Next-Generation Sequencing Is ‘Treatment Changing’ for Cancer — But What Is It?

Next-generation sequencing (NGS) is a test that can be done in patients with non-small cell lung cancer (NSCLC) and that identifies mutations in the cancer; this can then drive treatment decisions. One expert said all patients should be advocating for undergoing NGS testing, regardless of disease staging.

“It’s important for patients to be educated on this, because the more we know about a patient’s cancer, the better we can design a personalized treatment plan. Not all lung cancers are alike, and with the help of biomarkers we have been able to help patients with lung cancer live longer,” said Dr. Melinda Hsu.

Hsu, assistant professor of hematology and oncology at the University Hospitals Seidman Cancer Center in Avon, Ohio, discussed NGS testing for the EGFR exon 20 alteration mutation and what it means for patients during an interview with CURE®.

CURE®: What is NGS testing? What can it tell us, about the EGFR exon 20 alteration?

Hsu: NGS … is a way to assess for the presence of clinically relevant biomarkers by sequencing DNA of the cancer. NGS is done in different ways and usually is performed on a sample of the cancer tissue. In patients with lung cancer, NGS testing can identify the presence of a targetable gene alteration driving growth of the cancer. There are targeted drugs, mostly pills, which have been developed specifically for some of these biomarkers for patients with (NSCLC). The EGFR exon 20 insertion mutation is one of those biomarkers. When NGS testing identifies this biomarker, it can help determine treatment options for a patient with lung cancer depending on the stage of their disease. There are … several alterations of the EGFR gene (that) seem to drive the growth of NSCLC and using NGS testing to confirm which specific mutation is present is treatment changing.

Which patients should be tested for this alteration?

I believe that all patients with NSCLC should have NGS testing, regardless of the stage of their disease. Patients with lung cancer who never smoked or did not smoke much, are more likely to have a targetable biomarker like the EGFR exon 20 alteration, but that should not preclude testing. Right now, the two Food and Drug Administration (FDA)-approved drugs specifically (targeting) EGFR exon 20 are only available for patients with metastatic, or stage 4, lung cancer in the second-line setting (after the patient has progressed or not responded to standard-of-care first-line treatment of platinum-based chemotherapy with or without immunotherapy).

However, I believe that patients with earlier-stage lung cancer should also have NGS testing done of their tumor, for prognostic information and because the use of targetable drugs is moving into the adjuvant setting (for example, the use of Tagrisso [osimertinib] in patients with EGFR exon 19 or 21 alterations after surgery). And unfortunately, the recurrence of rate of localized or locally advanced NSCLC is still high and having the NGS testing up front can guide treatment decisions if the cancer recurs.

How can NGS testing for this alteration be beneficial to patients? Can it help guide treatment decisions or prognosis?

NGS testing for the EGFR exon 20 alteration guides prognosis and treatment decisions for patients with metastatic NSCLC. Unfortunately, patients with metastatic EGFR exon 20 altered-NSCLC have historically had a poorer prognosis than others when treated with chemotherapy. If their cancer does not respond to first-line standard of care treatment, however, there are two drugs, Exkivity (mobocertinib; a pill) and Rybrevant (amivantamab-vmjw; an infusion), which are now FDA approved. Knowing about an EGFR exon 20 alteration through NGS at the time of diagnosis gives hope to our patients that there is another option for treatment if standard of care doesn’t work or stops working and can also expedite treatment at progression rather than waiting for NGS testing to be done then.

Should patients be advocating for themselves to have NGS testing for this alteration? How can they do that?

Patients should absolutely advocate to have NGS testing done, for this biomarker and the other biomarkers found in lung cancer for which we have targeted therapies. Patients should ask their oncologist (whether) NGS has been done on their cancer tissue when they meet them or confirm that it will be done on their biopsy if not yet done. Here at Seidman Cancer Center, we have reflex (automatic) NGS testing done for the most common lung biomarkers on all of our patients’ pathology found to be NSCLC, so our patients don’t even need to ask for it. Hopefully someday that will be possible for all patients with lung cancer.

Are there any current gaps or limitations in this space?

Sometimes there is not enough tissue from a biopsy for NGS testing. When that happens, it may be possible to do a liquid biopsy, or a blood draw, to try and identify any biomarkers. Liquid biopsies rely on the aggregate presence of circulating tumor DNA in the bloodstream for NGS testing. Unfortunately, if the liquid biopsy is negative on NGS testing, that does not absolutely rule out the presence of a targetable biomarker as liquid biopsy testing is less sensitive than that performed on tumor tissue. If the suspicion is high, a patient will need to have another biopsy to assess for biomarkers on NGS.

Is there anything else that patients should know about NGS testing for EGFR exon 20?

The EGFR exon 20 insertion mutation is less common than the other EGFR mutations, for which targeted therapies have been FDA approved for over 15 years. Careful attention to NGS reports to determine which EGFR alteration is present has an impact on treatment decisions. Targeted therapies used to treat EGFR exon 19 and exon 21 mutations are ineffective for the EGFR exon 20 alteration.

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