EGFR and Lung Cancer

The videos above were produced in 2021. For the latest treatment options, speak with your doctor.

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. When there is a mutation, or change, in the EGFR gene, the EGFR protein makes cells grow too much, which can cause cancer.

There are different types of EGFR mutations. The two most common are EGFR exon 19 deletions and EGFR L858R point mutations. These specific types of EGFR mutations tells doctors exactly where the change occurred in the DNA.

In addition to these common mutations, there are rarer EGFR mutations that are tested for in lung cancer that may require different treatment. One major example of this in is EGFR exon 20 insertions mutations, which does not respond to the typical treatment for EGFR-positive lung cancer, called tyrosine kinase inhibitors (TKIs), also known as EGFR inhibitors.

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

There are several lab tests that can detect EGFR mutations. It is recommended that patients receive comprehensive next-generation sequencing (NGS), also known as comprehensive biomarker testing. 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. In some situations, a patient may not be able to have the tumor biopsy needed to perform NGS testing, so a liquid biopsy may be 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 (NSCLC). The incidence of EGFR-positive lung cancer is higher in Asian populations. Patients with lung cancers with EGFR mutations typically have a minimal to no smoking history, although, EGFR mutations can appear in patients with other types of lung cancer (e.g., squamous NCSCLC) and those with smoking histories.

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

EGFR-positive lung cancer has been widely studied, and therefore several treatment options exist. As researchers learn more, treatment recommendations may change. Below are general guidelines, but each patient's situation is unique. Work closely with your doctor to decide the most appropriate treatment for your specific type of lung cancer.

EGFR Inhibitors

EGFR inhibitors work by blocking the activity of the EGFR protein, often controlling the cancer. Depending on the patient and specific drug, these EGRF inhibitors can control the cancer for several months, or even years, but they are not a cure.

Over time, 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 cases, your doctor may recommend combining an EGFR inhibitor with a different type of therapy as part of the 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.

The combination of the EGFR inhibitor erlotinib (Tarceva) and the anti-angiogenic agent ramucirumab (Cyramza) is FDA-approved for initial treatment of patients with EGFR exon 19 deletions or exon 21 L858R mutations. Adding ramucirumab may help slow resistance to EGFR-targeted therapy.

For lung cancer with EGFR exon 20 insertion mutations, 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 often be treated with surgery to remove the tumor. Certain patients, particularly stage III NSCLC, may receive osimertinib (Tagrisso) after surgery or chemoradiation, and some patients may receive chemotherapy exclusively.

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). Dacomitinib (Vizimpro) is a second-generation EGFR inhibitor approved as a first-line treatment for EGFR exon 19 deletions or exon 21 L858R mutations. It may be an option for some patients, especially those who are not eligible for newer third-generation EGFR inhibitors.
• 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). Sunvozertinib (Zegfrovy, Dizal (Jiangsu) Pharmaceutical Co., Ltd.) is also available for EGFR exon 20 insertions, as detected by an FDA-approved test (Oncomine Dx Express Test), for individuals whose disease has progressed on or after platinum-based chemotherapy.
• Datopotamab deruxtecan (Dato-DXd) is approved for adult patients with EGFR-mutated non-small cell lung cancer (NSCLC) who have progressed after prior treatment with an EGFR inhibitor and platinum-based chemotherapy.

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.