Joining me today in this virtual discussion are my colleagues, Dr Joshua Bauml from the University of Pennsylvania, Dr Leora Horn from Vanderbilt University, Dr Tim Kruser from Northwestern University, and Dr Jacob Sands from Dana-Farber Cancer Institute. Today we're going to discuss a number of topics pertaining to treatment of advanced non—small cell cancer, as well as small-cell lung cancer, and discuss some of the recent data that have been emerging and how we make decisions around treatment.

Let's get started on our first topic today. One of the first things we ask when seeing a new patient with metastatic non—small cell lung cancer, is how to approach that patient in terms of our work-up and management. Josh, maybe you could start with walking us through some of that.

Joshua Bauml, MD: Thanks. When I have a patient with non-squamous disease, I do a comprehensive next generation sequencing [NGS] profile, which at our institution is a DNA-based NGS profile and an RNA-based fusion panel. And those patients also have PD-L1 [programmed death-ligand 1] testing. For patients who are biomarker negative, I go based on PD-L1 results. If they have PD-L1 greater than 50%, I tend to give them pembrolizumab monotherapy unless they present in extremis, and for patients who are PD-L1 less than 50%, I give them histology-appropriate chemoimmunotherapy, usually either carbo/pem/pembro [carboplatin/pemetrexed/pembrolizumab] or carbo/pac/pembro [carboplatin/paclitaxil/pembrolizumab].

Naiyer Rizvi, MD: Josh, you were saying that you do a DNA-based and RNA-based test for all of your newly diagnosed patients. Can you tell me a little bit more about what the RNA test is for?

Joshua Bauml, MD: Yes. The RNA test has much higher sensitivity for the detection of fusions and translocations, which can happen rather frequently in patients with non-squamous non—small cell lung cancer. So actually, if I have a patient who has had a DNA-based assay, and I suspect that there is a fusion translocation, I will sometimes repeat our RNA-based assay and have found fusions in that fashion.

Naiyer Rizvi, MD: We do something similar, but if we find a KRAS or EGFR mutation, we don't do the RNA-based assay because it's unlikely we're going to see anything more. Leora, is that similar to what you do in your group?

Leora Horn, MD, MSc: Yes. We're doing the same thing here as well.

Naiyer Rizvi, MD: OK. Jacob, any other biomarkers you feel are important up front? We've got the DNA-based test. We've got the RNA-based test. We have PD-L1 testing. Anything else that you use to inform treatment decisions?

Jacob Sands, MD: I think those are, obviously, the most important ones. And one thing I'll add to that is, even in people who have squamous cell carcinoma who are never smokers, or light with a distant history of smoking, we do test those as well. Then we had a recent publication in Lung Cancer looking at our squamous cell population and going back and looking at NGS testing from those. And interestingly, there are some where it looks like it's probably more of a metastatic skin cancer or something else like that, particularly in these non-smokers, and so just to consider that there can be other possible sources of that, particularly in that population. And we saw a UV signature on the NGS panel within that, and then looking back, they actually have a history of a squamous skin cancer that had been resected. So sometimes the picture isn't quite as clear, and it takes a little bit of digging as well. But we as well do NGS panel and a PD-L1 expression testing.

Naiyer Rizvi, MD: Do you report out TMB [tumor mutational burden], or do you use TMB?

Jacob Sands, MD: Well, it is reported out on the panel we use internally. I'll say I don't yet really see a great reason to use TMB. I don't think it's quite clear, and it's not really a tool for driving decision making at this point.

Joshua Bauml, MD: Yes. They just added TMB output to our internal panel, and we had a whole talk about when are you going to use this, we put in all this work. And I said, “I don't think I'm going to use it right now at all, unfortunately.” But I see it, and it is a thing on the page at this time.

Transcript Edited for Clarity