Ask the Expert: What’s the Future of EGFR-Positive NSCLC Treatment?

Early-stage EGFR-mutant NSCLC can potentially be cured with surgery or radiation therapy, either with or without chemotherapy.

Therapies specifically targeting the EGFR mutation can help stop or slow the progression of the disease after a person has surgery, but it’s not yet known whether those therapies improve a person’s overall survival or the likelihood that their lung cancer can be cured.

Advanced or metastatic EGFR-mutant NSCLC isn’t yet considered curable. However, many patients can have a long response (sometimes for multiple years) with EGFR-targeted therapy, though they typically become resistant to it eventually.

These targeted therapies are considered to be quite different from conventional chemotherapy, usually with fewer side effects.

Osimertinib has largely replaced earlier generation targeted therapies, like erlotinib, gefitinib, and afatanib, as the first-line treatment for advanced EGFR-mutant disease. The medication targets the EGFR protein and blocks its activity.

Compared to the other therapies, osimertinib leads to longer overall survival and more time spent without disease progression. Half of patients on this drug can have their disease controlled for over 1.5 years, and many others have even better outcomes. It also comes with fewer side effects than other therapies.

Osimertinib can also be useful for certain patients whose disease continued to progress when taking the earlier-generation targeted therapies.

There may continue to be improvements in future generations of EGFR-targeted therapy.

Researchers are also investigating other targeted therapies for less common types of EGFR mutations, such as the exon 20 insertion mutation.

Newer combinations of immunotherapy and chemotherapy are being studied for patients who’ve had recurrences after targeted therapy.

Furthermore, localized radiation therapy or surgery for tumors that have continued to grow are showing promise at making targeted therapy more effective and durable. These treatments may also help a person avoid the need to switch from targeted therapy to a different type of medication.

EGFR, or epidermal growth factor receptor, is a protein that can cause tumors to grow if it becomes mutated. That can lead to a type of enzymes called tyrosine kinases to cause unregulated growth, which can lead to cancer and cause it to spread.

Targeted tyrosine kinase inhibitors (TKIs) like osimertinib can block these out-of-control tyrosine kinases and help control EGFR-mutated NSCLC.

When lung tumors harbor this specific mutation, they may respond favorably to these targeted therapies with generally less severe side effects than more conventional chemotherapy.

Most of the time, EGFR-mutant NSCLC isn’t hereditary. However, there are some rare reports of inherited lung cancer syndromes, especially in patients who didn’t have a history of cigarette smoking.

EGFR-positive NSCLC is more common in people who are nonsmokers, women, and people of Asian ancestry, though most of the time it’s not carried down through families.

EGFR mutations are found in about 15 percent of people with lung cancer in the United States, according to the advocacy group EGFR Resisters.

That rate is higher among people of East Asian descent, accounting for 35 to 50 percent of their lung cancer cases.

If you’re currently smoking cigarettes, this would be a good time to consider cutting back or stopping altogether. It may be helpful to ask your oncology team or primary care office to support you in this endeavor.

Otherwise, maintaining as healthy of a lifestyle as possible regarding diet and regular exercise is ideal. Dietitians and physical therapists can help you develop a personalized lifestyle regimen that would be healthy and realistic for your situation.

Henry S. Park, MD, MPH, is a thoracic radiation oncologist with Yale Medicine’s Department of Therapeutic Radiology who cares for patients at Yale Cancer Center and Smilow Cancer Hospital.

Dr. Park specializes in advanced radiation techniques like stereotactic radiosurgery, stereotactic body radiation therapy, image-guided radiation therapy, and intensity-modulated radiation therapy to treat patients.

Also an assistant professor of therapeutic radiology and the chief of thoracic radiotherapy at Yale School of Medicine, he is passionate about being involved in research that may lead to further improvements in cancer care and survival.