Key Considerations for Detecting and Targeting BRAF Mutations - Episode 2

Molecular Testing in NSCLC


D. Ross Camidge, MD: In order to find a BRAF V600E mutation in lung cancer, you have to do some kind of molecular sequencing. I think I calculated about 5 different molecular abnormalities in lung cancer that have an FDA-approved agent, so you’re at the tipping point. Ordering single-gene tests is not viable. It’s actually cheaper to order a panel. The good news is most of the next-generation sequencing [NGS] panels are going to include BRAF V600E, and that’s where you’re going to pick it up.

The NCCN [National Comprehensive Cancer Network] says you should test everything within a broad panel. It lists all the things that have FDA-approved agents, and then it has an additional table of some of the things we’ve already talked about that are also potentially actionable, either inside a trial or by repurposing a drug already sitting in the pharmacy.

Within our own practice, we will test every advanced non—small cell lung cancer patient with a broad range. We actually do both a DNA- and an RNA-based extraction for NGS testing. We do FISH [fluorescence in situ hybridization] testing for MET because it’s really the best way of calculating amplification. We also do PD-L1 [programmed death-ligand 1] immunohistochemistry. There’s an interesting study that says that even though these agents have been licensed, if we use BRAF as an example, since 2017, in the community BRAF testing is only being ordered in about 30% of lung cancer patients. That’s a real tragedy. This is a targetable agent.

And so if you have the patient in front of you and you’re having to think, “What’s the box that I have to check,” you’re doing it wrong. What you have to do is say, “Do the lung panel,” and make sure you know that what’s in that lung panel is everything that already has an FDA approval or anything that you might want to know. If the patient was special to you and you wanted to send them for a clinical trial, you should have everything in that panel. You don’t need 1 million genes. The list of things that you can actually act on is probably less than 10. There’s a certain snob value in saying, “My panel’s got 300 genes or 400 genes.” That means nothing. Just make sure you know what’s in the panel, and ensure it’s got the right stuff.

In an ideal world, when the patient comes in, you’re sending off molecular testing. The result comes back within a reasonable time frame, and you wait for your treatment decision until you have that information in hand. Sometimes that doesn’t work. There are only certain things that are in your control. It may not work because the patient is crashing and burning in front of you, so you’re going to probably start with chemotherapy. Then that information can inform you later.

But the thing that is in your control is ensuring that the tissue that you’ve got is adequate and goes through the process as quickly and efficiently as possible. That means you have to speak to whoever is getting you the tissue, whether it’s the interventional radiologist, the pulmonologist, or the pathologist.

You all sit down in a room together. Maybe you buy them coffee, and you say, “Look, this is what I need it for.” And then suddenly, everybody is on the same team. You educate the people doing the biopsy that you want as much tissue as feasible. You educate the pathologist that you don’t want to do 15,000 immunohistochemistry tests that are fascinating to them but have no importance to the patient. There are various tricks and tweaks that you can do to maximize tissue for molecular testing. In fact, we wrote it up. It was called “Tips for Molecular Testing.”

Transcript Edited for Clarity