Nerlynx

Early-Stage Breast Cancer

Nerlynx is used for the extended adjuvant treatment of early-stage breast cancer that is HER2-positive. In this context, extended adjuvant treatment means the medication is started after a patient has already completed a primary course of therapy involving the drug trastuzumab. The purpose of using Nerlynx in this situation is to further reduce the risk of the cancer coming back.

Advanced or Metastatic Breast Cancer

This medication is also approved for use in adults with HER2-positive breast cancer that is advanced or has spread to other parts of the body (metastatic). When used for advanced disease, Nerlynx is prescribed in combination with another chemotherapy medication called capecitabine. This combination is typically used for patients who have already received two or more other types of anti-HER2 treatments for their metastatic disease.

Targeting Cancer Growth

Nerlynx is a type of targeted therapy called a kinase inhibitor. It works by interfering with specific proteins that promote the growth of cancer cells. In many breast cancers, a protein called human epidermal growth factor receptor 2 (HER2) is found in high amounts on the surface of the cells.

When HER2 proteins are active, they send signals to the inside of the cell telling it to grow and divide. Nerlynx works by binding permanently to HER2, as well as related proteins known as HER1 and HER4. This binding blocks the signaling process.

By shutting down these growth signals, Nerlynx helps to:

• Prevent cancer cells from multiplying.
• Reduce the likelihood of the cancer coming back after surgery and other treatments.

Common Side Effects

The most frequent side effect of Nerlynx is diarrhea, which can be severe. Other common side effects include:

• Nausea and vomiting
• Stomach-area pain or bloating
• Tiredness or weakness
• Mouth sores
• Skin rash or dry skin
• Muscle spasms
• Loss of appetite
• Nail changes, such as color changes or brittleness
• Indigestion
• Nosebleeds
• Urinary tract infections

Serious Side Effects

While less common, some side effects can be severe and require immediate medical attention:

• Severe Diarrhea: This can lead to significant fluid loss (dehydration) and kidney problems.
• Liver Problems: Symptoms may include yellowing of the skin or the whites of the eyes (jaundice), dark-colored urine, or pain in the upper right side of the stomach area.
• Allergic Reactions: Signs may include hives, difficulty breathing, or swelling of the face, lips, tongue, or throat.

Severe Diarrhea

Severe diarrhea is a significant risk with this medication and can lead to dehydration or kidney injury. Prophylactic anti-diarrheal treatment is typically started with the first dose of Nerlynx to manage this risk. If diarrhea occurs despite preventative measures, dose adjustments or treatment interruption may be necessary.

Liver Toxicity

Changes in liver function tests have been observed in patients taking Nerlynx. Monitoring through regular blood tests is required to check for liver injury. Symptoms such as unusual tiredness, nausea, vomiting, or yellowing of the skin and eyes should be reported to a healthcare provider immediately.

Embryo-Fetal Toxicity

Nerlynx can cause harm to a developing fetus. Individuals of reproductive potential are advised to use effective contraception during treatment and for one month after the final dose. Breastfeeding is also discouraged during this period.

Medication Interactions

Certain drugs can affect the absorption or metabolism of Nerlynx. This includes stomach acid reducers like proton pump inhibitors, which should be avoided. Other medications, such as antacids or H2-receptor antagonists, may require specific dosing schedules to avoid interactions.

Pregnancy

Nerlynx can cause harm to a developing fetus if taken during pregnancy. Animal studies have indicated that the medication may lead to fetal death or birth defects. Because of these risks, healthcare providers advise against using this medication while pregnant.

Patients of reproductive potential should consider the following precautions:

• Pregnancy Testing: Healthcare providers typically verify a negative pregnancy status before starting treatment.
• Contraception for Females: Effective birth control should be used during treatment and for at least 1 month after the final dose.
• Contraception for Males: Men with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the final dose.

Breastfeeding

It is not known if neratinib, the active ingredient in Nerlynx, passes into human breast milk. Because of the potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended during treatment and for at least 1 month after the last dose.

Dosage Forms

Nerlynx is supplied as an oral medication in the following form:

• Oral Tablet: These are film-coated tablets designed to be taken by mouth.

The tablets should be kept in their original packaging to protect them from moisture and stored at room temperature.

FDA Approval Status

The U.S. Food and Drug Administration (FDA) first approved Nerlynx in July 2017. It was initially indicated for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy.

In February 2020, the FDA expanded the approved use of Nerlynx to include treatment in combination with capecitabine for adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens.

Safety Notifications

The FDA-approved labeling includes significant warnings regarding severe diarrhea and hepatotoxicity (liver toxicity). While there is no Boxed Warning or Risk Evaluation and Mitigation Strategy (REMS) required, clinical management typically involves prophylactic antidiarrheal medication starting with the first dose of Nerlynx to manage potential gastrointestinal side effects. Liver function monitoring is also required during treatment.

Cost Factors

The price of Nerlynx can vary significantly based on several factors. Because it is a specialty medication, it is usually not available at standard retail pharmacies and must be obtained through a specialty pharmacy. Your out-of-pocket expenses will depend on your specific insurance plan's formulary and your remaining deductible.

Insurance and Financial Assistance

• Insurance Coverage: Most commercial insurance plans, Medicare Part D, and Medicaid provide coverage for Nerlynx. However, the copayment or coinsurance amounts can vary widely between plans.
• Manufacturer Support: The manufacturer may offer a copay savings card for patients with commercial insurance to help reduce out-of-pocket costs.
• Patient Assistance Programs: For individuals who are uninsured or underinsured, there may be patient assistance programs available that provide the medication at a lower cost or for free, depending on financial eligibility.

Generic Availability

Nerlynx is currently only available as a brand-name medication. There is no generic version of neratinib available at this time, which generally results in a higher cost than if a generic alternative were on the market.