Advancing Precision Medicine Through Comprehensive Genomic Profiling (CGP) - Episode 6

Types of Molecular Assays Used in Oncology

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Oncologists who manage patients with solid tumors compare and contrast current comprehensive molecular assays being used in clinical practice and discuss reimbursement criteria with payer, Eugean Jiwanmall, MPH, MBA.

Bruce Feinberg, DO: Mark [G. Kris, MD,] introduced NGS and the difference with using the NGS [next-generation sequencing] and the CGP [comprehensive genomic profiling]. Is one the test? One is the outcome of the test? I think it's worth explaining the difference. Then he mentions alumina and the analyzer and it is the company that has developed the means by which we can do the genetic profiling. How much of that then becomes a commodity and what differentiates the different companies, and even institutions, that are doing it with the same analyzer? Is it what Mark just described? It's all the research that's going into the way those results are presented. Let me have you go over the NGS, CGP, alumina, and the reporting and the differentiation?

Kenna R. Mills Shaw, PhD: The first thing that I will say is, alumina is not the only game in town. There are multiple different vendors that enable genomic profiling. There are different commercial vendors that use alumina vs Thermo Fisher Scientific vs other sequencing providers. I think ultimately it does come down to what you're covering. How much landscape you're covering in your assay? In cancer, the other big thing is whether you're doing tumor normal. If you're sequencing the tumor, do you have a germline comparison to be able to make your somatic calls which were discussed earlier, more precise? How deeply are you covering because we know cancer and tumors are heterogeneous so the more sequence you get the better, more precise your calls are. Then finally, I do actually really believe that it comes down to what we call decision support. It is that team that says, “OK we believe that your patient has a mutation in BRAF or a mutation in EGFR. What does that mutation mean biologically, clinically for that patient at that moment in time?

This information is dynamic. Not all mutations, I think Mark said that earlier, are created equally. What we know today might be new in a year and a half. We might learn something new. Making sure that that knowledge base, that information and our understanding of an individual mutation or an individual alteration is able to be referred in real time is also going to be incredibly critical for implementation of precision medicine. We did the gene study out of the AACR [American Association for Cancer Research] in their very first publication, I think had over 18,000 distinct mutations. There's no way any one clinician can possibly navigate by themselves the enormity of that task of understanding what it means for how to better treat a patient. Having those decision support resources to actually give the clinician, not just what the pathologist and the molecular laboratory provides which are those mutation calls, but that true interpretation of what it means biologically. And then most importantly tie it to what treatment is available in the clinic right now. Not theoretically. Not just level 1 indications. Not just with the NCCN [National Cancer Comprehensive Network] guideline or FDA-approved [therapies]. What might be in the pipeline in terms of the clinical trial for that given patient for that tumor type? It's that breathe and that scope that adds real opportunities I think for our patients.

Bruce Feinberg, DO: Just what a payor wants to hear Eugean. Not just what's in the NCCN guideline the world is your oyster.

Kenna R. Mills Shaw, PhD: The world.

Bruce Feinberg, DO: You have to be the bad guy. You've got to be able to say no, I know that there's a lot in there but what's the basis for that decision?

Eugean Jiwanmall, MPH, MBA: I appreciate Mark and Kenna setting me up for this. Which is good because it will drive the conversation where we need to get to where we are. As Mark has stated and Kenna has explained it as well, in simplest terms as possible that we can say, we talked about multiple categories that are established for institutions and our organizations. As if I can call differential genetics. They categorize any mutation, or probably more technically a new variation that they pick up, as lymphogenic, pathogenic, or benign. In simple terms, is it disease causing? Is it likely to cause a disease? Or is it benign and it's not going to do anything? As was stated before, not all mutations are going through that.

Then there is the unknown category. I won't call it variation of finalistic because I'll just say the unknow category. If you stick to those 4 categories that are out there: disease causing, likely disease causing, benign, or we don't know yet. From a reimbursement perspective, from an evaluation of testing perspective we run into all of those, especially when you talk about comprehensive genetic profiling.

That's what I was trying to get to earlier. You are talking about multiple markers that are at different stages of research. When it comes to basic science research and then also clinical research. Let's talk about dozens of markers. Some of them are going to have basic scientific is supported and then they need to be validated in the clinical research world. Then they are those who are a bit ahead and there's actually a period with clinical literature guidelines out there that have established these buckets I've talked about. They fall into the disease-causing scientific category or life disease causing.

Bruce Feinberg, DO: Sorry to interrupt, when you talk about disease causing that might be a very limited number. They could be done in what would be sometimes referred to as a spot test. I'm just going to look at these three things because those are the three things for which we have irrefutable evidence. As a payer, will you be judging whether that's going to be what's in pathway versus complete profiling? Which you're going to at this point is outside the path because everything else is not fitting that definitive relationship profile.

Eugean Jiwanmall, MPH, MBA: Absolutely. You've got me exactly to where I wanted to get to. From a reimbursement perspective, we cannot change how the tests are being designed. We're not at that point. We're down the line when it comes to the overall continuum of care. We are likely either at the point where we are actually ready to pay for the test or not pay for the test, or pay for it partially, or we are at the prior authorization portion of it. Somebody's calling in and checking if the organization's going to pay for it or not, still at that point. We cannot design the test as of now. Yes. In an ideal world, we would love to have only from the clinical practice perspective, routine clinical practice perspective, what you refer to rules, things that are established. The markers that are established in one way or the other. The categories that Kenna was speaking of, Mark also alluded to, either they are established to be prognostic. You know exactly what to do with them or they're going to be defined in a therapeutic manner. You have this particular marker being expressed a certain way, so you go ahead and get this drug.

Those are not the problematic things where there's actually any contention or any debate. But when we come to the comprehensive genomic profiling, we are into, a lot of times things that are still being figured out. The conundrum for payers or healthcare management is to decide between "Is it truly clinical research at this time or is it going to help split somebody in a particular clinical trial? Or is it practical, routine clinical care where you are actually going to be understanding that these results are going to impact direct patient management"?

Those are the questions that we look at when we're looking at the clinical utility of our comprehensive genomic profile. Yes, there are problems that we run into when you talk about hundreds of markers that are out there, so we have to look at it from an overall test perspective. It may turn out, and this has happened over the years— especially in the past 5 years—there are certain tests out there, which have hundreds of markers, that are part of them.. But what has happened to those tests if they do get coverage positions, positive purpose positions, is that they were able to take the overall test and showcase their actual clinical utility, or they are being used to actually influence and direct patient management. That can happen as well.

Bruce Feinberg, DO: I'm going to hold you there, because we're going to flip gears in just a minute. We're going to get into direct patient care. I want to come back to that a little bit.

Transcript edited for clarity.