What Is Met Exon 14 Skipping in Non-Small Cell Lung Cancer?

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MET exon 14 (METex14) skipping is an uncommon gene mutation found in non-small cell lung cancer (NSCLC). Patients with this mutation may respond well to treatments that target the gene alteration. METex14 skipping accounts for approximately 3% to 4% of metastatic NSCLC.

MET is short for the mesenchymal-epithelial transition gene. It helps cells grow and survive. When this gene mutates, cancer cells grow faster than usual.

Patients with METex14 in NSCLC face a poor prognosis, as many have cancer which has spread to the bone, liver, or brain. But new and targeted treatments for METex14 may hold the key to managing symptoms and prolonging life.

Genetic test in lab

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Symptoms

METex14 is most common in people with lung adenocarcinoma, a type of NSCLC. This type of cancer usually begins near the outer portion of the lungs away from the airways. Symptoms often don’t begin until the cancer has spread toward the center of the lungs.

When symptoms do appear, they include:

  • A cough that does not go away or gets worse
  • Coughing up blood or rust-colored sputum (spit or phlegm)
  • Chest pain that is often worse with deep breathing, coughing, or laughing
  • Hoarseness
  • Loss of appetite
  • Unexplained weight loss
  • Shortness of breath
  • Feeling tired or weak
  • Infections such as bronchitis and pneumonia that don’t go away or keep coming back

Because it can take time for symptoms to appear, it is common for this type of cancer to be missed until it reaches an advanced stage.

Causes

METex14 is present in about 3% of people with NSCLC, which equates to around 4,000 to 5,000 patients per year in the United States.

The types of mutations present in lung cancers vary depending upon the type of lung cancer. The METex14 mutation is most common in people with lung adenocarcinoma, but in rare cases it has been found in squamous cell carcinoma of the lungs (another type of NSCLC) and small cell lung cancer.

METex14 isn’t a hereditary mutation like the BRCA mutations found in some people with breast and other cancers. People who have lung cancer cells positive for METex14 weren’t born with cells that had this mutation and didn’t inherit this mutation from their parents.

Patients with METex14 are generally older (median age, 65 to 76 years), more often female, and less likely to have a history of smoking compared with those without METex14.

Diagnosis

METex14 and other gene mutations are diagnosed through genetic testing (also known as molecular profiling). Doctors obtain a sample of a lung tumor via a tissue biopsy or may examine a blood sample obtained via a liquid biopsy. These samples are checked for markers that show the METex14 mutation is present.

Your hospital or a lab tests the sample for genetic changes and proteins that are linked to lung cancer.

Several organizations have worked together to develop guidelines on genetic testing in lung cancer. The consensus is that all patients with advanced-stage lung cancer should be tested for METex14 and other treatable genetic mutations, regardless of sex, race, smoking history, and other risk factors.

Treatment

Treatment for NSCLC depends on the size of the cancer and how far it has spread in the body. Treatment can include one or a combination of:

MET inhibitors are a new type of targeted therapy for lung cancer that tests positive for METex14. These drugs work by blocking a substance the tumor needs to grow.

There are currently two drugs approved by the Food and Drug Administration (FDA) to target METex14 lung cancer:

  • Capmatinib (Tabrecta)
  • Tepotinib (Tepmetko)

These types of drugs are known as MET inhibitors. They work by attacking the MET protein. These drugs can be used to treat metastatic NSCLC if the cancer cells have certain types of MET gene changes. 

Lung cancers may initially respond very well to targeted therapy medications. However, patients can become resistant to the medication over time.

If you develop resistance to a MET inhibitor, your doctor will try a new medication or a combination of medications. New medications continue to be studied in clinical trials for people who develop resistance.

Side Effects of MET Inhibitors

Common side effects can include:

  • Swelling in the hands or feet
  • Nausea or vomiting
  • Feeling tired or weak
  • Loss of appetite
  • Constipation or diarrhea
  • Changes in certain blood tests
  • Joint and muscle pain

Less common but more serious side effects can include inflammation (swelling) or scarring in the lungs, which can make it hard to breathe, as well as liver damage.

Prognosis

While the overall five-year survival rate for NSCLC is about 25% and only 7% for advanced-stage lung cancer, researchers are constantly looking for effective treatments to improve these statistics.

METex14 lung cancer tends to be aggressive, growing and spreading fairly rapidly. But it does respond to targeted therapy.

Research found that 68% of people who took capmatinib as their first treatment had a partial or complete response to the drug. This response lasted for an average of one year. Additionally, 41% of people who’d already been treated with chemotherapy or other drugs responded to capmatinib.

Among patients with advanced NSCLC with a confirmed METex14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients.

The treatment of METex14 NSCLC with targeted therapy is not aimed at curing cancer, but it can help you live a longer, more satisfying life by managing symptoms and stopping its spread.

Summary

When you’re diagnosed with NSCLC, molecular testing can identify genetic mutations, like METex14 skipping. Advanced NSCLC offers a poor prognosis, but targeted drugs (capmatinib and tepotinib) are approved by the FDA to treat cancers with METex14 mutation.

A Word From Verywell

Hearing you have lung cancer with a genetic mutation such as METex14 can sound scary, particularly if you look at the survival statistics.

However, FDA-approved targeted therapies are available, with more in development. Clinical trials are also ongoing if you are well enough to participate. Speak to your healthcare provider about the treatment options available to you.

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10 Sources
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