EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC)

This page is for people with non-small cell lung cancer whose tumor has an EGFR mutation, and for their families. It explains what the result means, which treatments fit, and which warning signs need a fast call.

EGFR stands for epidermal growth factor receptor. It is a protein on the surface of cells that tells them to grow. In some non-small cell lung cancers, the EGFR gene is mutated and the receptor gets stuck in the on position. This happens most often in adenocarcinoma. That single change drives the cancer. It is also what makes the cancer a target.

The tumor usually picks up this mutation during life. NCI explains that these somatic changes can't be passed on to family members. ACS says EGFR mutations are found in about 10% to 20% of non-small cell lung cancers. They are more common in people who don't smoke, in women, and in Asian people. But they occur in every group.

Two common changes are an exon 19 deletion and the L858R change in exon 21. These are the mutations studied in major osimertinib trials. Exon 20 insertions are treated differently and are covered below.

Because EGFR changes the treatment plan, you need to know your result early. Biomarker testing looks at tumor tissue, sometimes paired with a blood test for circulating tumor DNA. It looks for EGFR and other targets such as ALK, KRAS, BRAF, RET, MET and HER2.

Ask whether results should be back before treatment starts. Ask which test was ordered. Ask whether it detects exon 20 insertions, and when results are due.

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor. You take it as a daily pill.

It is used in several settings:

• Advanced or metastatic disease, as first-line treatment, and in some cases combined with chemotherapy.
• After surgery, as adjuvant treatment for early-stage disease, based on the ADAURA trial.
• After chemoradiation, for stage III disease that cannot be removed with surgery and has not grown during or after chemoradiation, based on the LAURA trial.
• After another EGFR pill stops working, for cancer that has spread.

Older EGFR inhibitors are still used in some situations. These include erlotinib, gefitinib, afatinib and dacomitinib. Amivantamab with lazertinib is another approved first-line option. ACS lists common side effects of EGFR inhibitors as skin problems, nail changes, tiredness, loss of appetite, nausea, vomiting and diarrhea. Rare but serious ones include lung inflammation (pneumonitis), heart muscle damage and heart rhythm changes. Report side effects early.

If your report says EGFR exon 20 insertion, treatment follows its own path. Amivantamab is a bispecific antibody. It is approved with chemotherapy as first-line treatment, and on its own after chemotherapy. This is why the exact variant on your report matters, not just the words "EGFR positive."

Immune checkpoint inhibitors are used for many lung cancers. They include pembrolizumab, nivolumab and atezolizumab. ACS says that if a gene such as EGFR is mutated, your first treatment will likely be a targeted therapy drug.

If immunotherapy is suggested because of a high PD-L1 score, ask how that fits with your EGFR result. That is a fair question.

Over time, an EGFR drug may stop controlling the cancer. If scans change, ask whether repeat testing of tissue or blood could help choose the next step.

Asking about clinical trials at each turning point is normal and expected. It is not a sign that options have run out.

The pills are easy to take at home, which makes it easy to sit on a problem. A few signs should not wait.

• Call 911 or go to an emergency department if breathing suddenly gets harder, you have chest pain, or your heart pounds or races and you feel lightheaded or close to fainting. MedlinePlus lists these among the osimertinib effects needing emergency care. Swollen ankles or feet with breathlessness belong here too. Do not drive yourself.
• Call your cancer team immediately if you have a fever of 100.4°F (38°C) or higher. CDC says to call your doctor immediately at this temperature if you are on chemotherapy. A fever can be the only clue to an infection, and infections during chemotherapy can be life-threatening. MedlinePlus lists fever on osimertinib as a serious side effect too. Call at any hour. If you go to an emergency room, tell the staff right away that you are on treatment for lung cancer.
• Call your care team right away if you have a new or worse cough or shortness of breath. Lung inflammation from an EGFR inhibitor is rare but serious. For trouble breathing, call 911.
• Call your care team right away if the skin rash blisters or peels. MedlinePlus lists this as a serious side effect of osimertinib. Also call right away if your eyes turn red, watery, painful or sensitive to light, or your vision changes.
• Call your care team within a day or two if diarrhea is not settling with what you were given. Do not simply stop the tablet on your own. Tell the team first.

• FDA: osimertinib for unresectable stage III NSCLC after chemoradiation
• FDA: amivantamab-vmjw for EGFR exon 20 insertion NSCLC
• NCI: Osimertinib Improves Survival in Lung Cancer (ADAURA)
• NCI drug information: osimertinib
• FDA: lazertinib with amivantamab-vmjw for NSCLC
• American Cancer Society — Targeted Drug Therapy for Non-small Cell Lung Cancer
• American Cancer Society — Treatment Choices for Non-small Cell Lung Cancer, by Stage
• American Cancer Society — Tests for Lung Cancer
• National Cancer Institute — Biomarker Testing for Cancer Treatment
• MedlinePlus drug information: osimertinib
• CDC — Watch Out for Fever (Preventing Infections in Cancer Patients)