EGFR Mutations in NSCLC

Corey J. Langer, MD:EGFRmutations are present in about 10% to 15% of the newly diagnosed non—small cell North American population. If we look at East Asia, specifically at a person of East Asian ethnicity, who is a never-smoker female with adenocarcinoma, the likelihood of having anEGFRmutation goes up to 60% to 65%. So, it’s imperative, in the modern era of personalized medicine, specifically personalized oncology, that we work up our patients forEGFR.

In my own clinic, I would guesstimate that I have at least 60 or 70 patients withEGFRmutations. The vast majority are doing quite well. They’re on a variety of tyrosine kinase inhibitors (what we call TKIs). Some of them are on TKIs for several years. In fact, one of my patients who was on one of the original gefitinib trials remains on the agent—now going on a decade and a half. So, 15 to 16 years with metastatic lung cancer to bone.

This population does far better than the general non—small cell lung cancer population. If we look at older studies, on average, their median survival is 2.5 to 3 years. With more modern treatment, I’d venture to guess that we’re doing even better than that. Many of these patients are living 4, 5, or 6 years or longer.

Of all the actionable mutations that exist,EGFRis the most common. It is not the most common mutation, however.KRASmutations are found in 25% to 35% of newly diagnosed non—small cell, nonsquamous patients. Unfortunately, we don’t yet have a drug or a TKI for that group.KRASis much more commonly seen in smokers or former smokers, whereasEGFRmutations are typically seen in never-smokers or remote former smokers. My rule of thumb, regarding the workup forEGFR, is to test all patients with adenocarcinoma, regardless of smoking history, and all never-smokers or remote former smokers, regardless of histology.

Transcript edited for clarity.

June 2017

• A 61-year-old Caucasian woman presented with persistent cough and shortness of breath
• Patient history:
  • Never smoked
  • Mild hypertension, controlled on diuretic
  • No major cardiovascular disease or diabetes
  • Worked at local jazz club until symptoms forced her to resign
• Physical exam and imaging:
  • No palpable masses
  • CT reveals multiple tumors in right lung and brain metastases
  • ECOG PS: 1
• Biopsy and mutation analysis:
  • Adenocarcinoma
  • EGFRexon 19 deletion
  • No ALK rearrangement
• Started treatment with afatinib 40 mg once daily
  • Developed diarrhea that necessitated dose interruption
  • Recovered and resumed treatment at 30 mg once daily

March 2018

• Patient remains on afatinib, with no apparent progression