Case Overview: EGFR-Positive NSCLC

Sarah Goldberg, MD:This is a woman who’s a fairly young woman of Chinese descent who is a never-smoker, and she has fairly recent onset of pulmonary symptoms—cough, chest pain—and has had several years of recurrent bronchitis. But because of her new symptoms, she went to her doctor and underwent a chest CT where she was found to have a lung mass as well as pleural disease. And she had a biopsy that showed lung adenocarcinoma. A mutation testing was done and it showed anEGFRmutation. What was interesting about that mutation is that it was an uncommon mutation. It was aG719Xmutation. It was also negative forALKas well asKRAS.

Because this woman was a never-smoker, one might think that she’s not at risk for lung cancer. But there are patients who have never smoked or have smoked a very small amount in the past who can get lung cancer. Much more commonly, patients who have smoked are at greater risk of lung cancer. But such as this woman, there are patients who have never smoked who can get lung cancer, and mutations such asEGFRare more common in patients who have never smoked.

As I mentioned, what’s interesting about this case is that she does have a rare mutation inEGFR, theG719mutation. And so, this mutation, while it is uncommon, we do sometimes see it in lung cancer. And it does lead to a sensitivity of the EGFR inhibitor, so it is very important to note that that is present in her cancer. And so, her cancer may have been able to be caught at an earlier stage if imaging was done earlier.

What’s challenging in patients like this is that they don’t commonly undergo imaging because if they have bronchitis or they have pulmonary symptoms, lung cancer is not usually on the forefront of doctors’ minds, or a patient’s mind, because they’ve never smoked. So it’s not thought to be a possibility in patients like this, and actually that’s probably for a good reason because lung cancer is not common in never-smokers. So, lung cancer screening can be done in patients, but again, not typically in patients who are never-smokers because of the very low risk in those patients.

Recommendations for lung cancer screening currently are patients who are between the ages of 55 and 80 who have a history of smoking 30 pack years or greater and either are current smokers or have quit in the last 15 years. So, those are patients who are at the greatest risk of having a lung cancer, and that’s why they’re included in the recommendations. There was a trial that looked at patients who fell into that group, and those patients were screened using a low-dose CT scan looking for abnormalities. And it was found that if you did a low-dose CT scan that you could find abnormalities that then potentially could lead to the diagnosis of lung cancer and decrease the risk of lung cancer death. And so, that now is the recommendation to screen patients with those factors. So, you can see that this patient would not have fallen into that; she had no history of smoking at all. And so, that’s why she did not get a lung screening and she only underwent a CAT scan once she developed symptoms.

Transcript edited for clarity.

• A female patient, Chinese descent, aged 66, is referred from primary care with persistent cough, sputum with blood, shortness of breath and chest pain
• History
  • Never smoked
  • Recurrent bronchitis over past 5 years
  • Has never been screened for lung cancer (by radiography or low-dose CT [LDCT])
  • Hypertension controlled on HCTZ; no diabetes, renal impairment
  • Family history
    • Grew up in China, moved to US at age 29; married for 30 years
    • Grew up in family with heavy smokers
    • Husband is current smoker
• LDCT reveals multiple tumors in left lung with pleural metastases
• Biopsy reveals non-small cell lung cancer
• Molecular analysis:
  • EGFRmutation: G719X
  • Negative forALKrearrangement
  • Wild-typeKRAS
• The patient was started on afatinib, 40 mg once daily
• After one month on therapy, she reported having rather severe diarrhea (5 times/day)
• Treatment was discontinued, then re-started treatment at 30 mg/day