New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think TankIncreasing role of next-generation sequencing (NGS) in clinical practice
4:55 minutes.
TRANSCRIPTION:
DR KRIS: What this paper did is it took specimens from a group of patients that had all of our standard testing, which at the time would have been FISH testing for ALK, Sequenom for the common point mutations, a sizing assay for HER2, exon 20 insertion, the sizing assay for EGFR exon 20 insertions and looked for other abnormalities and found them. They found some that were actionable by available drugs, and they found others that would be potentially actionable through clinical trials. And I think the point of the paper is, I think, is that the more you look, the more comprehensively you look, the more you find. I don’t think that’s an indictment of the other testing. It’s just that this is a more comprehensive panel of tests. Also, when pushed, the bottom line is, you need a lot less tissue to do it, too. And it truly makes sense to do a multiplex panel. And from a cost issue and this idea that you may find something that is actionable, that you may not have thought of, this whole N of 1 movement, I don't know if we’re going to talk about that at some point today, but if you find one of these things that you didn’t expect, then you can act on it. So I was talking to David a second ago, that all of us are migrating to next-gen platforms. It’s not every case today, but it’s going to be every case shortly. And I think more and more that’s going to happen, so we’re going to have this more comprehensive information. And frankly, the challenge is going to be interpreting it. DR LOVE: So what assay was used here, and what are the available assays that are kind of available? DR KRIS: Most people use an Illumina®-based assay. They generally use the HiSeq platform. There’s a bunch of Illumina platforms out there, but most of what people call next-gen testing is done on one of those Illumina platforms. And this is a technology — David, you may know better. How many years has it been out there? What, 5 years, maybe more? And constantly being upgraded in terms of throughput and in terms of ability to deliver the results. It used to take, by the way, to do a comprehensive 300 or so gene panel it took a week to do it, to do the sequencing, and then another week to analyze it. You can now do it in a night. DR LOVE: Dave, what are the different platforms? Was this a FoundationOne® that was done? DR KRIS: This was Foundation, yes, in that paper. DR LOVE: So Dave, what are the different currently available next-gen sequencing, like FoundationOne? DR SPIGEL: Yes. So there’s several. I mean, I think Foundation Medicine’s FoundationOne is probably the one we’re all most familiar with. That’s certainly what we’ve been using a lot of. So Biotheranostics has a comprehensive panel. Clarient offers it, Caris offers it. I mean, there are a dozen vendors that offer — DR KRIS: Quest. DR SPIGEL: Yes. I think the real discriminator is going to be what does comprehensive mean? Is that a 35-gene panel or a 300-gene panel? And for me, it’s been, how good is the reporting, how fast the turnaround time and how often do I get back a report saying “quantity not sufficient for analysis”? Those, to me, are the things that make a test useful. DR LOVE: And is this, for example, or is the American College of Pathology or ASCO trying to look at the various assays and put them in context in terms of quality? I mean, we went through stuff like this with breast cancer and HER2. DR SPIGEL: So, in short, I’m not aware of any of that happening. Certainly, our payers probably will determine who survives kind of this arms race and who’s left standing. But no, I’m not aware of any quality comparison efforts. DR KRIS: There have been some. There’s a paper that again, using the Foundation panel, where they took, actually, Sloan Kettering specimens that were analyzed by our standard methods. And when you used the same DNA specimen in a Sequenom versus a next-gen, there was virtually 100% concordance. DR LOVE: So there’s not much of a quality control issue in terms of actually doing it? DR KRIS: For point mutations, probably not. It gets more difficult for complex rearrangements. And how these panels are created changes the comprehensiveness of the data that comes out. And it gets more subtle with the rearrangements. But for point mutations, it’s dead on. |