer cells, destroying them.

Trastuzumab deruxtecan mechanism of action is a HER2-directed antibody-drug conjugate.

Trastuzumab deruxtecan FDA approval for breast cancer was granted on December 20, 2019, for specific types of breast cancer, and since then the FDA approval extended to cover other conditions. Trastuzumab deruxtecan is approved under the brand name Enhertu by Daiichi Sankyo, Inc.,

Your healthcare provider will perform a test to make sure trastuzumab dextran is right for you. Trastuzumab dextran is FDA-approved to treat the following cancer types.

HER2-Positive Breast Cancer:

• HER2-positive Stage II or III early breast cancer followed by a taxane, trastuzumab, and pertuzumab (THP) before surgery. Your healthcare provider will perform a test to make sure this medicine is right for you.
• HER2-positive breast cancer that cannot be removed by surgery or has metastasized, in combination with pertuzumab as your first treatment. Your healthcare provider will perform a test to make sure this medicine is right for you.
• HER2-positive early breast cancer in patients who have received trastuzumab (with or without pertuzumab) and taxane-based treatment before surgery, and have cancer remaining in the tissue removed during surgery. Trastuzumab dextran is used as monotherapy.
• HER2-positive breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received a prior anti-HER2 breast cancer treatment: for metastatic disease, or have breast cancer that has come back during or within 6 months of completing treatment for their early-stage breast cancer.
• HER2-low breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received prior chemotherapy: for metastatic disease, or whose disease has returned during or within 6 months of completing adjuvant chemotherapy (after surgery). Your healthcare provider will perform a test to make sure this medicine is right for you.
• Hormone receptor (HR)-positive, HER2-low or HR-positive, HER2-ultralow breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received one or more endocrine treatments for metastatic disease. Your healthcare provider will perform a test to make sure this medicine is right for you.

Non-Small Cell Lung Cancer (NSCLC):

• Unresectable or Metastatic HER2-Mutant NSCLC: For adults whose non-small cell lung cancer cannot be surgically removed or has spread, with tumors exhibiting activating HER2 (ERBB2) mutations, and who have received prior systemic therapy.

Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma:

• Locally Advanced or Metastatic HER2-Positive Gastric Cancer: For adults with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or GEJ adenocarcinoma who have received a prior trastuzumab-based regimen.

HER2-Positive Solid Tumors:

• Unresectable or Metastatic HER2-Positive Solid Tumors: For adults with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior chemotherapy treatment and have no satisfactory alternative treatment options.

Some cancer cells have extra copies of the HER2 gene, which produces a protein called HER2. When this happens, the cancer is classified as HER2-positive. HER2 plays a key role in controlling cell growth, so HER2-positive cancers tend to grow faster, spread more easily, and have a higher chance of returning.

Even some HER2-negative cancers can still have low levels of HER2 protein on their surface - these are known as HER2-low cancers.

Trastuzumab deruxtecan works by binding to HER2 receptors, damaging the cancer cell, which slows down cancer growth and prevents it from spreading.

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

Trastuzumab deruxtecan 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.

Trastuzumab deruxtecan 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.

Trastuzumab deruxtecan 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, or new or worsening shortness of breath.

Trastuzumab deruxtecan 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 Trastuzumab deruxtecan 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.

Trastuzumab deruxtecan (fam-trastuzumab deruxtecan-nxki) 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

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

If you are a woman and you can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with this medicine. Females who can 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 can become pregnant, you should use effective birth control (contraception) during treatment with trastuzumab deruxtecan 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

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

Common trastuzumab deruxtecan side effects

Common trastuzumab deruxtecan 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 trastuzumab deruxtecan during clinical trials.

Serious trastuzumab deruxtecan 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.

Side effect management

Anti-nausea medicine may be prescribed to help 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.

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.

Do not substitute trastuzumab deruxtecan 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 the prevention of chemotherapy-induced nausea and vomiting.

HER2-Positive Early Breast Cancer

• Neoadjuvant: trastuzumab deruxtecan 5.4 mg/kg every 3 weeks for 4 cycles, followed by THP regimen for 4 cycles.

• Post Neoadjuvant: trastuzumab deruxtecan 5.4 mg/kg every 3 weeks for 14 cycles unless disease recurrence or unacceptable toxicity.

HER2-Positive, HER2-Low, or HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and HER2-Positive (IHC 3+) Solid Tumors:

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

HER2-Positive First-line Metastatic Breast Cancer:

• Trastuzumab deruxtecan 5.4 mg/kg every 3 weeks in combination with pertuzumab until disease progression or unacceptable toxicity. Cycle 1, Day 1: Trastuzumab deruxtecan 5.4 mg/kg followed by pertuzumab 840 mg. Subsequent cycles, Day 1: Trastuzumab deruxtecan 5.4 mg/kg followed by pertuzumab 420 mg.

HER2-Positive Gastric Cancer:

• 6.4 mg/kg every 3 weeks 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.
• Dose modifications should occur in renal or liver impairment.
• If you develop side effects such as interstitial lung disease (ILD), neutropenia, thrombocytopenia, or left ventricular dysfunction, your healthcare provider may temporarily stop trastuzumab deruxtecan, reduce your dose, or discontinue trastuzumab deruxtecan.

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.

Some medications interact with trastuzumab deruxtecan, 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.

Not all possible interactions are listed in this medication guide.

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 trastuzumab deruxtecan J-code when filling out forms for your treatment.

Review the trastuzumab deruxtecan PI (Package Insert) (Enhertu brand) contains more comprehensive information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Refer to the Enhertu PI and discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called the Prescribing Information (PI) or The FDA label.

• 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.

Enhertu 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.