EGFR and Lung Cancer

Support for this educational program provided by Amgen, AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, Genentech, Lilly Oncology, Merck, Novartis and Pfizer.

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. 

A mutation in the EGFR gene is one biomarker 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 an EGFR mutation or another biomarker. The results of this testing influence your treatment options. To learn more about biomarker testing, visit Lung.org/biomarker-testing. 

What is EGFR-positive cancer?

EGFR (epidermal growth factor receptor) is a protein on cells that helps them grow. A mutation in the gene for EGFR can make it grow too much, which can cause cancer.  

There are different types of EGFR mutations. If you think of a mutation as a typo in the DNA, you can have missing or added words in the DNA, sometimes called deletions or insertions. You can also have places where the DNA is misspelled, which is called a point mutation. 

On your test results you might see that you have an EGFR 19 deletion or an EGFR L858R point mutation (the most common type of EGFR mutations that we know of). That information helps tell physicians exactly where the typo is in the DNA. EGFR 19 deletions and EGFR L858R point mutations are typically treated the same way. 

Amongst the EGFR mutations that are tested for in lung cancer, there are a few rare types that are treated differently than the more common EGFR mutations. The major example of this in lung cancer is EGFR exon 20 insertions. This is a type of EGFR mutation that doesn’t respond to the typical treatment for EGFR-positive lung cancer, which are called tyrosine kinase inhibitors, or TKIs. 

How do you know if you have EGFR-positive lung cancer?

In general, there are two ways to detect EGFR mutations. The best way 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. 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.

Who is likely to have EGFR-positive lung cancer?

EGFR-positive lung cancer represents about 10-15% of lung cancer in the United States and generally appears in  adenocarcinoma subtype of non-small cell lung cancer. Patients with lung cancers with EGFR mutations tend to have minimal to no smoking history. But EGFR mutations can appear in lung cancer patients with different subtypes and smoking histories.  

What are the treatment options for someone with EGFR-positive cancer?

Knowing if you have EGFR-positive lung cancer has the most treatment implications for stage four patients. Most patients with stage four EGFR-positive lung cancer will likely be prescribed a pill called an EGFR targeted tyrosine kinase inhibitor (TKI) or EGFR-inhibitor to begin with. In addition to patients with stage 4 lung cancer, patients with stage IB-III lung cancer who have had their lung cancer removed through surgery are also eligible to receive an EGFR inhibitor after surgery.

The choice of a particular EGFR inhibitor depends on your oncologist’s preference, your specific type of lung cancer, and your treatment goals. Talk through the pros and cons of each option with your doctor. In general, based on studies showing that osimertinib is better tolerated and more effective than other EGFR inhibitors (erlotinib, gefitinib), most patients will receive osimertinib as their first EGFR inhibitor.

EGFR inhibitors can often control the cancer for several months or even multiple years depending on the patient and the drug, but it will not cure the cancer. Ultimately the cancer learns away around these treatments, which is called “acquired resistance”. When this happens, it is recommended that your doctor repeat biomarker testing, either through a tissue or liquid biopsy to see if you have a new biomarker or mutation that will help your doctor know which treatment to suggest next. 

Below are the treatments available for EGFR-positive lung cancer patients. 

Tyrosine Kinase Inhibitors (TKIs)

• Afatinib (approved for stage 4 lung cancer)
• Dacomitinib (approved for stage 4 lung cancer)
• Erlotinib (approved for stage 4 lung cancer)
• Gefitinib (approved for stage 4 lung cancer)
• Osimertinib (approved for stage 1-4 lung cancer)

Others treatment options for EGFR-positive lung cancer include:

• Ramucirumab with Erlotinib. 

Ramucirumab is a medication given through an IV that works with the EGFR-inhibitor to control the cancer. Ramucirumab blocks proteins needed by cancer cells to form blood vessels to help support their growth and spread.

• Chemotherapy 

Exon 20 Insertions

• Patients with EGFR exon 20 insertions may receive chemotherapy, immunotherapy or the targeted therapy drug Amivantamab-vmjw.

EGFR Inhibitors after Surgery

• Some EGFR-positive patients whose lung cancer is caught early may be eligible for surgery to remove the tumor. 
• To keep the cancer from coming back, some patients may be given chemotherapy followed-by osimertinib (an EGFR inhibitor pill). 

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.