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.

What is EGFR-positive cancer?

Errors in the EGFR gene are one type of lung cancer biomarker. EGFR, which stands for epidermal growth factor receptor, is a protein located on the surface of cells that helps them grow. A mutation in the gene that codes for the EGFR protein can make cells grow too much, which can cause cancer.

There are different types of EGFR mutations. Two common ones are EGFR exon 19 deletions and EGFR L858R point mutations. The specific type of EGFR mutation tells physicians exactly where the mutation is in the DNA.

Amongst the EGFR mutations that are tested for in lung cancer, there are a few rarer 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, called tyrosine kinase inhibitors (TKIs), which are sometimes called EGFR inhibitors.

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

There are several lab tests to detect EGFR mutations. It is recommended that patients receive comprehensive next-generation sequencing (NGS). For this type of testing, tissue from a patient’s tumor (gathered from a biopsy) is analyzed to look for many possible biomarkers (including mutations) in many cancer-related genes simultaneously. There may be some situations where a patient can’t undergo the tumor 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.

Who is likely to have EGFR-positive lung cancer?

EGFR-positive lung cancer represents about 10-15% of lung cancers in the United States and most often appears in the adenocarcinoma subtype of non-small cell lung cancer. In Asian populations, the incidence of EGFR mutations is substantially higher. Patients with lung cancers with EGFR mutations tend to have a minimal to no smoking history. But EGFR mutations can appear in patients with other types of lung cancer (e.g., squamous) and smoking histories.

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

EGFR in lung cancer has been widely studied and therefore several treatment options exist. As researchers learn more, suggested treatment protocols may change. Below are general guidelines, but each patient is different, and you should work closely with your doctor to understand the most appropriate treatment for your specific type of lung cancer.

EGFR Inhibitors

EGFR inhibitors block the activity of the EGFR protein. They 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 a way 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 mutation that will help your doctor know which treatment to suggest next. Examples of EGFR-inhibitors include: osimertinib (Tagrisso), afatanib (Gilotrif), erlotinib (Tarceva), and lazertinib (Lazcluze).

Combination Therapies

In some instances, your doctor may recommend combining an EGFR inhibitor with a different type of therapy as an initial treatment for your lung cancer. Combinations may include osimertinib (Tagrisso) combined with chemotherapy or lazertinib (Lazcluze) combined with a medication called amivantamab (Rybrevant). Amivantamab is an antibody-based therapy that blocks the EGFR protein on the surface of cancer cells.

For lung cancer with EGFR exon 20 insertions, the combination of amivantamab and chemotherapy is generally used for initial treatment.

Early vs. Late-Stage Treatment

EGFR-positive lung cancer caught at an early stage may be removed through surgery. Certain patients may receive osimertinib (Tagrisso) after surgery and some patients may receive chemotherapy.

Treatment for later-stage EGFR-positive lung cancer depends on the type of EGFR mutation present and how the cancer progresses.

• First-line treatment for EGFR exon 19 deletions or exon 21 L858R point mutations is osimertinib (Tagrisso) alone or in combination with chemotherapy or the combination of lazertinib (Lazcluze) and amivantamab-vmjw (Rybrevant) (an antibody-based therapy).
• First-line treatment for EGFR S7681, L861Q or G719X mutations is afatanib (Gilotrif) or osimertinib (Tagrisso).
• First-line treatment for EGFR exon 20 Insertions is chemotherapy with amivantamab (Rybrevant).

Second-line treatment for EGFR mutations may include some combination of other targeted drugs, chemotherapy and immunotherapy.

Other considerations

• Patients with EGFR-positive lung cancer should ask their physicians about participating in a clinical trial.
• Brain surgery and/or brain radiation therapy may be options for patients whose lung cancer has spread to the brain (brain metastases).

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.