Advanced Lung Cancer: A Year in Review - Episode 9

Lung Cancer Molecular Testing Protocol


Naiyer Rizvi, MD: We talked a little bit about upfront treatment for lung cancer, particularly adeno [adenocarcinoma] or nonsmokers. We explained that we would do molecular testing, consisting of DNA- and RNA-based testing. We're going to talk next about targeted therapies.

Jacob, how hard do you look for the rarer mutations, fusions, and what's your approach at your center?

Jacob Sands, MD: Well, we do an NGS [next-generation sequencing] panel. We don't tend to do as much of the RNA-based testing as Josh initially outlined unless there's somebody where we're really highly suspicious, someone who really is a classic population. But I tend to use targeted therapy initially. That includes even BRAF V600E, which I know there are some differences in practice, but EGFR/ALK, ROS1, MET amplification, MET exon 14 mutation. We have the RET fusion trial. As far as looking for some of these other ones, I think in the lung cancer world, we really benefit from the fact that NGS is really standard of care practice. Some of these other rarer mutations we are going to capture, versus in some of the other cancer types where NGS platforms are not really the standard practice. We use a broad NGS panel, and I tend to use targeted therapy up front in general.

Naiyer Rizvi, MD: I think everyone would agree that we do want to have the molecular results before we start therapies, particularly for adenocarcinoma. I don't think we can rely on smoking history. So in general, everyone should have the more common mutations and fusions before starting therapies. But material can be an issue.

Josh, you can talk about tumor versus plasma. When do you send plasma? Do you do it in parallel? I know you guys published something around the Guardant360 assay. What's your approach?

Joshua Bauml, MD: Yes. My colleague, Charu Aggarwal, MD, MPH, just published a really good paper working with Erica Carpenter, MBA, PhD, who heads our circulating tumor materials lab at the University of Pennsylvania looking at the concordance between the Guardant360 plasma assay as well as tissue testing in patients with non—small cell lung cancer, going beyond EGFR and showing that there's a high concordance, that this can highly predict responses, and that we can identify alterations that would be missed on tissue.

I have a very low threshold to send a plasma assay when I see a patient for a new diagnosis. If I get a second opinion, the tissue is somewhere at another institution, I don't know when it's coming here. I don't know what it looks like. I don't know how big the block is. I will send a plasma. If I have a patient where they've done a biopsy and I don't know, there's something on the pathology report that makes me a little nervous, I will send a plasma. The other advantage of sending a plasma is it comes back in a week generally, whereas our tissue-based assay takes 2 to 3 weeks, sometimes longer, if things are rough. Getting that result quickly can make a big difference to the patient. What you were saying before, Naiyer, about waiting for the results, I really want to echo and emphasize. I think it's so important, particularly with immunotherapy, because if we start immunotherapy in a patient who is going to need targeted therapy, we may be burning a bridge for their future therapy. I think it's absolutely essential we get that data. It's important to remember that plasma is not 100% sensitive, so a negative plasma result is not terribly illuminating, but if you have a positive result you can act on it, and that’s very helpful for patients.

Jacob Sands, MD: Or if you look at the KRAS mutation, for example, then they're not really going to have a targeted option it seems. It's so important, and to add to that if I can, I've seen someone from the community who had long-term control on their prior lines of therapy. At their initial diagnosis, they had just a focused panel sent, and BRAF V600E was not part of that. So also looking back and recognizing what was particularly tested on that initial one and make sure you are capturing everything now. This patient did end up having BRAF V600E and has done well on targeted therapy at this point. So looking back at that.

Transcript Edited for Clarity