NSCLC Targeted Therapy: EGFR Exon 20 Mutation - Episode 1

Overview of EGFR Exon 20 and Molecular Testing in NSCLC

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Experts explain the presence and role of EGFR exon 20 insertion mutations in non–small cell lung cancer and highlight the role of molecular profiling.

Transcript:

Estelamari Rodriguez, M.D., MPH: Hello, and welcome to Cure Expert Connections® on exon 20 [EGFR mutations] in non-small cell lung cancer. I’m Estelamari Rodriguez, M.D., MPH, and I’m associate director of community outreach and co-lead of the Thoracic Disease Group of the University of Miami Sylvester Comprehensive Cancer Center. I’d like to welcome Katina Bland. Please introduce yourself, Katina.

Katina Bland: Absolutely. Thank you for having me, Dr. Rodriguez. My name is Katina Bland, and I am pleased to be here today with you. I am a member of the Exon 20 Group’s advisory council, and I also am the chair of the Speakers’ Bureau. I have the privilege of also being the care partner for my beloved husband, Martell Bland, who also was an exon 20 patient with ICAN [International Cancer Advocacy Network]. My husband and I established the educational program called the Martell and Katina Bland Patient Education Program.

Estelamari Rodriguez, M.D., MPH: Thank you for all you’ve done. I really believe that, we have known about EGFR mutations for a long time, but we are finding that there are subgroups of patients with EGFR mutations that we didn’t know how to treat because we didn’t understand that all these receptors, all these mutations, can respond differently to treatment. I just wanted to cover a little about the significance of EGFR mutations. EGFR has been well established as a very common driver mutation for non-small cell lung cancer. It accounts for about 20% to 25% of mutations in non-small cell lung cancer. The EGFR [exon] 20 insertion mutation, which we previously had lumped together with all the EGFRs, we have known that patients who have this exon 20 insertion mutation either get missed in the process of diagnosis or they get treated with the existing EGFR targets that were previously used for the common mutations, and they were not responding as well.

There has been a lot of research in exon 20 insertion mutations to understand what would be the best target for these patients. These are seen in 4% to 12% of EGFR-mutated cases. We know that the more common [mutations] that have been tested in the larger trials with the older generation drugs are deletion 19, and L858R on exon 21, but this particular exon 20 insertion is important to recognize because now we have treatment options. Katina, I wanted to ask you a bit about when your husband was diagnosed. How was that discussion of understanding his mutation, and at what point had they figured that out for him?

Katina Bland: Well, we figured that out relatively soon because our oncologist ordered NGS testing for him and that was critical. NGS stands for next-generation sequencing testing. It is absolutely critical that we use that form of testing because that is more accurate than any other form of testing you may have heard of, including something that’s known now as PCR [polymerase chain reaction] testing. Most people have heard of that as it relates to the COVID-19 era now. PCR testing leaves quite a bit undiagnosed, maybe 50% of EGFR exon 20 insertion mutations are not caught with PCR testing. It is critical that the platform for testing and the standard needs to be the NGS testing because biomarker testing is the way to go, to have your tissue and your liquid biopsies tested in that method.

Estelamari Rodriguez, M.D., MPH: I’m glad to hear that you and your husband had that information at the beginning of the treatment because, unfortunately, many patients either don’t get the right test up front or it gets missed because there’s an urgency to treat, and patients have been started on chemo [chemotherapy] and immunotherapy, where we know that patients who have driver mutations will be better with targeted therapy. It is very critical to have this at the time of diagnosis. Just to summarize what you said, the NCCN [National Comprehensive Cancer Network], which sets the standards for cancer care in the United States and internationally, has outlined comprehensive molecular testing, molecular profiling of the tumor, as standard. We have about nine targets that today are considered druggable, for which we have a drug, and we have many that are in development. Having as much information as possible about the tumor genetics and the molecular drivers will open doors for treatments that are available today.

Some of the treatments we will discuss today are very recent. If you don’t do this test, when the drug gets approved, you will have missed the opportunity. You mentioned something really important; I think it’s very hard for patients. You get these reports that, even for physicians, are very hard to comprehend. Sometimes they have a summary slide, and you don’t know what type of test was done. Was it an immunohistochemistry, which is a very simple expression of a protein? Or was it a PCR, which you mention can be just a single gene evaluation? Or was it an in-depth next-generation sequencing, which is more comprehensive and looks at the whole genome of that tumor? Those are the ones that would allow us to pick specific findings like the EGFR 20 insertion.

Transcript edited for clarity.