A Case of EGFR-Mutant NSCLC

Roy S. Herbst, MD, PhD:This is the case of a patient with metastatic non—small cell lung cancer. The patient presents with symptoms and a diminished performance status—performance status 2. And, as you would expect, there’s evidence of lung cancer to metastatic sites: a 4 cm lesion in the lung, but also bone metastases and some lymph node involvement. So, this patient has stage 4 disease. That’s the first thing that’s critical in making an assessment. The second is that the patient is a former smoker but hasn’t smoked in 12+ years, so there is still a chance that the patient could have an actionable mutation. Then the question is, how do you treat? It is significant that the brain tested negative for lesions, so that’s normal on an MRI scan. That’s the basic assessment of this patient, and the question: What to do next?

The other critical point here is that we’re told the patient has anEGFRmutation—anexon 19deletion mutation. That’s very important, because here you have somebody with a PS of 2, and without seeing them, they might be very worried about chemotherapy. One could consider immunotherapy these days if a patient was high in PD-L1, but here we have someone who’sEGFR-mutated in exon 19. That’s a canonical mutation. The chance of response to an EGFR inhibitor should be 60% or 70%, so that begins to lead us down a very specific path of treatment.

This patient has stage 4 non—small cell lung cancer, and that is an incurable disease even in this era of EGFR inhibitors. However, it’s very treatable in my opinion, even with a performance status of 2—especially since this performance status is probably due to the bony disease and the metastases of the cancer. So, if this patient can actually get therapy with an EGFR inhibitor or an oral agent and responds, my prediction would be that he would feel a lot better. While I wouldn’t call this curable disease— because, even if the patient responds to the EGFR inhibitor, there’s a chance of resistance, and then we would move to a second-line agent and so forth—I think that the short-term goals are quite optimistic ones. I would tell the patient, “You’re quite lucky. You have an actionable mutation. Let’s take action right away.”

Transcript edited for clarity.

• 65-year-old male, former smoker (25 pack-years, quit 12 years ago) presented complaining of persistent lower back pain, extreme fatigue, shortness of breath, and a 25-lb weight loss in the past 6 months.
• PMH includes rheumatoid arthritis which significantly limits his physical activity.
• Back pain also limited the patient’s daily activity.
• MRI of the spine showed evidence of multiple lesions, but none were causing cord compression.
• CT of the chest showed a 4-cm mass in the left lung, with enlarged bilateral mediastinal lymph nodes.
• The MRI of the brain revealed no metastases.
• ECOG PS was assessed to be 2.
• He underwent an endobronchial ultrasound-directed biopsy of the mediastinal lymph nodes.
• Pathology revealed poorly differentiated adenocarcinoma.
• Molecular testing showed a mutation in EGFR exon19 deletion.