Finding out you have epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) is a shock for anyone. You’ll have a lot to process and learn about your cancer and how your life is about to change. Having as much information as possible can help you feel empowered. It can help you better understand your treatment options and what to expect over time.
You might ask: What is EGFR-mutated NSCLC, anyway? How is it different from other lung cancers? And, what does it all really mean for me?
Difference #1: Your Cancer’s Biology
NSCLC is the most common form of lung cancer. About 8 out of every 10 lung cancer cases fall into one subtype or another of NSCLC. Most EGFR-positive lung cancers are NSCLC adenocarcinomas, which means they start in cells lining your lungs that make mucus.
EGFR is short for epidermal growth factor receptor. It’s a protein receptor that sits on the surfaces of cells in various parts of your body, including your skin and lungs. Knowing that your NSCLC carries an EGFR mutation, or it is EGFR-positive, tells you a lot about your cancer and what’s making it grow.
Normally, EGFR helps cells multiply and grow in healthy ways. For example, it can help your skin or lungs heal if they’re damaged. In EGFR-mutated NSCLC, the EGFR gene and the protein it makes have a change that makes the protein work differently. Christine Bestvina, MD, a lung cancer specialist at the University of Chicago Medicine in Illinois, says identifying mutations such as EGFR through molecular testing is important for understanding what’s driving your cancer.
“When a tumor has an EGFR mutation that is considered a driver mutation, and so acquiring that change in the DNA of the cancer cells…is thought to be what makes the cells grow at a faster level,” Bestvina says. “It’s also what potentially drives those cells to spread to other areas [in your body].”
EGFR isn’t the only driver mutation that’s commonly found and tested for in NSCLCs. It’s possible to have more than one driver mutation at the same time or for your cancer’s mutation status to change over time. Some lung cancers happen without any clear driver mutation, too.
It may seem complicated. But the good news is that knowing early on that your cancer has this key genetic difference can help you and your doctor better understand and treat it.
Difference #2: Who Gets It
“This is a significant portion of non-small-cell lung cancer, especially in Asia,” says Pasi Jänne, MD, a medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts. “In the U.S. and European Union, about 15%-20% of patients diagnosed with non-small-cell lung cancer will have EGFR-mutant lung cancer. In Southeast Asia, it’s about 50%, so it represents a much larger population of individuals there.”
Ethnicity
Studies have shown that Asian people with newly diagnosed lung adenocarcinoma carry EGFR mutations more than half the time. The frequency varies depending on which country you’re from or your ethnicity. For example, EGFR mutations are especially common in people with NSCLC from:
- Vietnam
- Thailand
- China
- The Philippines
By comparison, the frequency of EGFR mutations in people from India with lung cancer is lower, at about 20%. Even though EGFR mutations turn up more often in people from Asia with NSCLC, people from Asia get lung cancer less often compared to other groups for reasons that aren’t entirely clear.
Gender
Women or people assigned female at birth (AFAB) with NSCLC more often have EGFR mutations compared to men. Women also get diagnosed more often at younger ages. This might be explained by the differences in estrogen hormone levels.
For example, there’s evidence that lung tumors often have an unusual number of estrogen receptors on them. As a result, researchers are exploring whether estrogen blockers might improve outcomes for women with EGFR-positive lung cancer.
Age
Lung cancer is most often diagnosed in older people. But EGFR-positive lung cancer is more often diagnosed at younger ages compared to other forms of lung cancer. That’s because it’s driven by the EGFR mutation. It doesn’t take years of smoking or other environmental exposures to cause the cancer.
Combined risk factors
Because EGFR-positive lung cancer is more common among young people, never-smokers, women, and Asian people, it is especially common in people who fall into more than one of these categories. For example, one study of East Asian women with lung cancer who’d never smoked found 63% had an EGFR mutation.
Anyone can get it
Bestvina says it’s important to remember that people of any age or ethnicity can get EGFR-positive NSCLC. That’s why all patients with NSCLC should have their tumor tested for EGFR and other molecular biomarkers.
“The profile that we historically have thought about is a patient who may be younger, a patient who may be a never-smoker or had only a very light smoking history,” Bestvina says. “But part of what we’re trying to change right now is that narrative. All patients with non-small-cell lung cancer should have molecular testing done on their tumor because it’s not just young, never-smokers who get EGFR-mutated lung cancer.”
Difference #3: It’s Not Tied to Smoking
About 80% of people who get lung cancer have smoked at some point in their lives. The link between lung cancer and smoking is the reason the disease often comes with a stigma. But many people with EGFR-mutated lung cancer get this disease even though they have never smoked or have hardly smoked.
The reason is that your disease is being driven by underlying changes in the EGFR gene that cause your cells to grow in an uncontrolled way. This happens regardless of your smoking history. This feature of EGFR-mutated lung cancer can make it especially puzzling and hard to accept a new diagnosis, says Trever Bivona, MD, a medical oncologist at the University of California San Francisco (UCSF) Health. You might feel angry, or you may feel it’s not fair.
“[When] someone has never smoked and they have lung cancer at age 50, that comes with a shock,” Bivona says. “But lung cancer, especially EGFR, is a disease of mutations. I think that dispelling the myth that if you have lung cancer, you did something bad — whether or not you smoked — is important for patients.”
Difference #4: Your Treatment Options
Your treatment for EGFR-mutated lung cancer may depend on your cancer’s stage and whether it can be removed with surgery. Each person and their treatment is unique. But knowing your cancer carries a mutation in EGFR means you’re more likely to benefit from targeted therapy. Targeted therapies for EGFR-positive cancer are designed specifically to block EGFRs. They’re also called EGFR inhibitors.
EGFR inhibitors approved for EGFR-mutated NSCLC include:
- Afatinib (Gilotrif)
- Amivantamab (Rybrevant)
- Dacomitinib (Vizimpro)
- Erlotinib (Tarceva)
- Lazertinib (Lazcluze)
- Osimertinib (Tagrisso)
- Sunvozertinib (Zegfrovy)
You might take targeted medicine alone. Or you might take it with chemotherapy or other agents in combination. The best option for you may depend on which specific EGFR mutation you have, your cancer stage, and other factors. Be sure to talk to your doctor about your treatment goals and the pros and cons of each option.
Researchers are also working on new treatment options that may work better or may work after your cancer becomes resistant to an EGFR inhibitor. Consider asking your care team about clinical trials testing new treatment candidates or combinations, which will expand your options even more. You can search for open trials in EGFR-mutated NSCLC near you at clinicaltrials.gov.
Difference #5: Your Survival Outlook
Your many treatment options and their specificity mean that you’ll have a better prognosis with an EGFR-mutated NSCLC diagnosis today than ever before. Your prognosis with EGFR-mutated lung cancer is generally better than it would be if your cancer didn’t have a clear treatment target.
“Because of the breadth of options we have for these patients, the prognosis is often much better than [that for] a patient without an EGFR mutation,” Bestvina says. “We have new and exciting therapeutic options that will specifically target that mutation.”
About 30% of people diagnosed with lung cancer live at least five years, according to the latest statistics. Your outlook will depend on your cancer stage. Overall, about 10% of people with advanced lung cancer live five years compared to 65% of people with early stage, localized lung cancer.
By comparison, the outlook for EGFR-mutated cancer is often better. For example, a clinical trial showed 40% of people with EGFR-mutated lung cancer that had spread to their brain or spinal cord lived at least three years with an EGFR inhibitor alone. By combining the EGFR inhibitor with chemotherapy, the three-year overall survival increased to 57%. Your odds with newer targeted medicines may be even better.
Remember that survival statistics can’t predict your future. With treatment advances now underway, Bestvina says you can expect for outlooks with EGFR-mutated lung cancer to keep improving.
Where to Find Community and Support
You should know you aren’t alone. While friends and family are essential for support, it can help to reach out to others who have EGFR-mutated NSCLC in your community or via online support groups and know exactly what it’s like. Bestvina says the EGFR Resisters is a good place to start.
“There’s a very strong community of patients living with EGFR-mutated lung cancer,” Bestvina says. “If you’re looking for support, or just looking to talk with others who are having a shared experience, I think that can be an extremely important asset for this group of patients.”
