A pproximately 541,000 people in the United States have lung cancer, according to the American Lung Association. The most common type, non-small-cell lung cancer (NSCLC), accounts for 80 to 85 percent of cases, according to the American Cancer Society.
About one in four people with NSCLC have tumor DNA with a mutation in the epidermal growth factor receptor (EGFR) gene, according to an analysis of data from more than 150 studies published in August 2015 by the American Journal of Cancer Research. More than 70 different EGFR mutations have been identified, and specific drugs — known as targeted therapies — have been approved to treat many of them.
Before you ask your doctor about the best treatment for EGFR-positive NSCLC, do your homework! It’s important to be an active participant in your care, and a big part of that is educating yourself about your options for genetic testing and targeted treatment in order to work with your oncologist to make informed treatment decisions.
We’re here to help: Here’s what you should know about EGFR-positive NSCLC and how targeted treatments work.
The Role of Genetic Testing in Treatment Selection
When you’re diagnosed with lung cancer, the next step will likely be to have a type of genetic test called next-generation sequencing, explains Keith Eaton, MD, PhD, an oncologist at Seattle Cancer Care Alliance and a professor of oncology at the University of Washington School of Medicine. This helps doctors know if the cancer tumors have mutations or alterations that are known to drive cancer growths, he says.
Among the many possible mutations is one on the epidermal growth factor receptor (EGFR) gene. If you test positive for that, it means you have EGFR-positive NSCLC.
EGFR is a protein found on the surface of both healthy and cancer cells. When the protein is damaged because of a genetic mutation, it doesn’t perform the way it should, causing rapid cell growth and helping the cancer spread.
Although there are more than 70 different EGFR mutations in NSCLC, most are caused by alterations in exon 19 and exon 21, with exon 18 and exon 20 mutations being less common and more difficult to treat.
Once genetic testing has determined that you have an EGFR mutation, and identified the specific type, your oncologist may prescribe a targeted drug therapy to help slow the growth of cancer cells. Although these drugs won’t cure your lung cancer, they can help slow progression of the disease and delay the onset of serious symptoms.
Facts About Treating EGFR-positive NSCLC
Learning more about EGFR-positive NSCLC and the targeted therapies available to treat it can help you feel a bit more comfortable as you begin or refine your treatment.
1. There are six targeted therapies available for treating EGFR-positive NSCLC.
Several targeted therapies have been approved by the FDA for the treatment of specific EGFR mutations in NSCLC. They’re broken out into two categories:
- afatinib (Gilotrif)
- erlotinib (Tarceva)
- gefitinib (Iressa)
- mobocertinib (Exkivity)
- osimertinib (Tagrisso)
- aminantamab-vmjw (Rybrevant)
“Osimertinib is currently the standard of care first-line treatment for EGFR mutated NSCLC in the metastatic setting,” meaning the cancer has spread beyond the lungs, says Heather Katz, DO, FACOI, FACP, an oncologist at Phelps Hospital, Northwell Health in Sleepy Hollow, New York, and assistant professor at Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. It’s also approved for use in people who have had NSCLC tumors removed with surgery.
Other options, like mobocertinib and aminantamab-vmjw, aim to treat mutations resistant to other targeted drugs, like the exon 20 mutation.
2. Early identification of EGFR mutations help offer a more personalized treatment approach.
EGFR-positive lung cancer was previously checked for only in people with stage IV, or advanced, disease, according to Dr. Katz. However, more recently, doctors check for EGFR mutations in the earlier stages to see if people can benefit from targeted treatment. Earlier-stage lung cancer is typically treated with surgery to remove tumors, and possibly with radiation and chemotherapy. Since it means the cancer has spread beyond the lungs, later-stage, or metastatic, lung cancer is often treated with systemic therapy, which includes chemotherapy, immunotherapy, and targeted therapy. “We check different mutations — especially in the advanced settings — to see if we can give targeted treatment and have a more personalized approach,” Katz says. According to a September 2021 study published in the journal Nature, identifying the specific EGFR mutation in NSCLC can help your care team develop a more effective plan to help manage the spread of the cancer and lessen the symptoms.
3. The EGFR mutation means your body is activating a signal for cancer cells to grow in the lungs.
When the cells in your body think they’re supposed to continuously grow, they can start doing so uncontrollably, meaning cancer occurs, Dr. Eaton says. “EGFR is what we call a driver mutation,” he explains. “A driver is a gene that’s part of your normal cell but will turn off and on in response to outside stimuli. But because of a genetic mutation, it’s stuck on.”
The purpose of targeted treatments in EGFR-positive NSCLC is straightforward: to turn off the cell signaling in the EGFR gene, thus reducing the amount of cancer cells in the body, adds Katz.
4. There are different EGFR mutations.
Over 70 types of EGFR mutations have been identified. They’re classified by which exon is altered. Exons are a segment of DNA coding that contain information for a protein sequence. So far, treatments have been developed for mutations affecting exon 18, exon 19, exon 20, and exon 21.
5. These genetic mutations are not inherited.
When people think of genetic mutations, many assume they’re conditions passed down through families. While the risk for some types of cancer can be inherited, EGFR mutations don’t fall into this category. Instead, they occur randomly. In the case of EFGR mutations, “there’s something that was a spontaneous mutation in the tumor,” Eaton says.
6. Most targeted treatments are administered orally, with one exception.
All the TKI treatments are taken as a pill. The pill is taken once a day, with or without food. Unlike chemotherapy pills, which are often taken in rounds, these targeted treatments are taken on an ongoing basis. “Typically, it’s continuous until either intolerable toxicity or progression of the disease,” Katz says.
However, the monoclonal antibody, amivantamab-vmjw, is administered as an intravenous (IV) infusion weekly for the first four weeks of treatment, then every two weeks thereafter, usually in an infusion clinic.
7. Side effects are generally mild and easy to manage.
EGFR is also present in healthy cells, including in the skin, according to Jack Jacoub, MD, an oncologist and medical director of MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, California. As a result, targeted treatment for EGFR-positive NSCLC can cause a skin rash. Another common side effect is diarrhea. Fortunately, these symptoms are easy to treat, and probably don’t require stopping treatment altogether. “Sometimes you have to hold the medication and give an opportunity for the problems to get better, and then restart the medication at a lower dose,” Dr. Jacoub says. A rare side effect of targeted therapy is lung inflammation — when that happens, it’s necessary to stop treatment, he adds.
8. These treatments are expensive, but there is financial help.
EGFR targeted treatments can cost up to $15,000 a month, Eaton says. “But most insurance covers it,” he adds. “Sometimes there’s a high copay, and many times patients with that high copay will qualify for patient assistance.” The manufacturers of each respective medication offer financial assistance for those who qualify, which you can find on the drug manufacturer’s website.
9. Targeted treatments can extend both quality and quantity of life.
Although late-stage lung cancer generally can’t be cured, targeted treatments have been shown to slow progression and prolong life expectancy. “On average, people are living a year and a half to two years longer on these drugs,” Jacoub says. “That’s an average, but there’s a good percentage of patients that live even longer.” The treatments also help prevent cancer symptoms from progressing, which helps improve quality of life during that time as well.
9 FAQs About Targeted Treatments for EGFR-positive NSCLC, Answered
Managing EGFR-positive NSCLC Symptoms and Treatment Side Effects
Dealing with both the symptoms of lung cancer and the side effects of treatment can be tough. Symptoms of later-stage lung cancer can include a persistent cough, a hoarse voice, loss of appetite, and shortness of breath, according to Jacoub. And typical side effects of targeted treatments for EGFR include diarrhea and skin rash, he adds.
Here are some ways to manage these common challenges:
In the case of more serious treatment side effects — such as lung inflammation — doctors can offer supplemental oxygen, antibiotics, or steroids if needed, Katz adds. You may also need to stop treatment.
If you experience these or other symptoms, don’t hesitate to let your doctor know. “The important thing is open and honest communication, and to ask questions,” Eaton notes.
Next Steps: Making Treatment Decisions
You’ve learned a lot about targeted treatments for EGFR-positive NSCLC. So, what’s next?
Take some time to absorb all this information and decide on your next steps.
Before your next appointment, take some time to reflect on how you’re feeling about your diagnosis and potential treatment options. Think about:
- What are my goals for treatment?
- How have EGFR-positive NSCLC symptoms affected my quality of life to date?
- What are my biggest concerns as I begin treatment for EGFR-positive NSCLC?
Fully understanding your options and your treatment plan will help you get the most of your NSCLC treatment. Consider asking your doctor these questions:
- Which treatment are you prescribing for me? Why?
- What other facts do I need to know about targeted treatments before I take them?
- What can I do to get ready for treatment?
- What types of results do you expect? How soon might I notice them?
- If I’m concerned about the costs and insurance coverage for my treatment, what can I do?
- When should I come back to evaluate any progress?
- What are next steps if this treatment isn’t working as well as we’d hoped?