Capmatinib: Uses, Dose, Side Effects, and Mechanism

What Is the Use of Capmatinib?

Capmatinib is an anticancer drug used to treat metastatic non-small cell lung cancer (NSCLC) in adults with a genetic change called MET exon 14 skipping mutation. It is a targeted therapy drug approved by the United States Food and Drug Administration (U.S. FDA) on June 20, 2020, to treat patients with advanced NSCLC whose cancer has spread to other parts of the body.

Capmatinib is classified as a tyrosine kinase inhibitor (TKI). Tyrosine kinase inhibitors are cancer treatment drugs that block cancer cell growth and spread by inhibiting specific enzymes.

Capmatinib targets the MET receptor, which is a protein found on cancer cells. The MET receptor is abnormally activated in non-small cell lung cancer and can cause cancer cells to multiply and spread to other parts of the body.

Recent clinical and real-world evidence have demonstrated that capmatinib can significantly improve tumor response and control in patients with MET exon 14-mutated NSCLC, including those with brain metastases. Care should be taken during treatment, as Capmatinib can cause side effects, including lung inflammation (pneumonitis), increased liver enzyme levels, and photosensitivity.

How Does the Capmatinib Drug Work?

Capmatinib inhibits the enzyme tyrosine kinase by restricting the proto-oncogene c-MET (Mesenchymal epithelial transition) or HGFR (Hepatocyte growth factor receptor). Overexpression and mutation of c-MET, a tyrosine kinase receptor, can drive the growth, proliferation, and spread of tumor cells throughout the body. Capmatinib inhibits phosphorylation by specifically binding to the c-MET (mesenchymal-epithelial transition) proto-oncogene, disrupting signal transduction and leading to the death of tumor cells that overexpress c-MET.

For Patients

When and Why Is Capmatinib Prescribed?

Doctors prescribe Capmatinib for adult patients with metastatic NSCLC after establishing that there is a MET exon 14 skipping mutation in the patient’s sample using molecular testing.

It is generally used in cases where:

• The lung cancer has spread to other body parts.
• Genetic testing has confirmed a change in the MET gene.
• Targeted therapy is appropriate for use in place of conventional chemotherapy.

This ensures that the treatment targets the specific cause of lung cancer in a personalized way.

Recommended Dose of Capmatinib

Capmatinib is provided in two strengths: 150 mg and 200 mg oral tablets.

The recommended dose is 400 mg twice daily (two 200 mg tablets per dose). The doctor may decide to reduce the dose in cases of side effects:

• 300 mg twice daily (two 150 mg tablets per dose).
• 200 mg twice daily in cases of further dose reduction.

Administration of Capmatinib

• The tablets should be taken with or without food.
• The tablets should be taken whole and not crushed or chewed.
• The tablets should be taken at regular intervals as prescribed by a doctor.

How Effective Is Capmatinib Against Non-small Cell Lung Carcinoma?

The drug Capmatinib has been proven effective in adult patients with metastasis of small lung carcinoma. Capmatinib works by preventing the mutation and overexpression of the proto-oncogene c-MET (mesenchymal-endothelial transition), a tyrosine kinase receptor, thereby disrupting the signal transduction pathway that leads to tumor cell death. It prevents cancer cell growth, proliferation, and spread to other parts of the body.

Things to Inform the Doctor Before They Prescribe Capmatinib:

• Inform the doctor if you are allergic to any drug.
• If you have a history of systemic diseases such as diabetes, liver disease, or renal disease, inform the doctor.
• Pregnant and breastfeeding mothers should notify their doctor of their health before starting the drug.
• Women who are planning a pregnancy should tell their doctor before taking the drug.
• Patients on any medication for any condition should notify the doctor of their current and past medications.
• Tell the doctor if you have undergone any recent or previous surgeries.

Things to Do After Starting Capmatinib

• If any side effects develop, such as shortness of breath or pneumonitis, the doctor should be informed immediately so that dose modifications and tapering can be made based on the symptoms.
• Improvement in the symptoms should be reported to the doctor during the follow-up visits.
• Do not stop the drug abruptly in between without informing the doctor.
• Keep track of the improvement in health conditions.

Look Out for the Side Effects:

Common side effects due to Capmatinib:

• Nausea and vomiting.
• Confusion.
• Tiredness.
• Weakness or lethargy.
• Dark-colored urine.
• Yellowish discoloration of the skin or the white part of the eyes.
• Weight loss due to loss of appetite.
• Changes in stool color (light-colored).

Serious side effects:

• Swelling in the abdominal area.
• Cough.
• Fever.
• Shortness of breath.

The severe side effects indicate swelling of the lung tissues (pneumonitis). The drug Capmatinib also carries many other side effects. Any side effects noticed should be reported to the doctor immediately.

Dietary Alterations:

The drug Capmatinib can be taken with or without food. However, consuming a more fat-containing meal can alter the area under the graph (AUC).

What Should Be Done if a Dose Is Forgotten?

It is advised not to overdose or double the drug dose to compensate for the missed dose. Try to take the dose as soon as you remember. If it's time for the next one, take it as a regular schedule and follow the normal schedule from the next day.

What Should Be Done in Case of Capmatinib Overdose?

In case of a Capmatinib drug overdose, inform the doctor immediately and call the poison control helpline.

How to Store Capmatinib?

Capmatinib should be stored at room temperature between 20 and 25 degrees Celsius. It should be kept away from moisture.

Avoid Self-Prescription:

The drug Capmatinib should be started under a doctor's supervision. After performing the diagnostic tests, the doctor prescribes the drug dosage and schedule based on the patient's clinical history and symptoms.

Staying on Capmatinib:

• It is advised to take the drug in the actual dosage and frequency as prescribed by the doctor.
• In case of any missed dose, inform the doctor immediately.
• In case there is a worsening of the symptoms, tell the doctor.
• If there is an improvement in the health conditions, update the doctor during the follow-up visits.

For Doctors

Pharmacology of Capmatinib

Absorption:

• The plasma concentration of Capmatinib is achieved within 2 hours of oral tablet intake.
• The drug Capmatinib has an oral bioavailability of more than seventy percent.

Distribution:

The drug Capmatinib achieves a steady-state volume of distribution of 164 L.

Metabolism:

The drug Capmatinib undergoes metabolism by CYP3A4 and aldehyde oxidase.

Elimination:

• The drug is eliminated through feces (around 42 percent) and urine (approximately 22 percent).
• The half-life of Capmatinib is approximately 6.5 hours.

Toxicity:

The side effects of an overdose of Capmatinib are not well-known; however, the chances of fetal toxicity are seen according to other clinical research.

Warning and Precautions

• Capmatinib has shown severe adverse effects in patients with interstitial lung disease, so it should be used cautiously in such patients.
• An increase in alanine aminotransferase and bilirubin is seen in patients with liver disease, so caution is advised in these patients, with continuous monitoring of the patient's liver profile during treatment with Capmatinib.
• Capmatinib is toxic to the fetus, so it should be avoided in pregnant and breastfeeding mothers.

Special Considerations

• Capmatinib in Pregnant and Lactating Females:

Capmatinib is not indicated in lactating and pregnant women as it carries a risk of embryo-fetal toxicity, according to animal studies. However, much research is needed in the field.

• Capmatinib in Patients With Lung Disease:

According to the research, Capmatinib carries a risk of fatal pneumonitis or interstitial lung disease. Patients on Capmatinib should be monitored regularly for any adverse pulmonary symptoms.

• Capmatinib in Pediatric Patients:

The risk of using Capmatinib in the pediatric population is yet unknown.