A Case of EGFR Exon 20 Insertion–Positive NSCLC


A case of a 64-year-old man with non–small cell lung cancer, who tested positive for an EGFR exon 20 insertion mutation after progression on frontline therapy.


Joel Neal, MD, PhD: Hi, I’m Joel Neal from Stanford University. It’s my pleasure today to present a case of a patient with EGFR exon 20 insertion–mutated non–small cell lung cancer. We’ll start with the case and then we’ll go into some questions about it. Hypothetically, let’s say that this case was coming from one of my referring oncologists here in Northern California, and they were wondering what to do next for second-line treatment.

This is a 64-year-old man who presented to his primary care physician [PCP] and was complaining of shoulder pain on the left side and a dry cough over the last few months. He spends most of his days working in his garage puttering around, but lately, he says he feels tired after just an hour, instead of being able to go all day long, and he’s lost close to 8 lb over the last 4 months. This was unintentional weight loss without any changes in his eating habits.

His past medical history, as typical for many people in the United States, is hypertension [and] hypercholesterolemia. He did have a distant smoking history, 5 pack years, but quit about 30 years ago when he was around age 35. Occasionally, he has a beer with his friends on the weekends. He lives with his wife and his son and has no family history of cancer. On [the] physical examination, his primary care physician found that he had [a] left lower lobe with decreased breath sounds, but otherwise unremarkable.

Laboratory tests were done in the clinic. A CBC [complete blood count] panel was normal, and comprehensive metabolic panels were normal, including normal liver and kidney function. A CT scan of the chest was done by his PCP, which demonstrated a 3.5-cm left lower lobe mass, left effusion on the side, mediastinal lymph nodes, and a lytic area in the left scapula, as well as a question of some lytic areas in the vertebrae.

He was referred to [a] biopsy with a pulmonologist, who did an endobronchial ultrasound of the mediastinal nodes, and this demonstrated non–small cell lung cancer, TTF-1 [thyroid transcription factor 1]–positive adenocarcinoma. He got a PET [positron emission tomography] CT and was referred to a medical oncologist in our community. This demonstrated multiple bone metastases that were FDG [fluorodeoxyglucose] avid, including in the vertebrae and the left scapula. A brain MRI was performed, which demonstrated a 1.5-mm enhancing lesion, and this was called on the report to be potentially a metastasis versus a vessel, but too small to fully characterize. Further testing on the tissue demonstrated [a] PD-L1 test of 75% positive, and the referring oncologist sent out tissue for molecular testing by DNA next-generation sequencing. With this particular provider, it was about a 3-week turnaround.

The patient was started on chemotherapy after a discussion. This patient and provider decided to start cisplatin and pemetrexed. This worked for an initial 4 months. And during that time after initial response, the bone metastases became more sclerotic than lytic, but unfortunately, the primary tumor progressed, and there were new bone metastases after about 4 to 5 months of treatment. During this time, the next-generation sequencing came back from the tumor tissue and demonstrated an EGFR mutation. But interestingly, this EGFR mutation was not the typical sensitizing mutation to EGFR TKIs [tyrosine kinase inhibitors], but instead was an EGFR exon 20 insertion mutation, considered resistant to the first-generation EGFR TKIs.

Then the patient was referred to us at Stanford [University] for consideration of next-line therapy and to consider all of the available options.

Transcript edited for clarity.

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