Commercially Available 
HRD Tests for Ovarian Cancer

Dr. Ian Hagemann: There's a number of tests available. I was mentioning just a moment ago, there is not very good standardization. And so we have to be careful when we're reading the results of trials that have been done with HRD as a covariant because you got to understand how that trial was characterizing the tumors for HRD. There are two tests that have an FDA label currently. The FoundationOne assay and Myriad myChoice CDx are both FDA approved in a specific context, and they all take a little bit different approach. I won't necessarily go through the whole detail, but all four of the tests that are listed here. So, there's also Caris Molecular Intelligence reports out HRD and Tempus also does. These are all feasible on formal and fixed paraffin-embedded tissue, so your routine clinical tissue. They have a little bit different approach to measuring HRD. They all look for BRCA mutation, but then the myChoice assay looks at LOH, TAI, and Large State Transitions. The others that are listed here look primarily for loss of heterozygosity as a form of genomic scarring. And there are also a number of what I would call take-home kits. So there's a TruSight sequencing platform or sequencing assay that can be done on the Illumina platform that can be used to report out a genomic instability score. And so some labs will run this in their own institution. There's an Oncomine assay from Thermo Fisher, which is Ion Torrent platform. And then SOPHiA Genomics is also offering a kit that's able to detect mutations in 28 homologous recombination genes and also report out a genomic integrity index. So, I'm not here to say that any of these are good or bad. The commercially available assays are certainly easier to obtain, and they all come with their caveats.

Dr. Thomas Herzog: Ian as a pathologist, at WashU, do you have - do you do a lot of this in-house now, or do you cooperate with the commercial labs, or is it a hybrid, or something different, or do you use mostly commercial for determining HRD, for example?

Dr. Ian Hagemann: Yeah, to be candid, we do not have an in-house HRD assay at this time. So, these are sent out to the clinician's choice, and one of the assays that's mentioned here is used preferentially by our gynecologic oncologist. I think that's sort of a matter of preference. But, yeah, it's not an assay that we run in-house. We do have sequencing platforms and probably could bring it up, but that's been a matter of crosstalk between the clinicians and the path lab.

Dr. Thomas Herzog: Yeah, I think it's always challenging because you need such economies of scale to be able to do this where you're not losing money, because these efforts all take a lot of capital, both number of employees and so forth and maintenance.

Dr. Ian Hagemann: Absolutely.

Dr. Thomas Herzog: Dr. Krivak, what do you do in terms of do you do it centrally in-house or do you send it out commercially or how does that work?

Dr. Thomas Krivak: So we send it out. I completely agree with you. I think it's economy of scale, and we want to make sure that we do it well. I do think that how I use HRD and a lot of folks at our institution it's a critical time point for upfront, how we're going to do maintenance therapy. And so, my preference is again, I'm not here to say this is better than this. I've just been very comfortable with the Myriad test and up front we'll recommend the Myriad test up front. Some of my partners will use Foundation, and again, a lot of people will like Caris and Tempus. I do think the Illumina is a very interesting thing to do in-house. And we've started with our molecular path about talking about doing that test. It has a quick turnaround, but I think the first time that we do the Illumina test, we're probably going to send it out to Myriad or to Foundation to make sure we have some agreement. But I completely agree. I think turnaround time, I like the Myriad test because it gives us a BRCA mutation. And if we have a germline-negative patient and we have a somatic mutation, I generally always go back and make sure that that mutation was looked at in the germline to make sure that we're not getting fooled with respect to that. So, we send out and, again, I think all these tests are good, but to me, my bias has been Myriad.

Dr. Ian Hagemann: You're making me think of something, Tom, there's no gold standard in this space. The gold standard is probably a patient-related endpoint. So, until we have a gold standard, it's going to be hard to define a best test.

Dr. Thomas Herzog: Yeah. No, I understand and-

Dr. Ian Hagemann: They're going to reach the-

Dr. Thomas Herzog: Different capabilities in terms of how many SNPs they have across the genome and so forth. We use a lot care at our institution because we're a center of excellence that allows us. I know you are, I think, too in WashU for the POA. You're able to do some of that, but all these things are you weak side things rather than the central quality of the test itself, we think, but we'll hopefully get more information on that with patient-driven outcomes. Great.

Dr. Thomas Krivak: I think clinically it's important to define it. And what I mean by that is patient 65 years young, stage three C, high-grade serious cancer, BRCA germline negative, HRD test negative by what test? And just so when you're looking at this and you're looking at strategies to make sure that everything is lining up. And, again, I think when you do that, you make sure that you've done your germline testing, and if you believed in HRD testing, that you're at least making sure that you check that box, whether it's Foundation, Caris, Tempus, Myriad or whatever.