trastuzumab deruxtecan

Breast Cancer

Trastuzumab deruxtecan is used to treat adults with breast cancer that is unresectable (cannot be removed by surgery) or metastatic (has spread to other parts of the body). It is used in the following situations:

• HER2-positive breast cancer: For patients who have already received a prior treatment regimen specifically targeting the HER2 protein.
• HER2-low breast cancer: For patients who have received prior chemotherapy for metastatic disease or whose cancer returned within six months of completing chemotherapy after surgery.

Stomach Cancer

This medication is used for adults with HER2-positive gastric (stomach) or gastroesophageal junction (GEJ) adenocarcinoma that is locally advanced or has spread. It is typically used after the patient has already received a previous treatment containing trastuzumab.

Lung Cancer

Trastuzumab deruxtecan is used to treat adults with metastatic non-small cell lung cancer (NSCLC) whose tumors have specific HER2 mutations. It is intended for patients who have already tried at least one other systemic therapy.

Other HER2-Positive Solid Tumors

This medication is also used for adults with various other types of HER2-positive solid tumors that are unresectable or metastatic. It is generally used when the cancer has progressed following prior treatment and there are no other satisfactory alternative treatment options available.

Mechanism of Action

Trastuzumab deruxtecan belongs to a class of medications known as antibody-drug conjugates (ADCs). It is designed to deliver a potent chemotherapy drug directly to cancer cells while limiting exposure to healthy cells.

Targeting HER2 Proteins

The medication consists of two main parts linked together: a monoclonal antibody and a chemotherapy drug. The antibody part is designed to find and attach to human epidermal growth factor receptor 2 (HER2), a protein found on the surface of many types of cancer cells. The antibody acts as a homing device to locate these specific cells.

Internalization and Release

Once the medication attaches to the HER2 protein on a cancer cell, the entire complex is taken inside the cell. After it is inside, enzymes break the link between the antibody and the chemotherapy drug (deruxtecan), releasing the chemotherapy to do its work.

Cell Death and the Bystander Effect

The released chemotherapy works by blocking an enzyme called topoisomerase I, which cells need to repair and copy their DNA. When this enzyme is blocked, the cancer cell cannot multiply and eventually dies. Because the chemotherapy part of this medication can pass through cell membranes, it may also move into and kill neighboring cancer cells, a process sometimes called the bystander effect.

Common Side Effects

Many people receiving this medication experience side effects. Common symptoms include:

• Nausea and vomiting
• Fatigue or weakness
• Hair loss
• Constipation or diarrhea
• Decreased appetite
• Muscle, bone, or joint pain
• Headache
• Cough
• Stomach pain

Serious Side Effects

Some side effects can be severe or life-threatening. Seek medical attention immediately for:

• Lung Problems: New or worsening shortness of breath, cough, or fever. These may be signs of interstitial lung disease or pneumonitis.
• Low Blood Cell Counts: Signs of infection such as fever and chills, or signs of low platelets like unusual bruising or bleeding.
• Heart Issues: Shortness of breath, swelling in the ankles or legs, or a racing heartbeat.
• Infusion Reactions: Fever, chills, or dizziness occurring during or shortly after the injection.

Your healthcare provider will monitor your blood counts and heart function regularly during treatment to check for these issues.

Boxed Warnings

Interstitial Lung Disease (ILD) and Pneumonitis: This medication can cause severe, life-threatening, or fatal lung inflammation. Patients are monitored for new or worsening respiratory symptoms such as cough, shortness of breath, or fever. Depending on the severity, treatment may be delayed, the dose reduced, or the medication permanently discontinued.

Embryo-Fetal Toxicity: This drug can cause fetal harm when administered to a pregnant woman. Females of reproductive potential must have a pregnancy test before starting treatment and use effective contraception during and after therapy.

Additional Precautions

Neutropenia

Severe decreases in white blood cell counts, known as neutropenia, can occur. This condition can lead to serious infections. Healthcare providers monitor complete blood counts before each dose and as clinically indicated.

Left Ventricular Dysfunction

Treatment may lead to a decrease in the heart's ability to pump blood (left ventricular ejection fraction). Heart function is assessed before starting treatment and at regular intervals during therapy. Treatment may be interrupted if the heart's pumping ability decreases significantly.

Reproductive Health

• Females: Effective contraception is required during treatment and for 7 months after the last dose.
• Males: Men with female partners of reproductive potential should use effective contraception during treatment and for 4 months after the last dose.
• Breastfeeding: It is advised not to breastfeed during treatment and for 7 months after the final dose due to the risk of serious side effects in the infant.

Pregnancy Risks

Trastuzumab deruxtecan can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action, exposure to this medication during pregnancy may lead to low levels of amniotic fluid. This condition can cause serious problems for the fetus, including underdeveloped lungs, skeletal abnormalities, and death.

Individuals who can become pregnant should have a pregnancy test to confirm they are not pregnant before starting treatment. It is important to discuss the potential risks to a fetus with a healthcare provider if pregnancy occurs or is planned during treatment.

Contraception Requirements

• Females: Use effective contraception during treatment and for at least 7 months after the final dose.
• Males: Those with female partners who can become pregnant should use effective contraception during treatment and for at least 4 months after the final dose.

Breastfeeding

It is not known if trastuzumab deruxtecan passes into human breast milk. Because of the potential for serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment and for 7 months after the last dose.

Dosage Forms

Trastuzumab deruxtecan is supplied as a sterile, preservative-free powder in a single-dose vial. The powder is typically described as a white to yellowish-white cake.

Administration

This medication is intended for intravenous use only. Before administration, a healthcare provider must reconstitute the powder and further dilute it into an infusion bag. It is not available in oral forms, such as tablets or capsules, and cannot be self-administered.

FDA Approval Status

Trastuzumab deruxtecan (fam-trastuzumab deruxtecan-nxki) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of several advanced or metastatic cancers. These approvals are generally based on the presence of the HER2 protein or specific HER2 mutations. Approved indications include:

• Breast Cancer: Used for HER2-positive metastatic breast cancer, as well as HER2-low and HER2-ultralow metastatic breast cancer in patients who have received prior systemic treatments.
• Gastric Cancer: Used for HER2-positive locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma.
• Lung Cancer: Used for metastatic non-small cell lung cancer (NSCLC) with specific HER2 mutations.
• Solid Tumors: Used for adult patients with unresectable or metastatic HER2-positive solid tumors who have received prior treatment and have no satisfactory alternative treatment options.

Boxed Warnings

The FDA-approved labeling for trastuzumab deruxtecan includes a Boxed Warning, the most serious type of warning, for the following risks:

• Interstitial Lung Disease (ILD) and Pneumonitis: This medication can cause severe, life-threatening, or fatal lung inflammation. Patients must be monitored for new or worsening respiratory symptoms such as cough, fever, or shortness of breath.
• Embryo-Fetal Toxicity: Exposure to this drug during pregnancy can cause harm to a developing fetus. Effective contraception is required for patients of reproductive potential during treatment and for a specified period after the final dose.

Regulatory History

Trastuzumab deruxtecan received its initial accelerated approval from the FDA in December 2019. Since then, its approved uses have expanded significantly to include a broader range of HER2-expressing tumors across different organs, based on clinical trial data demonstrating its efficacy in these populations.

Factors Affecting Cost

Trastuzumab deruxtecan is a specialty medication that is supplied in 100 mg single-dose vials. Because the dosage is calculated based on a patient's body weight, the amount of medication needed—and the resulting cost—will vary from person to person. Additionally, since the drug must be administered as an intravenous infusion by a healthcare professional, total costs typically include both the price of the medication and facility fees for the clinical service.

Insurance and Prior Authorization

Most insurance plans cover trastuzumab deruxtecan for its FDA-approved uses, though many require prior authorization. This process involves your healthcare provider submitting documentation to your insurance company to prove the medical necessity of the treatment before they agree to cover the cost. Patients may still be responsible for out-of-pocket expenses, such as deductibles, co-pays, or co-insurance.

Financial Assistance Programs

Financial assistance may be available for patients who have difficulty affording their treatment. The manufacturer often provides patient support programs, which may include:

• Co-pay assistance: For eligible patients with commercial insurance to help lower out-of-pocket costs.
• Patient assistance programs: For patients who are uninsured or underinsured and meet specific financial criteria.
• Support services: Resources to help patients and providers navigate insurance coverage and reimbursement processes.

It is recommended to speak with a hospital financial counselor or a specialty pharmacy to get a detailed estimate of costs based on your specific insurance plan and treatment schedule.