Consumer’s Guide to Targeted Therapies for EGFR+ Non-Small Cell Lung Cancer

Several targeted therapies have been approved by the U.S. Food and Drug Administration for the treatment of specific EGFR mutations in NSCLC. They’re broken down into two categories:

Tyrosine kinase inhibitors (TKI):

• afatinib (Gilotrif)
• erlotinib (Tarceva)
• gefitinib (Iressa)
• osimertinib (Tagrisso)
• dacomitinib (Vizimpro)

Monoclonal antibodies:

• amivantamab-vmjw (Rybrevant)

“Osimertinib is currently the standard of care and first-line treatment for EGFR-mutated NSCLC in the metastatic setting, meaning the cancer has spread beyond the lungs,” says Heather Katz, DO, an oncologist at Phelps Memorial Hospital in Sleepy Hollow, New York, and an assistant professor of medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in Long Island. It’s also approved for use in people who have had NSCLC tumors surgically removed.

Other options, such as amivantamab-vmjw, aim to treat mutations, such as the exon 20 mutation, that are resistant to other targeted drugs.

Previously, only people with stage IV (advanced) disease were checked for EGFR-positive lung cancer, according to Dr. Katz. 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 radiation and chemotherapy. Since it means the cancer has spread beyond the lungs, later-stage 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.

When the cells in your body think they’re supposed to continuously grow, that growth can get out of control, 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 [in] ‘on.’”

The purpose of targeted treatments in EGFR-positive NSCLC is straightforward: to turn off the cell signaling in the EGFR gene, which reduces the number of cancer cells in the body, says Katz.

Over 70 EGFR mutations have been identified. They’re classified by which exon is altered. Exons are a segment of DNA coding that contains information for a protein sequence. So far, treatments have been developed for mutations affecting exons 18, 19, 20, and 21.

When people think of genetic mutations, many assume they’re passed down through families. While the risk for some types of cancer can be inherited, EGFR mutations don’t fall into that category. Instead, they occur randomly. In the case of EGFR, “There’s something that was a spontaneous mutation in the tumor,” Eaton says.

All of the TKIs are taken in pill form, 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.

On the other hand, the monoclonal antibody, amivantamab-vmjw, is administered by IV — weekly for the first four weeks of treatment and then every two weeks thereafter — usually in an infusion clinic.

EGFR is also present in healthy cells, including the skin, according to Jack Jacoub, MD, an oncologist and the medical director of MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, California. As a result, targeted treatments for EGFR-positive NSCLC can cause a skin rash. Another common side effect is diarrhea. Fortunately, these symptoms are easy to treat and probably won’t require stopping cancer 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 rarer side effect is lung inflammation. When that happens, it’s necessary to stop cancer treatment, he adds.

EGFR-targeted treatments can cost up to $15,000 a month, Eaton says. “But also, most insurance covers it,” he adds. “Sometimes there is a high copay, and many times patients with that high copay will qualify for patient assistance.” The manufacturer of each medication offers a patient assistance program, which you can research on the drug’s website.

Although late-stage lung cancer generally can’t be cured, targeted treatments have been shown to extend life, compared with not taking them. “On average, people are living a year and a half to two years on these drugs,” says Jacoub. “That’s an average, but there’s a good percentage of patients that live longer.” The treatments also help keep cancer symptoms from progressing, so you can have a better quality of life during that time, too.