Enhertu

Approved Indications

Enhertu is a targeted medication used to treat several types of cancer that produce a protein called human epidermal growth factor receptor 2 (HER2). It is generally used for cancers that are unresectable (cannot be removed by surgery) or metastatic (have spread to other parts of the body).

Breast Cancer

• HER2-positive breast cancer: For adults who have already received a prior anti-HER2-based treatment regimen.
• HER2-low breast cancer: For adults who have received prior chemotherapy for metastatic disease or whose cancer returned during or shortly after completing chemotherapy.

Stomach Cancer

Enhertu is used to treat HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma in adults who have previously received a treatment containing trastuzumab.

Lung Cancer

It is used for adults with metastatic non-small cell lung cancer (NSCLC) whose tumors have specific HER2 mutations and who have already received prior systemic therapy.

Solid Tumors

This medication may also be used for adults with HER2-positive solid tumors that have spread or cannot be removed, particularly when no other satisfactory treatment options are available.

Targeted Delivery System

Enhertu is designed as an antibody-drug conjugate (ADC). This type of medication works by combining a targeted antibody with a potent chemotherapy drug. It specifically targets cells that have a protein called human epidermal growth factor receptor 2 (HER2) on their surface.

How the Medication Works

The process of how Enhertu works in the body involves several steps:

• Targeting: The antibody portion of the drug (trastuzumab) circulates through the bloodstream and attaches to HER2 receptors on the surface of cancer cells.
• Internalization: Once attached, the cancer cell pulls the entire medication inside itself.
• Release: Inside the cell, enzymes break the linker that holds the antibody and chemotherapy together. This releases the chemotherapy drug (deruxtecan) directly into the cell.
• Cell Death: The chemotherapy blocks an enzyme called topoisomerase I, which cancer cells need to repair their DNA. This damage prevents the cell from multiplying and eventually causes it to die.

The Bystander Effect

Enhertu is unique because the chemotherapy component can pass through the cell membrane of the initial target cell. This allows it to reach and kill neighboring cancer cells, even if those nearby cells have lower levels of the HER2 protein. This process is often referred to as the bystander effect.

Common Side Effects

Many people taking Enhertu experience mild to moderate side effects. These may include:

• Nausea and vomiting
• Fatigue or weakness
• Hair loss (alopecia)
• Constipation or diarrhea
• Decreased appetite
• Muscle, bone, or joint pain
• Headache
• Cough
• Low red blood cell counts (anemia) or white blood cell counts (neutropenia)

Serious Side Effects

Some side effects can be severe or life-threatening and require immediate medical attention. These include:

• Lung Problems: Enhertu can cause inflammation of the lungs, known as interstitial lung disease or pneumonitis. Symptoms to watch for include new or worsening shortness of breath, cough, or fever.
• Heart Problems: This medication may affect how well the heart pumps blood (left ventricular dysfunction). Signs of heart issues can include swelling in the ankles or legs, shortness of breath, or palpitations.
• Severe Low White Blood Cell Counts: A significant drop in white blood cells can increase the risk of developing serious or even fatal infections.
• Infusion-Related Reactions: Some patients may experience a reaction while receiving the medication, which may involve fever, chills, or breathing difficulties.

Boxed Warnings

Enhertu has boxed warnings for the following serious conditions:

• Interstitial Lung Disease (ILD) and Pneumonitis: This medication can cause severe, life-threatening, or fatal lung inflammation. Healthcare providers monitor for new or worsening respiratory symptoms such as cough, fever, or shortness of breath. Treatment may need to be delayed, dose-reduced, or permanently discontinued if lung problems are suspected or confirmed.
• Embryo-Fetal Toxicity: Exposure to this drug during pregnancy can cause birth defects or death to an unborn baby. Females of reproductive potential are advised to use effective contraception during treatment and for seven months after the final dose. Male patients with female partners of reproductive potential should use effective contraception for four months after the last dose.

Additional Precautions

Other significant precautions include:

• Neutropenia: A decrease in white blood cell counts (neutropenia) can occur, which may increase the risk of serious infections. Healthcare providers typically monitor complete blood counts before starting treatment and prior to each dose.
• Left Ventricular Dysfunction: This treatment may weaken the heart muscle's ability to pump blood, potentially leading to heart failure. Heart function, specifically the left ventricular ejection fraction (LVEF), is usually assessed before starting therapy and at regular intervals during treatment.

Pregnancy

Enhertu can cause fetal harm when administered to a pregnant woman. Healthcare providers typically perform a pregnancy test to ensure a patient is not pregnant before starting treatment. If this medication is used during pregnancy, or if a patient becomes pregnant while taking it, there is a risk of serious injury or death to the developing fetus.

Individuals who can become pregnant should use effective contraception during treatment and for at least 7 months after the final dose. Males with female partners of reproductive potential should use effective contraception during treatment and for at least 4 months after the last dose.

Breastfeeding

It is not known whether Enhertu 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 at least 7 months after the final dose.

Fertility

Enhertu may impair fertility in males. Individuals concerned about their ability to have children in the future should discuss these risks with their healthcare provider before starting treatment.

Available Forms

Enhertu is available as a lyophilized powder for injection. It is provided in a single-dose vial and does not contain any preservatives.

Administration

A healthcare provider must reconstitute the powder and dilute it into an infusion bag before it is given to the patient. The medication is administered as an intravenous infusion.

FDA Approval Status

Enhertu (fam-trastuzumab deruxtecan-nxki) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of several advanced or metastatic cancers. It is primarily used for patients who have already received prior treatments. Approved indications include:

• Breast Cancer: Used for HER2-positive or HER2-low breast cancer that cannot be removed by surgery or has spread to other parts of the body.
• Stomach Cancer: Used for HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
• Lung Cancer: Used for metastatic non-small cell lung cancer (NSCLC) that carries specific HER2 mutations.

Boxed Warnings

The FDA has required a boxed warning for Enhertu, which is the most serious type of warning for a prescription medication. These warnings cover:

• Interstitial Lung Disease (ILD) and Pneumonitis: Enhertu can cause severe, life-threatening, or fatal lung inflammation. Patients must be monitored closely for symptoms such as cough, fever, or shortness of breath. If these symptoms occur, treatment may need to be interrupted or permanently stopped.
• Embryo-Fetal Toxicity: This medication can cause significant harm or death to an unborn baby. Healthcare providers require pregnancy testing for females of reproductive potential before starting treatment. Effective birth control must be used during treatment and for a specified period after the final dose.

Administration and Safety Monitoring

Enhertu is administered as an intravenous (IV) infusion by a healthcare professional. Because of its potential for serious side effects, regulatory guidelines require ongoing monitoring of heart function (left ventricular ejection fraction) and respiratory health throughout the course of treatment. It is not recommended for use during pregnancy or while breastfeeding.

Factors Affecting Price

The total price of Enhertu treatment depends on several variables. Because it is a specialty medication administered in a clinical setting, costs often include more than just the drug itself.

• Insurance Coverage: Out-of-pocket costs depend on whether the drug is covered under a medical or pharmacy benefit and the specific terms of the insurance plan.
• Treatment Plan: The dosage is calculated based on the patient's weight, and the frequency of infusions affects the overall cost over time.
• Clinical Fees: Costs associated with the healthcare facility, nursing staff, and equipment needed for the intravenous infusion are typically billed alongside the medication.

Biosimilar Status

Enhertu is a biologic drug, and there are currently no biosimilar versions available. Biosimilars are similar to generic versions of traditional drugs and often cost less than the original brand-name product.

Financial Support Programs

Financial assistance may be available through the drug manufacturer for patients who meet certain eligibility requirements. These programs can include co-pay assistance for those with commercial insurance or patient assistance programs for individuals without adequate coverage.