ONCAlert | 2018 Gastrointestinal Cancers Symposium
Lung Cancer Case Studies

Molecular Testing for NSCLC

Roy S. Herbst, MD, PhD
Published Online:May 30, 2017
In this case-based interview, Roy Herbst, MD, PhD, discusses the treatment of a patient who develops EGFR mutant non-small cell lung cancer.

Treatment of EGFR Mutant Non-Small Cell Lung Cancer

Roy S. Herbst, MD, PhD: For non–small cell lung cancer, the diagnostic workup is really well-described here. One would, of course, want to get an x-ray of the chest, but clearly a full metastatic workup is important. One can do that with a CT scan or a PET scan. And then, it’s always important to know if there is CNS involvement or not. In many cases, that might necessitate treatment with radiation first. Mutational testing and profiling are critical these days.
At our center, the Yale Cancer Center, for everyone with new lung cancer that comes in, we’re sending their tumors for profiling, which includes the EGFR, ALK, and ROS1 mutations. We also test those patients for PD-L1. So, that is all critical. Then, of course, there’s no substitute for seeing the patient and evaluating them and their performance status in person, perhaps on multiple occasions, which has been done for this man as well.
In 2017, most patients will have molecular testing on their tumor. In fact, I think it should be a standard of care for all non–small cell lung cancer cases. That would include EGFR, ALK, ROS1, and, I believe, PD-L1 testing. This all really should be done in fewer than 10 days. Those would be the College of American Pathologists guidelines. We try to do that.
I think it’s important, because you don’t want to start your frontline therapy until you’ve ruled these things in or out, because it does affect whether or not you would give the patient immunotherapy, an oral targeted agent, or standard chemotherapy. I see this happening more and more across the United States. Uptake has been high, but it’s taken some time, and I worry that it’s not available in all areas—and certainly not around the world. But, in the United States, this is what I would consider the new standard of care, and there are more and more places where this testing can be sent out to be done.
Molecular testing is critical for the use of EGFR upfront therapy. You wouldn’t use it unless someone had a mutation. The 2 most common mutations—and the ones that have been shown to respond, typically, to the oral EGFR agents—are either exon 19, which tends to be a deletion mutation, or exon 21, which tends to be a point mutation. Both are what we would consider the canonical EGFR mutations, with 60% to 70% response rates to erlotinib, gefitinib, or afatinib, the three approved agents in the United States.
If one were to have a mutation in a different area, it still could respond, but the chances of that are much less. So, we would call that an atypical non-canonical mutation. One thing that has been shown in a number of studies is that the results are a little bit better for the exon 19 deletion mutation versus the exon 21 point mutation. It’s a more significant mutation, but all of these mutations are ones that should be treated right away with an oral EGFR therapy.

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.
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