Retevmo

Approved Uses

Retevmo is used to treat adults and children with cancers that are caused by specific changes in the RET gene. These changes are identified through a laboratory test before treatment begins. The medication is approved for the following conditions:

• Non-Small Cell Lung Cancer (NSCLC): For adults with advanced or metastatic cancer that is RET fusion-positive.
• Medullary Thyroid Cancer (MTC): For adults and children aged 2 years and older with advanced or metastatic cancer that is RET-mutant and requires treatment with a systemic medicine.
• Other Thyroid Cancers: For adults and children aged 2 years and older with advanced or metastatic RET fusion-positive thyroid cancer that has not responded to radioactive iodine treatment.
• Solid Tumors: For adults and children aged 2 years and older with advanced or metastatic solid tumors that are RET fusion-positive and have progressed during or after other treatments, or when there are no other satisfactory treatment options.

Retevmo is generally prescribed when the cancer has spread (metastatic) or is locally advanced and cannot be treated with surgery or radiation alone. It works by targeting the specific proteins produced by the abnormal RET gene to help slow or stop the growth of cancer cells.

Targeting RET Proteins

Retevmo belongs to a class of drugs known as kinase inhibitors. It is specifically designed to target and block the activity of a protein called RET (Rearranged during Transfection).

In certain types of cancer, the RET gene undergoes changes, such as mutations or fusions. These genetic alterations cause the RET protein to become overactive. When this protein is constantly active, it sends continuous signals to cells, telling them to grow, multiply, and spread uncontrollably, leading to the formation of tumors.

How Retevmo Works

Retevmo works by binding to the abnormal RET protein and blocking its signaling pathway. By inhibiting this protein, the medication can:

• Interrupt growth signals: It stops the messages that tell cancer cells to divide.
• Slow tumor progression: By cutting off these signals, the drug helps shrink tumors or prevent them from getting larger.
• Target specific cells: Because it focuses on the RET protein, it is considered a targeted therapy, though it may still affect some healthy cells in the body.

Before starting this treatment, healthcare providers typically use a laboratory test to confirm the presence of a RET gene fusion or mutation, ensuring the cancer is likely to respond to this specific mechanism.

Common Side Effects

The most frequently reported side effects of Retevmo include:

• Dry mouth
• Diarrhea or constipation
• Nausea and stomach pain
• Fatigue or tiredness
• Swelling in the hands, feet, or ankles
• High blood pressure
• Rash
• Headache
• Changes in blood tests, such as increased liver enzymes, increased cholesterol, or decreased salt (sodium) levels

Serious Side Effects

Retevmo can cause serious side effects that may require medical attention or a change in treatment. These include:

• Liver toxicity: Signs may include yellowing of the skin or eyes, dark urine, or pain in the upper right stomach area.
• Severe high blood pressure: Blood pressure should be monitored regularly during treatment.
• Heart rhythm changes: This medication can affect the electrical activity of the heart (QT prolongation), which may cause dizziness or a racing heartbeat.
• Bleeding problems: Serious and sometimes fatal bleeding can occur.
• Lung problems: Inflammation of the lungs (pneumonitis) can cause shortness of breath or cough.
• Allergic reactions: Symptoms may include fever, muscle aches, and joint pain.
• Impaired wound healing: Retevmo may affect the body's ability to heal after surgery.

Serious Risks and Monitoring

Treatment with Retevmo requires careful monitoring by a healthcare provider due to the potential for severe adverse reactions.

Liver Toxicity

Retevmo can cause hepatotoxicity (liver damage). Healthcare providers typically monitor liver function tests, including ALT and AST levels, before starting treatment and every two weeks for the first three months. Dose adjustments or treatment interruption may be necessary if liver enzymes become significantly elevated.

Lung Problems

Severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis can occur. Patients are advised to monitor for new or worsening respiratory symptoms such as cough, fever, or shortness of breath.

High Blood Pressure

Hypertension is a common side effect. Blood pressure should be controlled before starting Retevmo and monitored regularly during therapy. Some patients may require new or additional blood pressure medications.

Heart Rhythm Changes

Retevmo can cause QT interval prolongation, which affects the heart's electrical rhythm. Monitoring of heart activity (ECG) and electrolyte levels (such as potassium and magnesium) is often required, especially for those with pre-existing heart conditions or those taking other medications that affect the heart rhythm.

Bleeding Risks

Serious and sometimes fatal bleeding (hemorrhage) has occurred in patients taking this medication. Patients should seek immediate medical attention for unusual bleeding or bruising.

Other Precautions

• Hypersensitivity: Allergic-type reactions may occur, often characterized by fever, rash, and joint or muscle pain.
• Wound Healing: Retevmo may interfere with the body's ability to heal wounds. It is generally stopped for a period before and after elective surgery.
• Tumor Lysis Syndrome: This condition, caused by the rapid breakdown of cancer cells, has been reported and requires monitoring.
• Pregnancy and Reproduction: This drug can cause fetal harm. Effective contraception is recommended for females of reproductive potential and for males with female partners of reproductive potential during treatment and for a period after the final dose.

Pregnancy

Retevmo can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action and findings from animal studies, this medication may lead to birth defects or pregnancy loss. Healthcare providers typically require a pregnancy test before starting treatment for individuals who are able to become pregnant.

It is generally advised to use effective birth control during treatment and for at least one week after the final dose. This recommendation often applies to both females and males who have partners of reproductive potential.

Breastfeeding

It is not known whether Retevmo passes into breast milk or how it might affect a nursing child. Because of the potential for serious adverse reactions in an infant, breastfeeding is not recommended during treatment and for at least one week after the last dose.

Fertility

Retevmo may impair fertility in both males and females, which could affect the ability to have children. Individuals should discuss the potential impact on fertility with their healthcare provider before starting this medication.

Dosage Forms

Retevmo is supplied as a capsule for oral administration. The capsules are produced in different versions, which are distinguished by their color and the markings printed on the capsule shell.

• Oral capsule

FDA Approval Status

Retevmo (selpercatinib) was first granted accelerated approval by the FDA in May 2020. It has since received full approval for several indications involving lung and thyroid cancers, while the approval for certain solid tumors remains under the accelerated approval pathway based on clinical trial response rates.

Approved Indications

• Non-Small Cell Lung Cancer (NSCLC): Approved for adults with metastatic RET fusion-positive NSCLC.
• Medullary Thyroid Cancer (MTC): Approved for adults and pediatric patients aged 12 and older with advanced or metastatic RET-mutant MTC who require systemic therapy.
• Thyroid Cancer: Approved for adults and pediatric patients aged 12 and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and are refractory to radioactive iodine.
• Solid Tumors: Approved for adults with locally advanced or metastatic RET fusion-positive solid tumors that have progressed following prior systemic treatment or who have no satisfactory alternative treatment options.

Regulatory Requirements

The use of Retevmo requires confirmation of a RET gene alteration through an FDA-approved companion diagnostic test. There are no Boxed Warnings or Risk Evaluation and Mitigation Strategies (REMS) currently associated with this drug.

Factors Affecting Cost

The total cost of Retevmo can vary based on several factors, including your specific insurance plan, the dosage prescribed, and the pharmacy where the prescription is filled. As a specialty medication, Retevmo is typically dispensed through specialty pharmacies rather than standard retail locations.

Insurance Coverage

Insurance providers often require prior authorization before covering Retevmo. This means your healthcare provider must provide documentation to the insurance company to justify the medical necessity of the drug. Your out-of-pocket costs, such as copays or coinsurance, will depend on your plan's formulary and whether you have met your deductible.

Financial Assistance Programs

Financial support may be available to help reduce the cost of Retevmo:

• Copay Cards: Eligible patients with commercial insurance may qualify for savings on their monthly out-of-pocket costs.
• Patient Assistance Programs: Programs are often available for patients who are uninsured or underinsured and meet specific financial eligibility criteria.
• Support Services: The manufacturer provides resources through the Lilly Oncology Support Center to help patients navigate insurance and find financial aid options.