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What Is EGFR-Positive Lung Cancer?
Epidermal growth factor receptor (EGFR) protein sits on the surface of your lung cells to help them grow.
Some cells can grow very quickly and make mistakes. If this happens to lung cells, the gene code for the EGFR protein can get mutated.
EGFR mutations can cause your lung cells to grow too much, leading to cancer, also called EGFR-positive lung cancer.
What is EGFR-positive non-small-cell lung cancer (NSCLC)?
About 10% to 15% percent of all lung cancers in the United States are EGFR-positive, most of which are non-small-cell lung cancer (NSCLC).
NSCLC grows from the cells that line the airways in your lungs.
Up until recently, this sort of cancer had a very poor survival rate.
After diagnosis with advanced disease, we saw a survival time of about eight months. Now, many people live for four or five years.
Just a decade ago, less than 15 people out of 100 lived for five years with advanced EGFR-positive NSCLC.
Today, the five-year survival rate has risen.
About 34 people out of 100 live at least five years after a diagnosis of advanced EGFR-positive lung cancer.
As we develop newer and better treatments, we hope that people will routinely live longer than that.
We're really in a golden age when it comes to EGFR-positive lung cancer.
Who's at Risk for EGFR-Positive Lung Cancer?
EGFR-positive lung cancer can occur in anyone, but it usually happens if you've had a specific type of NSCLC called adenocarcinoma.
You're more likely to develop EGFR-positive NSCLC if you are:
- From East Asia
- Female
- Not a smoker
- A young adult
In fact, about half of lung cancers in young adults have EGFR mutations. But there are also different types of EGFR mutations.
The two most common ones are EGFR exon 19 deletions and EGFR L858R point mutations — they make up about 88%.
Other, rare mutations include:
- EGFR exon 20 insertions
- G719X
- L861Q
- S7681
Although these gene changes are much less common, over 30,000 NSCLC lung cancer cases diagnosed each year have one of these EGFR mutations.
Ask your doctor to test your tumor for an EGFR mutation if you're diagnosed with NSCLC, especially if it's adenocarcinoma.
We want to know not only if you have an EGFR mutation, but what type you have. Because some tumors respond better to certain treatments.
Unique Treatment Journey for EGFR-Positive NSCLC
A lung biopsy may be part of your lung cancer diagnosis. Your doctor removes a small piece of lung tissue to test under a microscope and look for cancer.
If you have adenocarcinoma, it's important to request full, next-generation sequencing (NGS). This special test can check for certain DNA changes in your cancer cells like EGFR.
Your doctor can usually use the same biopsy tissue to check for EGFR mutations.
But if the lab didn't get enough, your doctor can do a liquid biopsy. They'll take a sample to check for any cancer cells.
After your EGFR mutation diagnosis, you and your cancer care team will make a treatment plan geared to your specific cancer stage and mutation.
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What Is Early-Stage Treatment?
Early-stage treatment refers to EGFR-positive NSCLC that's stage I, II, or III.
Treatment for earlier stages for NSCLC have changed dramatically over the last few years.
In the old days, we'd do surgery if we could, and then sometimes follow it with chemotherapy.
EGFR Inhibitors
These targeted treatments can block EGFR signals for cancer cell growth. After surgery, osimertinib (Tagrisso) is one of the most commonly used medicines. It's given at stage IB to IIIA NSCLC cancer.
Research shows it can greatly improve five-year survival rates, compared to those who don't take the therapy.
Older EGFR Inhibitor Treatments
Osimertinib has been the standard of care for most EGFR-positive lung cancers since its approval in 2015. It's both a kinase and EGFR inhibitor.
"Earlier medicines only lasted for nine to 13 months, while the effects of osimertinib seem to persist for at least three or four years," says Heymach. "It permanently attaches to the EGFR gene, which means it may prevent the protein from ever growing again."
Other, older medicines called kinase inhibitors include:
- Afatinib (Gilotrif)
- Erlotinib (Tarceva)
- Dacomitinib (Vizimpro)
- Gefitinib (Iressa)
"Osimertinib also appears to carry fewer side effects than previous medications," says Heymach. "Patients have less rash and diarrhea and are better able to carry out normal activities."
Chemotherapy
Chemotherapy can also help early-stage EGFR-positive cancer, says Salgia:
- Before surgery, to help shrink the tumor
- Along with radiation, to treat large stage III tumors that can't be removed with surgery
Treatment With Osimertinib
Jessie Creel, 43, was diagnosed with stage IV EGFR-positive NSCLC on Nov. 20, 2024, a week before Thanksgiving.
"I got a call that told me the cancer had metastasized to my brain while I was in Austin to celebrate the holiday with my entire extended family," says Creel, a mother of three who lives in San Clemente, California.
Creel's cancer doctor recommended that she start taking osimertinib (Tagrisso), which was FDA approved in 2015 to treat advanced EGFR-positive NSCLC.
What is osimertinib?
Osimertinib is known as a targeted therapy. The medicine targets mutated forms of the EGFR protein, which can drive NSCLC cancer cell growth.
How Does Resistance and Transformation Happen?
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While osimertinib has been a game changer for treatment of EGFR-positive cancers, it doesn't always continue to work, says Heymach.
The main reason the medicine stops working? Your cancer cells can develop more EGFR gene changes (mutate) and become resistant to treatment.
Osimertinib irreversibly attaches itself to EGFR like a lock and key.
But sometimes, the place on the gene where the medicine attaches mutates. And that means the medicine can't stick there anymore.
It's like a keyhole changes, so the key can no longer fit into it.
Other Possible Gene Changes
If your cancer cells stop responding to treatment, your cancer doctor will order a repeat biopsy.
They'll look for new EGFR mutations as well as other gene changes, too.
T790M mutation
If you've been treated with an EGFR inhibitor before, such as erlotinib or gefitinib, you can get this mutation. "We don't see this as much anymore, simply because most patients are put on osimertinib after diagnosis," says Heymach. Most people usually start out on osimertinib.
C797S mutation
This is a mutation that can develop after using newer EGFR inhibitors like osimertinib. It happens about 6% to 12% of the time. But your doctor may suggest using a first-generation medication like gefitinib or erlotinib. They can work well, but they may come with more side effects.
Met amplification
Cancer cells can get multiple copies of the MET gene, which allows them to grow, divide, and spread.
If this happens, your doctor may want to treat you with both an EGFR inhibitor and another type of medicine called a MET inhibitor, like tepotinib (Tepmetko).
Early research suggests this combination works very well.
Transformation to SCLC
Anywhere from 5% to 15% of EGFR-positive lung cancers stop responding to treatment when the tumors transform to small-cell lung cancer (SCLC).
Your cancer can become (transform) another type of cancer for many reasons, like proteins stop working.
If tumor suppressor proteins like RB1 or p53 stop working, cancer cells can grow very quickly and change into other cancer types.
Small-cell lung cancer is one type of cancer that's more aggressive.
Your doctor may want to treat it with:
- Chemotherapy
- Different EGFR inhibitors
- Immunotherapy
Treating Later-Stage Lung Cancer
Treatment for late stage III and stage IV EGFR-positive lung cancer depends largely on your EGFR mutation.
You'll work with your doctor to create a cancer treatment plan that works best for you.
Exon 19 deletions and exon 21 L858R point mutations
There are three main options for these mutations:
- Osimertinib or another EGFR inhibitor. You can get this treatment alone.
- Osimertinib with chemotherapy. Often the preferred treatment because research suggests there's a better survival rate. One study, known as the LAURA study, found that patients who got chemoradiation plus osimertinib for three years lived for around 39 months, compared to five and a half months for those who did not get it.
- Lazertinib (Lazcluze) combined with amivantamab-vmjw (Rybrevant). Lazertinib is another EGFR inhibitor combined with amivantamab that showed eight months more progression-free survival compared to just using one EGFR inhibitor.
The good news is that newer EGFR inhibitor treatments can more easily cross the blood brain barrier.
That includes medicines like osimertinib and lazertinib plus amivantamab. And this means the meds work better to treat brain metastasis.
S7681, L861Q, or G719X mutations
Afatinib (Gilotrif) is the standard treatment for lung cancers that don't respond to EGFR inhibitors. Your doctor may also add chemotherapy or targeted therapy, too.
Exon 20 insertions
Standard treatment uses amivantamab along with chemotherapy. If that doesn't work, then you may get sunvozertinib (Zegfrovy). But this medicine is very new.
Sunvozertinib isn't widely available yet, but we expect it will be used more frequently in the future.
Sunvozertinib isn't widely available yet, but we expect it will be used more frequently in the future.
How to Make Non-Small-Cell Lung Cancer Treatment Goals
When Toni Enright, 69, was diagnosed with stage IV NSCLC in 2016, she was completely overwhelmed.
"The first oncologist I met with told me my only option was chemotherapy," says Enright, who lives in Los Angeles. "I walked out of his office and just felt so bleak."
Thankfully, Enright's college-age daughter had a friend whose mother worked for a lung specialist at Cleveland Clinic.
Get tested for mutations
"We were able to get in touch with him, and he stressed how important it was to get my biopsy tissue tested for mutations," recalls Enright.
She did and learned that she had an EGFR-positive mutation. "It opened up a whole new treatment pathway since there were targeted therapies available," she says.
Know Your Diagnosis
You're an important part of your lung cancer treatment care team.
Enright says that if she hadn't called her doctor's office numerous times to insist her tissue be tested, it wouldn't have happened.
Get the right treatment
"I was scheduled to start chemotherapy on a Tuesday, and that Monday night, he finally called me to tell me I had the EGFR-positive mutation and that there were targeted drugs available to treat it," she says.
She ended up going on erlotinib, which she remained on until 2022, when she switched to osimertinib after her cancer began to advance again.
Take your treatment as prescribed
Research suggests that about a quarter of all lung cancer patients don't always follow their treatment plans, including taking medications as prescribed.
Newer medications such as osimertinib tend to have fewer side effects. And this can make it easier for you to stick to your treatment plan.
But if side effects make it hard to take your meds, talk to your cancer care team. They may be able to prescribe medications to help manage any unwanted effects.
Quality of life matters
If it's hard for you to keep up with your treatment plan, speak to your doctor.
Creel delayed her initial chemotherapy after her November 2024 diagnosis to January of 2025.
"I worried that if I started treatment in December, it would interfere with my spending time with my children around the holidays," she says. Her doctor agreed and cleared her to start a month later.
Today, while she is on chemotherapy, she goes once a month instead of once every three weeks.
"I talked it over and weighed the pros and cons with my doctor," she says. "Chemotherapy really knocks me out, and it felt like it affected my quality of life too much to go more than once a month."
Prevent and manage cancer spreading to your brain
Both Creel and Enright had signs of brain metastasis when they were diagnosed with lung cancer — and both saw improvement once they began treatment.
It is important to watch yourself carefully for signs of brain metastasis when you have lung cancer. Symptoms include:
- Memory problems
- Trouble with balance
- Personality changes
- Seizure
More rarely, brain metastasis can lead to swelling and bleeding in the brain.
Every patient with EGFR-positive lung cancer should get a neurologist on their team, especially if they have or have had brain metastasis.
Get a second opinion
Even if you like your doctor and feel confident about treatment, it's always a good idea to check with another specialist.
"When I was diagnosed, my original oncologist told me I wasn't a candidate for surgery since I had stage IV cancer," says Creel.
She decided to seek out a second opinion with Heymach at MD Anderson Cancer Center, who suggested it. She had an operation to remove what remained of her cancer in June 2025, and since then, it has gone into full remission.
Questions to ask your doctor about EGFR-positive NSCLC
- What type of EGFR mutation do I have?
- Does my cancer have any other biomarkers?
- How many patients do you treat who have EGFR-positive lung cancer? If needed, can you recommend someone who has more experience?
- What are the treatment options for my type of EGFR-positive lung cancer?
- Are there clinical trials for my type of EGFR-positive lung cancer that I would be a good candidate for?
- What is the goal of treatment at this point?
- What are the chances of treatment working to meet this goal?
- What are the side effects or risks of treatment? How can I lessen them?
- What can we do if my treatment stops working?
- What follow-up tests will I have to see if treatment is working?
- Will I need to have biomarker testing again?
Outlook for EGFR-Positive NSCLC Is Improving
Having EGFR-positive lung cancer can be challenging, but newer targeted treatments offer hope.
Many recent targeted therapies not only extend life but can improve the quality of it, too.
It's the poster child for our treatment of lung cancer.
When patients respond, they respond beautifully to the newer medicines we have available.
In the meantime, researchers are working hard to create new medicines for metastatic cancer and for those cancers that don't respond to current treatments.
If your cancer isn't responding to treatment, ask your doctor if you are a candidate for any clinical trials for EGFR-positive lung cancer.
Where to find clinical trials
You can also find a list of clinical trials at ClinicalTrials.gov.