Xalkori

Approved Uses for Xalkori

Xalkori is used to treat several different types of cancer that have been identified through genetic testing as having specific abnormalities. These include:

Non-Small Cell Lung Cancer (NSCLC)

Xalkori is approved for adults with metastatic non-small cell lung cancer (cancer that has spread to other parts of the body) caused by defects in either the ALK (anaplastic lymphoma kinase) gene or the ROS1 gene.

Anaplastic Large Cell Lymphoma (ALCL)

This medication is used to treat children (1 year of age and older) and young adults with systemic anaplastic large cell lymphoma that is ALK-positive. It is typically prescribed when the lymphoma has returned (relapsed) or has not responded to other treatments (refractory).

Inflammatory Myofibroblastic Tumor (IMT)

Xalkori is used for adults and children (1 year of age and older) with ALK-positive inflammatory myofibroblastic tumors. It is used when the tumor cannot be removed by surgery (unresectable), has come back, or has not responded to other therapies.

Before starting Xalkori, a healthcare provider will perform a specific test to confirm that the tumor has the ALK or ROS1 genetic marker, as the drug is only effective in patients with these specific mutations.

Targeting Cancer Growth Signals

Xalkori belongs to a class of medications called kinase inhibitors. It works by targeting and blocking the activity of specific proteins in the body, including:

• ALK (anaplastic lymphoma kinase)
• ROS1
• c-MET (hepatocyte growth factor receptor)

In certain types of cancer, these proteins are abnormal or overactive due to genetic changes. These abnormal proteins act like a permanent "on" switch, sending constant signals that tell cancer cells to divide, grow, and spread throughout the body.

How the Medication Works

Xalkori is designed to bind to these specific proteins and interfere with their signaling pathways. By blocking these signals, the medication can:

• Slow down or stop the growth of the tumor.
• Cause cancer cells to die.
• Prevent the cancer from spreading to other parts of the body.

Because Xalkori targets specific proteins found mainly on cancer cells, it is considered a targeted therapy. Before starting treatment, doctors perform specialized tests to confirm that the tumor has the specific genetic markers, such as ALK or ROS1, that Xalkori is designed to treat.

Common Side Effects

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

• Vision changes: Blurred vision, seeing flashes of light, double vision, or new floaters. These symptoms often occur within the first few weeks of treatment.
• Digestive problems: Nausea, vomiting, diarrhea, constipation, and decreased appetite.
• Swelling: Fluid retention in the hands, feet, or legs (edema).
• General symptoms: Fatigue, dizziness, and changes in the sense of taste.
• Nerve issues: Numbness, tingling, or a "pins and needles" sensation in the hands or feet.
• Infections: Increased risk of upper respiratory infections.

Serious Side Effects

While less common, some side effects can be severe and require immediate medical attention. Contact a healthcare provider right away if you experience:

• Liver problems: Yellowing of the skin or the whites of the eyes (jaundice), dark urine, extreme tiredness, or pain on the right side of the stomach area.
• Lung problems: New or worsening trouble breathing, shortness of breath, cough, or fever. These may be signs of lung inflammation.
• Heart rhythm changes: Feeling lightheaded, faint, or having a very slow or irregular heartbeat.
• Severe vision loss: Any sudden or significant change in vision should be reported immediately to a doctor.

Liver Toxicity

Severe, life-threatening, or fatal liver damage has occurred in patients taking Xalkori. Healthcare providers typically perform liver function tests every two weeks for the first two months of treatment and then once a month thereafter. Treatment may be interrupted, reduced, or permanently stopped if liver enzymes become significantly elevated.

Lung Inflammation

Xalkori can cause severe or fatal interstitial lung disease (ILD) or pneumonitis. Patients are monitored for pulmonary symptoms such as cough, fever, or shortness of breath. If these symptoms occur and are determined to be related to the medication, treatment is usually discontinued permanently.

Heart Rhythm and Rate Changes

• QT Interval Prolongation: This medication can affect the heart's electrical rhythm, which may lead to serious heart palpitations. Monitoring often includes regular electrocardiograms (ECGs) and electrolyte blood tests.
• Bradycardia: A slow heart rate (bradycardia) has been reported. Healthcare providers monitor heart rate and blood pressure regularly, especially in patients who are also taking other medications that can slow the heart rate.

Vision Disorders

Vision changes are common and may include light flashes, blurred vision, or sensitivity to light. While these are often mild, severe vision loss has been reported. An eye examination is typically recommended if new or worsening vision symptoms develop.

Embryo-Fetal Toxicity

Xalkori can cause harm to a fetus when administered to a pregnant woman. Females of reproductive potential and males with female partners of reproductive potential should use effective contraception during treatment and for several months after the final dose. Breastfeeding is not recommended during treatment.

Kidney Function

Dose adjustments may be necessary for patients with severe kidney impairment. Healthcare providers evaluate kidney function before and during treatment to determine the appropriate dosage.

Pregnancy

Xalkori may cause fetal harm when administered to a pregnant woman. Before starting treatment, healthcare providers typically perform a pregnancy test for individuals who can become pregnant to ensure they are not pregnant.

Because of the risks to a developing baby, the following precautions are usually recommended:

• Contraception for women: Use effective birth control during treatment and for at least 4 months after the final dose.
• Contraception for men: Use condoms during treatment and for at least 4 months after the final dose when with a partner who can become pregnant.

If you become pregnant or think you might be pregnant while taking this medication, notify your healthcare provider immediately.

Breastfeeding

It is not known if Xalkori passes into breast milk. Because of the potential for serious adverse reactions in a nursing child, it is recommended that individuals do not breastfeed while taking this medication and for 45 days after the last dose. Patients should discuss the best way to feed their baby with a healthcare professional during this time.

Dosage Forms

Xalkori is available in two oral formulations:

• Capsules: These are intended to be swallowed whole.
• Oral Pellets: These are provided in a capsule that must be opened. The pellets are then sprinkled on soft food or mixed with a liquid for administration.

The medication is available in various strengths to accommodate different dosing requirements for adults and children.

FDA Approval History

Xalkori was first granted accelerated approval by the U.S. Food and Drug Administration (FDA) in 2011. Since its initial release, the FDA has expanded its approved uses to include several different types of cancer characterized by specific genetic alterations.

Approved Indications

The FDA has approved Xalkori for the following uses:

• Non-Small Cell Lung Cancer (NSCLC): For adults with metastatic NSCLC whose tumors are positive for the ALK (anaplastic lymphoma kinase) or ROS1 gene.
• Anaplastic Large Cell Lymphoma (ALCL): For pediatric patients (1 year and older) and young adults with ALK-positive systemic ALCL that has returned or did not respond to other treatments.
• Inflammatory Myofibroblastic Tumor (IMT): For adults and pediatric patients (1 year and older) with ALK-positive IMT that cannot be removed by surgery, has returned, or did not respond to other treatments.

Regulatory Requirements

Xalkori is a prescription medication. Before starting treatment, the FDA requires healthcare providers to confirm the presence of the ALK or ROS1 biomarkers using an FDA-approved diagnostic test. This ensures the medication is targeted to patients with the specific genetic profiles that the drug is designed to treat.

Safety Monitoring

While Xalkori does not currently have a boxed warning, the FDA monitors its safety profile for serious risks. These include potential liver toxicity, interstitial lung disease (lung inflammation), heart rhythm changes (QT prolongation), and vision loss. Healthcare providers are advised to monitor patients regularly for these conditions during treatment.

FDA Approval History

Xalkori (crizotinib) first received FDA approval in August 2011. It was initially approved under the agency's accelerated approval program, which allows for earlier access to drugs that treat serious conditions based on promising clinical trial data. Since then, the FDA has expanded its approved uses to include several different conditions characterized by specific genetic mutations.

Approved Indications

• Non-Small Cell Lung Cancer (NSCLC): Xalkori is approved for adults with metastatic NSCLC whose tumors are positive for the anaplastic lymphoma kinase (ALK) or ROS1 gene.
• Anaplastic Large Cell Lymphoma (ALCL): In 2021, the FDA approved Xalkori for pediatric patients 1 year of age and older and young adults with ALK-positive ALCL that has returned or did not respond to previous treatments.
• Inflammatory Myofibroblastic Tumor (IMT): In 2022, the FDA approved the medication for adult and pediatric patients 1 year of age and older with ALK-positive IMT that is unresectable, recurrent, or refractory.

The FDA requires specific diagnostic tests to confirm the presence of ALK or ROS1 mutations before treatment begins, as the drug is only effective in patients with these specific genetic markers.