Case 2: Testing for EGFR in Lung Adenocarcinoma

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD:The world has gotten complex in lung cancer, and it does take an incredible amount of communication and coordination to execute the plan in the right way, especially with next-generation sequencing, PD-L1 [programmed death-ligand 1] testing, and how we divide and conquer as well as how we prioritize the information we receive back. Isabel, you know this is a patient who has PD-L1 testing done that comes back, as Sam says, within 24 to 48 hours. That’s your first test that you get back. If your patients are anything like mine, they’re knocking down the door for KEYTRUDA [pembrolizumab]. They see the ad on television, and this is what they want. But this is a patient who has never smoked and who has a high chance of harboring anEGFRmutation. How do you manage that, and do you wait for theEGFRtest to come back before making decisions? How do you manage a patient like this?

Isabel Preeshagul, DO, MBS:I think you raise an excellent point, Ben, and I echo what everyone else has mentioned so eloquently aboutEGFRtesting. I think in a patient who has never smoked, if you have a PD-L1 of 50% or greater, it’s very easy to get trigger happy and to want to offer them single-agent pembrolizumab up front. However, I think you have to take a step back and think, “This patient has never smoked. The likelihood of them having anEGFRmutation orALKorROS1is possible.”

Maybe you want to take a step back and think, “Why don’t we wait?” Is there a way we expedite this testing? This might be a point where I would reach out to the pathologist, and I would say, “This is my patient. She’s a never smoker. She’s symptomatic from her disease. What’s the turnaround time for getting theEGFRresults back?” I would have a discussion with my patient about that and encourage her to wait for theEGFRtesting if she’s relatively asymptomatic.

Benjamin P. Levy, MD:Yeah. We’ll go through why in a second, and we’ll present some data on how lousy a drug immunotherapy is forEGFR-mutant lung cancer. It’s quite incredible. Before we do that, we’ve had a lot of data recently on liquid biopsies. Are you using liquid biopsies a lot in your practice for genomic interrogation of these patients, or are you still relying mostly on tissue?

Isabel Preeshagul, DO, MBS:I think it’s very institution driven. But if I’m seeing a patient as a consult who is very symptomatic from their disease and is a never smoker, that might be someone who I might offer liquid biopsy on to expedite the testing to determineEGFR.

Benjamin P. Levy, MD:Yeah. We’ve got data now just published 2 weeks ago suggesting that every patient with an advanced non—small cell lung cancer should have tissue testing but—no offense, Sam—should also get a liquid biopsy to expedite the genomic interrogation, and the data suggest that maybe doing them in parallel will expedite the result. Have you had a lot of questions from medical oncologists about liquid biopsies?

Samuel Caughron, MD:Liquid biopsies are hugely challenging, right. What do we do with them? Where do they fit in the cancer-treatment spectrum for diagnostic work-up? I have got a lot of questions. Interestingly on the back end in the lab, it’s the same process whether it’s the tissue or the liquid biopsy. I think it’s just operational. We have really streamlined our operations by reflexively testing virtually every patient, so we don’t see a lot of liquid biopsy used because we get those results back on the chart. Now the question becomes, do we get additional information with the liquid biopsy? Let’s set aside the timeline question. Do we get additional information that is challenging? What we do know is, if you get a negative result, you can’t trust it.

Benjamin P. Levy, MD:That’s right.

Samuel Caughron, MD:We’re looking for circulating cell-free DNA. Not all tumors are shedding. If you get a negative result, you can’t trust it. One of the things I caution, generally with molecular testing, is a positive result. We’ve not had to worry about false positives. With some of these tests, we’re pushing the sensitivities of the detections to the point where we’ll pick up a mutation in the peripheral blood. Is that a false positive, or is it tumor heterogeneities when you compare it with the primary tumor? Or do we have tumor heterogeneity, and we’re just seeing them more advanced where you’ve got now driver mutation?

I don’t think that question is fully answered yet. The role of liquid biopsies is still to be determined. They’re certainly gaining in popularity. I urge caution, and I encourage optimizing your up-front tissue for specimen processing to get those results as soon as possible because that’s still the gold standard.

Benjamin P. Levy, MD:You’re well versed in the liquid biopsy lingo. I think this is an ongoing discussion. I agree with you. The sensitivities are getting so low with liquid biopsies that you’re able to pick up on subclonal mutations, or what I call schmutz. Whether it’s real or not, I think that we are going to see an increasing ever-present role for liquid biopsies in advanced-stage disease. It may be able to add additional information that was missed in tissue because of tissue heterogeneity, or QNS [quantity not sufficient]. I think we’re just beginning to scratch the surface here.

Transcript edited for clarity.