What Is an EGFR Exon 20 Mutation?

Mutations can cause changes in proteins present on the surface of cells if they affect gene coding for a surface protein. One such protein is called epidermal growth factor receptor (EGFR). This protein is most commonly found on the skin cells, although it can be found anywhere in the body. The function of the EGFR protein is to help the cells grow and divide (increase in number). The EGFR protein is produced by information provided by the EGFR gene.

Normally, this gene is regulated, which means there is a switch present in the cell to turn it on when cell growth and division are needed and switch it off when not needed. In certain types of cancer, such as EGFR-positivenon-small cell lung cancer(NSCLC), a mutation in the EGFR gene causes the EGFR protein to persistently remain in the “on” position. NSLC is the most common variety oflung canceraccounting for 80 to 85 percent of the cases. The other variety is calledsmall cell lung canceraccounting for the rest of the cases oflung cancer.

The EGFR mutation causes uncontrolled cell growth (cancer). The abnormal EGFR gene is, thus, a type of tumor marker or biomarker that can be detected through lab tests. Tumor cells carrying the abnormal EGFR gene are called EGFR-positive cancer cells. This protein was the first tumor marker identified for the targeted treatment of EGFR-positive lung cancer.

EGFR-positive lung cancer is more commonly seen in

• People who have never smoked or only smoked a little
• People with a type of NSCLC cancer called lungadenocarcinoma
• Women
• Young adults with lung cancer. About 50 percent of lung cancer seen in young adults is positive for EGFR mutations.
• In people of Asian or East Asian heritage

EGFR mutations can be tested by performing a gene analysis in a lab on a sample of cancerous tissue collected from the lung (biopsy). A biopsy is the most accurate way to look for EGFR mutations. Doctors may detect EGFR mutations by collecting blood samples that may contain the tumor cells shed from thelungs. This is called liquid biopsy.

Various types of mutations can occur in the epidermal growth factor receptor (EGFR) gene depending upon the site involved in the gene. The EGFR gene has several sections (expressed as numbers) called exons. Mutations can occur on any of these exons. The most common EGFR mutations include missing genetic material (deletion) on exon 19 (19-del) or damage to exon 21 (21-L858R). These two mutations are responsible for about 85 percent of EGFR mutations seen in lung cancer. EGFR exon 20 mutations involve a specific site on the EGFR gene called the exon 20 (region on the EGFR gene that contains part of the genetic code required for the formation of EGFR protein).

Knowing the type of mutation occurring in the epidermal growth factor receptor (EGFR) gene is important for determining the treatment of non-small cell lung cancer (NSLC). For example, EGFR 19 deletion and EGFR L858R point mutations respond to targeted therapies called tyrosine kinase inhibitors (TKIs). The choice of the drug may vary depending on the specific mutation. These drugs include

• Tarceva(erlotinib)
• Iressa (gefitinib)
• Gilotrif (afatinib)
• Tagrisso (osimertinib)
• Vizimpro (dacomitinib)

Cancer with EGFR exon 20 mutations, however, does not respond to TKIs.

There are other drugs that may be used in cancer with an exon 20 mutation with more success. One such example is the drug Rybrevant (amivantamab). It is a monoclonal antibody (a lab-made version of a specific immune system protein). It targets two proteins that help cancer cells grow: EGFR and MET.