Alectinib

Approved Uses

Alectinib is used to treat adults with non-small cell lung cancer (NSCLC) that is caused by an abnormal anaplastic lymphoma kinase (ALK) gene. It is prescribed in the following clinical situations:

• Metastatic Cancer: It is used to treat ALK-positive NSCLC that has spread to other parts of the body (metastatic). It may be used as a first-line treatment for this condition.
• Adjuvant Treatment: It is used as a follow-up treatment after the surgical removal of a tumor in patients with ALK-positive NSCLC. This use is specifically for patients whose tumors are at least 4 centimeters or whose cancer has spread to the lymph nodes.

Before starting treatment, a healthcare provider must confirm that the patient's cancer is ALK-positive using a specific, FDA-approved diagnostic test. Alectinib belongs to a class of medications called kinase inhibitors, which work by blocking the action of the abnormal protein that signals cancer cells to multiply.

Mechanism of Action

Alectinib belongs to a class of drugs known as kinase inhibitors. It is designed to target a specific protein called anaplastic lymphoma kinase (ALK), which is found on the surface of some cancer cells.

In people with ALK-positive non-small cell lung cancer, the ALK gene is altered. This genetic change causes the body to produce an abnormal ALK protein that stays permanently switched on. This overactive protein sends constant signals to cancer cells, telling them to divide and spread rapidly.

Alectinib works by attaching itself to the abnormal ALK protein and blocking its activity. By interrupting these signals, the medication helps to:

• Slow or stop the growth of cancer cells.
• Prevent the cancer from spreading to other parts of the body.
• Shrink tumors in patients where the cancer has already spread.

Because alectinib is able to cross the blood-brain barrier, it is also effective at reaching and treating cancer cells that have moved into the brain or central nervous system.

Common Side Effects

• Constipation
• Feeling tired or weak
• Swelling in the hands, feet, or around the eyes
• Muscle pain, tenderness, or aching
• Cough
• Rash
• Nausea or diarrhea
• Headache
• Anemia (low red blood cell count)

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

• Liver problems: Yellowing of the skin or eyes (jaundice), dark urine, itchy skin, or pain in the upper right stomach area.
• Lung problems: New or worsening shortness of breath, cough, or fever.
• Heart rhythm changes: A very slow heartbeat, dizziness, or feeling lightheaded.
• Severe muscle damage: Unexplained or persistent muscle pain, tenderness, or weakness.
• Kidney problems: Changes in the frequency, color, or amount of urine.

Alectinib can make your skin more sensitive to sunlight. It is important to avoid prolonged sun exposure and use sun protection, such as sunscreen and protective clothing, while taking this medicine and for at least seven days after your final dose.

Liver Toxicity

Alectinib can cause serious liver damage. Healthcare providers typically monitor liver function through blood tests every two weeks for the first three months of treatment, and then once a month or as needed. Treatment may be interrupted, reduced, or stopped if liver enzyme levels become too high.

Lung Problems

Severe or life-threatening inflammation of the lungs, known as interstitial lung disease or pneumonitis, has occurred in patients taking this medication. New or worsening respiratory symptoms, such as shortness of breath, cough, or fever, are usually evaluated immediately.

Heart Rate and Blood Pressure

This medication may cause a slow heart rate (bradycardia). Monitoring of heart rate and blood pressure is often performed during treatment. In some cases, other medications that slow the heart rate may need to be adjusted or stopped to manage this risk.

Muscle and Kidney Issues

• Muscle Pain: Elevated levels of creatine phosphokinase (CPK), an enzyme released when muscles are damaged, can occur. Muscle pain, tenderness, and weakness are monitored during therapy.
• Kidney Impairment: Severe kidney problems have been reported. Healthcare providers may monitor kidney function throughout the course of treatment.

Hemolytic Anemia

Alectinib can cause hemolytic anemia, a condition where red blood cells are destroyed faster than the body can replace them. Blood counts are typically monitored to check for signs of this condition, such as fatigue or yellowing of the skin.

Sun Sensitivity

Increased sensitivity to sunlight (photosensitivity) is common. It is generally advised to avoid prolonged sun exposure and use protective clothing and broad-spectrum sunscreen while taking this drug and for seven days after the final dose.

Pregnancy and Reproduction

Alectinib can cause fetal harm when administered to a pregnant woman. Females of reproductive potential are advised to use effective contraception during treatment and for one week after the final dose. Males with female partners of reproductive potential should use effective contraception during treatment and for three months after the final dose.

Pregnancy Considerations

Alectinib can cause fetal harm when administered to a pregnant woman. Based on animal studies and its mechanism of action, the medication may lead to birth defects or pregnancy loss. There are no well-controlled studies regarding its use in pregnant humans.

Healthcare providers typically advise the following regarding contraception:

• Females: Those who can become pregnant should use effective birth control during treatment and for at least 1 week after the final dose.
• Males: Men with female partners of reproductive potential should use effective birth control during treatment and for at least 3 months after the final dose.

Breastfeeding Considerations

It is not known whether alectinib passes into human breast milk. Due to the risk of serious side effects in a nursing infant, breastfeeding is not recommended during treatment. Patients are generally advised to wait at least 1 week after their last dose before starting or resuming breastfeeding.

Dosage Forms

Alectinib is available as a capsule for oral administration. It is intended to be swallowed whole and should be taken with food.

• Oral capsule

FDA Approval History

Alectinib was first granted accelerated approval by the U.S. Food and Drug Administration (FDA) in 2015 for patients with metastatic ALK-positive non-small cell lung cancer (NSCLC) who could no longer tolerate or whose cancer progressed on crizotinib. It received full approval for the first-line treatment of metastatic ALK-positive NSCLC in 2017.

Recent Indications

In April 2024, the FDA expanded the approval of alectinib to include adjuvant treatment. This means it can be used after surgery to remove the tumor in patients with ALK-positive NSCLC whose tumors are at least 4 cm or are node-positive.

Diagnostic Requirements

The FDA requires the use of an FDA-approved test to confirm the presence of an anaplastic lymphoma kinase (ALK) mutation before starting treatment. This ensures the medication is used only in patients whose cancer is likely to respond to the drug.

Safety Oversight

There are currently no Boxed Warnings or Risk Evaluation and Mitigation Strategies (REMS) required by the FDA for this medication. However, it remains under standard post-marketing surveillance to monitor long-term safety and efficacy.

Insurance and Out-of-Pocket Costs

The price of alectinib is largely determined by your health insurance plan. While most plans provide coverage for this medication, patients may still be responsible for significant out-of-pocket expenses, such as deductibles, copayments, or coinsurance. It is recommended to contact your insurance provider to understand the specific costs associated with your plan.

Financial Assistance Programs

Because this medication can be expensive, financial assistance may be available for eligible patients. Some individuals may qualify for programs offered by the manufacturer or independent charitable foundations that help cover the cost of treatment. Co-pay savings cards may also be available for those with commercial insurance to help reduce monthly expenses.

Pharmacy Requirements

Alectinib is typically dispensed through specialty pharmacies rather than standard retail pharmacies. Specialty pharmacies focus on medications for complex conditions and often provide additional services, such as help with insurance authorizations and identifying financial aid resources.

Generic Availability

Alectinib is currently available only as a brand-name medication. There are no generic versions available at this time, which generally results in a higher cost compared to medications that have generic alternatives.