This video was recorded before the February 2021 approval of tepotinib for exon-14 skipping in MET.

When tumor tissue is looked at under a microscope, physicians can see what type of cancer it is. But physicians can also look for changes in the DNA of the tumor that might be causing the tumor to grow. Sometimes these changes are called biomarkers or molecular markers.

One way to think about it is that our DNA is like an instruction manual. If there is a typo in the instruction manual, the cell receives wrong instructions and can grow into cancer. Biomarker testing looks for those typos, so physicians know if you are a candidate to receive a targeted therapy that directly addresses those typos. 

Extra copies of the MET gene and errors in the MET protein are two biomarkers that physicians look for in non-small cell lung cancer. If you have non-small cell lung cancer, it is important to talk to your doctor about comprehensive biomarker testing to see if you have a biomarker with an approved targeted treatment. To learn more about biomarker testing, visit Lung.org/biomarker-testing

What is MET?

Right now, there are two MET biomarkers that have relevance in cancer. MET gene amplification means that there are extra copies of the gene MET in the body. Since MET is a growth receptor, having extra copies of the MET gene means that there are extra growth signals being sent to the cancer. Having extra copies of the MET gene is relatively uncommon in lung cancer, but MET amplification is a predictive biomarker for some patients. That means  if you a very high number of copies of the MET gene, you might respond better to a MET targeted therapy. 

A specific error in MET called exon 14 skipping has the most bearing on lung cancer treatment. Simply put, proteins in the cell need to be broken down and discarded or else they cause problems in the cell. When the MET protein is no longer needed, there is a protein called CBL that helps break it down. Where CBL joins with MET is encoded by a part of the MET gene called exon 14. Mutations in the MET gene that cause exon 14 to be removed (or skipped) prevent CBL from binding. This allows the MET protein to hang around longer and send growth signals that can promote cancer. 

Who is most likely to have MET alterations?

MET alterations tend to appear most in adenocarcinoma non-small cell lung cancer (NSCLC), but they can also be seen in squamous NSCLC. About 5% of lung cancer patients have MET exon 14 skipping. A lower percentage of patients have MET amplification.

How do you know if you have a MET alteration?

The best way to detect MET exon 14 skipping is through comprehensive next-generation sequencing (NGS). This type of testing places tissue from a patient’s tumor (gathered from a biopsy) in a machine that looks for a large number of possible biomarkers at one time. MET amplification can also be detected through NGS, but in some cases, a special test called FISH may be used to calculate the number of extra MET copies in cancer cells. There may be some situations where a patient can’t undergo the biopsy needed to perform NGS, and so liquid biopsy is recommended. A liquid biopsy can look for certain biomarkers in a patient’s blood. Talk to your doctor to make sure one of these tests was performed.  

Learn more about the different types of biomarker tests here.

What is the course of treatment like for someone with a MET alteration?

Standard of care for first-line treatment of MET exon 14 skipping in lung cancer that has spread is a targeted therapy MET inhibitor drug called capmatinib or tepotinib. Other lines of treatment may include clinical trials of other MET inhibitors, immunotherapy with or without chemotherapy, or off-label use of a targeted therapy called crizotinib. 

If you have MET gene amplification you may receive immunotherapy with or without chemotherapy. Other lines of treatment may include clinical trials of MET inhibitors. 

Work with your doctor to discuss your goals and options each time you have to make a treatment decision. The three big questions to ask are:

  1. What is the goal of this treatment?
  2. What are the potential side effects?
  3. What other options do I have?

Research is happening at a rapid pace and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.  

Where can I get support?

Page last updated: February 3, 2021

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