EGFR Exon 20 Insertion as a Therapeutic Target in Non-small Cell Lung Cancer - Episode 3
Experts review the demographics of patients who should be tested and how to discuss EGFR Exon 20 Insertion+ NSCLC with patients.
Joel Neal, MD, PhD: We talked about testing, we talked about demographics, and that leads us to whom to test, which is anybody with non–small cell lung cancer adenocarcinoma. It sounds like, from your experience, Alex, this includes patients with or without a smoking history, which is usually what we advocate for.
Alexander I. Spira, MD, PhD, FACP: Yes, we’ve all been burned, and you’ve seen it. You’ve told people they’re unlikely, and they end up having 1 and it’s a surprise, so that’s why I hesitate to talk about who the demographics are, because then it gets into people’s heads that we shouldn’t be testing everybody. But I’ve seen it in everybody, especially light smokers or people who quit a long time ago, so it’s important to remind everybody to you test early and often, as I like to say.
Joel Neal, MD, PhD: Absolutely—don’t rest until you see a positive or the lack of all positives by the best testing you can conceive of. Backing up a little into the basic pathophysiology, what do you tell patients when they say, “What’s this EGFR mutation?” Why do we care about it? What’s it doing to cancer cells, and why is it special?
Alexander I. Spira, MD, PhD, FACP: I’ll tell you what I tell them. It’s a bit of an oversimplification, like everything else that we do, but I tell them that it’s an abnormal gene that’s expressed in the surface of the cell that essentially turns the cancer cell on. It’s a switch that should be turned off—you can turn off with some of these medicines. It’s there in normal amounts. However, when left unbridled, it causes a replication of the cancer cells, and the idea with these drugs is that they essentially just turn them off.The key is finding which drug turns which part of the molecule off, hence the need for the exon 20 drugs vs some of the other drugs that we have. I know that’s an oversimplification, but that suffices for most. How do you describe it?
Joel Neal, MD, PhD: I use the similar on-and-off analogy. I go a little further into a metaphor using a light switch and I say, “The signaling has to be on for cells to grow, divide, and not die. These switches turn on and off to make cells grow normally and go to where they should be, but this EGFR mutation makes a protein that makes the switch stuck in the on position basically.” We can use strategies; that on position makes the cells grow and makes them not die. We can use strategies to shut off the power across the board; those are the things like chemotherapy, or we can just go in there and clip the wire right below the switch. That’s what these targeted drugs do. They just fit in there, into that switch, and turn it off specifically even though it’s stuck. I don’t know if it resonates. People seem to understand, or maybe they get glazed over depending on the level.
Alexander I. Spira, MD, PhD, FACP: As soon as you tell people they have a targetable mutation and this drug specifically targets it, the rest of the conversation? They don’t care. They say, “Give me the drug.”
Joel Neal, MD, PhD: Right; “We have a pill against your cancer; great. It’s OK. Now I don’t need chemotherapy.” That’s the biggest question coming in the door, right?
Alexander I. Spira, MD, PhD, FACP: Exactly.
Joel Neal, MD, PhD: Do I have to have chemotherapy? As I say to my patients, “Nobody ever came in here asking for chemotherapy, but they figure they are probably going to get it.”
Alexander I. Spira, MD, PhD, FACP: Exactly.
Joel Neal, MD, PhD: If we don’t have something more specific for it—we covered what the role is—is there anything unique about EGFR exon 20 insertions that you know of? I don’t know that I know off the top of my head, compared to the signaling downstream as distinct from other EGFR mutations?
Alexander I. Spira, MD, PhD, FACP: I don’t think so. I don’t think there’s anything that we know yet.Everything is still a little new and novel. As we learn more about this, as we’re talking about some of the newer drugs—the duration of response and most important what the resistance mechanisms are—we learn a little more about it. But I don’t think there’s anything superunique about it.
This transcript has been edited for clarity.