HRD Testing in Ovarian Cancer: Clinical Guidelines Recommendations

EP: 1.Opening Remarks from Dr. Herzog, Dr. Krivak, and Dr. Hagemann

EP: 2.Defining HRD and its Role in Ovarian Cancer

EP: 3.Other Causes of HRD: Chromosomal LOH, LST, and TAI

EP: 4.Commercially Available 
HRD Tests for Ovarian Cancer

EP: 5.Leveraging HRD Testing Results in Ovarian Cancer: Clinical Data

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EP: 6.HRD Testing in Ovarian Cancer: Clinical Guidelines Recommendations

Dr. Thomas Herzog: So I'm going to talk a little bit about HRD testing in ovarian cancer, the guideline, recommendations, and we'll get into typical workflow if there is such a thing. Hopefully, there's some consensus, but it's not even the same in our group. Depending on sort of how the patient got into the system, it can be different. So I think that we'll find some of those things will be the same. So in terms of thinking about NCCN guidelines, other organizational guidelines, and so forth, there've really been- there's a section, for example, with NCCN that looks at the pathologic principles in terms of ovarian cancer and so forth. And one of the parts of that is the tumor molecular analysis. And they really do stress the importance of looking upfront at a minimum to optimize identification of molecular alterations that can inform someone about the interventions that have demonstrated benefit in these settings. And so, just what Dr. Krivak was just talking about in terms of some of these trials that we mentioned where PARP inhibitors have really shown amazing hazard ratios. That's one of the things that I think has probably been the most transformational thing for the GYN oncology world, is to go from hazard ratios for successful studies from something that's slightly below 0.7 to 0.3 and below and now are approaching 0.2 in some of the subsets. So, pretty crazy in terms of the benefit or the magnitude of benefit that we're seeing with this. So, we brought up both upfront and in the recurrent setting. I personally believe that knowledge is power and that it gives you the best opportunity to plot that patient's journey in terms of the treatment choices you're going to make as you go through their ovarian cancer treatment landscape with them. And so, I think that having that information upfront is important. If you don't have it, and they get into your system later, getting in at recurrence is important. It's nice to know some of the other things about the tumor. We have a number of trials coming out. We've just had a trial reported at ASCO, DUO-O, looking at combinations with checkpoint inhibitors along with PARPs. And we have three other trials that'll report in the future looking at various combinations with IOs and PARP inhibitors. So, things such as PD-L1 status, tumor mutational burden, MSI status, and so forth are all, I think, important. Knowing some of these other less frequent mutations in the recurrent setting is important as well, such as NTRK fusions, BRAF. Now, folate receptor alpha is with a new approval at ASCO that- well, with an approval for accelerated approval before ASCO, and then the definitive trial report that came out of the ASCO, we'll probably see movement on that in terms of final FDA action hopefully soon. And so, this whole idea of understanding the molecular background, I think, is really important in terms of what we look at. I think one of the things that often gets lost in all this for our lower volume treaters out there who may only see one or two cases of ovarian cancer in a year or less, and then they get a case and they're like, well, what am I supposed to do? Things have changed really rapidly. Don't forget to do germline testing and make sure we know where we stand with germline testing. Not only so we have the somatic which can be an additional group up to, say, 5, 7% and some of the higher numbers that we've seen in terms of prevalence can have somatic mutations, and then you have that 15% or so that are germline for BRC1 or 2. I think what gets lost there is the fact that not only is it prognostic and then predictive of whether we can use these therapies, that opportunity to be able to do cascade testing on the family is really an opportunity to save lives. And I really want to stress that, and I don't know if Ian or Tom, you want to say anything about that, but I find people, some of the lower volume treaters get caught up in some of these other advanced tests, sort of forget some of the basics, and all our groups agree on that. So ASCO guidelines, SGO, NCCN and so forth. Any comments on that?

Dr. Ian Hagemann: Oh, yeah. No, it's lifesaving. The patient herself may be at risk for additional cancers too. So the presenting cancer-

Dr. Thomas Herzog: Absolutely.

Dr. Ian Hagemann: Could be ovarian and not breast for-

Dr. Thomas Herzog: It is a very different treatment strategy perhaps but also surveillance strategy for the patient within that patient that you find for other cancers. Correct.

Dr. Thomas Krivak: I think it's been tremendous, Tom. I completely agree. I think we do risk-reducing surgery. And when we look at the numbers, it seems like ovarian cancer fell below 20,000. It's 19,750, I think, in the most recent. So it seems like we've dropped 1,500 cases, whether that's COVID and people not going to the doctor or potentially us starting to see the effects of risk-reducing surgery and OCPs. It's tremendous.

Dr. Thomas Herzog: I agree.