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

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:

TKIs:

• afatinib (Gilotrif)
• erlotinib (Tarceva)
• gefitinib (Iressa)
• mobocertinib (Exkivity)
• osimertinib (Tagrisso)

Monoclonal antibodies:

• 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.

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.

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.

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.

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.

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.

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.

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.

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.