EGFR-Mutant Lung Cancer: What You Need to Know

April 5, 2021

While most lung cancers are linked to tobacco smoking, a minority — about 15 percent in the United States — of non-small cell lung cancers are driven by a random mutation in a gene called EGFR, which helps cells grow and divide.

What is EGFR-mutant lung cancer?

A mutation in the gene EGFR, which stands for epidermal growth factor receptor, causes cells to grow without normal controls and form tumors.

EGFR mutations usually occur during the patient’s lifetime, although in a small number of cases the EGFR mutation can be inherited from a parent. EGFR mutations are found more frequently in never-smokers but can also occur in former smokers.

All lung cancer patients seen at Dana-Farber undergo testing for lung cancer-associated mutations, and if an EGFR mutation is identified the patient is referred to Dana-Farber’s Chen-Huang Center for EGFR-Mutant Lung Cancers. Patients seen at the center for EGFR mutant lung cancer are followed for direct care with the goal of improving the lives of patients and advancing research into the disease.

The Center’s director, Pasi Jänne, MD, PhD, was one of the scientists who discovered the role of mutant EGFR in some cases of non-small cell lung cancer and showed that the tumors responded to a drug targeting the EGFR protein. Dana-Farber was one of the first in the United States to routinely test lung cancer patients for EGFR mutations; since then, it has become the standard of care worldwide.

Cathleen Power, MSN, APRN-BC, a nurse practitioner in the Center, says patients diagnosed with EGFR-mutant non-small cell lung cancer often ask how the mutation occurred.

“We explain that it was likely caused by a random mutation in a cell after they were born, although occasionally it can be a germline mutation that occurs in a sperm cell or an egg cell and is passed directly from a parent to a child at the time of conception,” she notes.

Pasi Janne, MD, PhD, and Cathleen Power, NP.

How is EGFR-mutant lung cancer treated?

Treatment is determined by genetic testing, which allows oncologists to know if your lung cancer cells carry EGFR mutations.

Some early lung cancers can be removed by surgery, but if the cancer is at an advanced stage, initial treatment is usually an oral inhibitor drug targeted to the overactive EGFR protein. Targeted therapy improves responses and progression-free survival compared with chemotherapy in patients with advanced EGFR-mutant lung cancer. Some drugs used to target mutant EGFR include osimertinib (Tagrisso), afatinib (Gilotrif), gefitinib (Iressa), and erlotinib (Tarceva). These powerful EGFR inhibitors can have side effects, including skin rashes and dryness, and diarrhea. Power’s mission is to standardize symptom management for patients in a system that includes dermatologists and gastrointestinal specialists, as well as neurologists if the lung cancer metastasizes to the brain.

While currently available targeted drugs can shrink advanced lung cancers for several months or more, the tumors sooner or later develop resistance to the targeted therapies that allows the cancer to grow again. When a targeted drug no longer is able to control the patient’s tumor, a biopsy of the cancer may be taken and analyzed to look for DNA changes causing the resistance. Many times these changes can also be identified in the blood using a “liquid biopsy.

“About 30 percent of the time we can identify the resistance mutation,” says Power, potentially enabling physicians to prescribe another drug that targets that mutation or offer participation in a clinical trial that  is specifically evaluating new strategies to overcome drug resistance.

Many patients seen in the Chen-Huang Center are offered clinical trials aimed at finding improved treatments for EGFR-mutant lung cancer. Currently, clinical trials are focused on enhancing the benefits of initial targeted therapy and evaluating new approaches to therapy when the initial EGFR inhibitors stop working.

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