Alicia Morgans:  Hi, my name is Alicia Morgans and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University in Chicago. I'm so excited to have here with me today, Dr. Oliver Sartor, who is a Professor of Medicine AND GU medical oncologist at Tulane, as well as being the medical director of the Tulane Cancer Center, all in Louisiana. Thank you so much for being here with us today, Dr. Sartor.

Oliver Sartor:  Pleasure to be here.

Alicia Morgans:  Wonderful. So I wanted to talk with you a little bit about the Foundation CDx liquid biopsy that is newly out and available for use as a way for us to identify patients to treat with rucaparib. And I was just wondering, can you tell us a little bit about this assay and how it can be helpful?

Oliver Sartor:  Well, first of all, this is brand new, Alicia, it just came out on August 25th approved by the FDA. And I think it's a really important assay because it's a liquid biopsy, it's a circulating tumor DNA, that serves as a predictive biomarker, and in prostate cancer, it's really the first one. And it turns out that it's matched in with rucaparib, which is the PARP inhibitor. That was FDA-approved back in May of 2020, so just a bit earlier this year.

But I think all of us know that, during the COVID era, in particular, there's difficulty in getting tissue from patients, and difficulty in getting biopsy from patients. This is just a blood draw, and that really is a differentiator. So you can draw the blood, send it off to Foundation Medicine, you have to do this companion diagnostic, the so-called CDx. And if you have a BRCA [inaudible] and it's only BRCA1 or BRCA2, it's none of the other DNA repair genes. If you've got an altered DNA within the BRCA1 or BRCA2 genes, this assay will serve as a predictive biomarker and you can prescribe a PARP inhibitor. I think it's a big deal.

Alicia Morgans:  I think that's great because one of the things that are so important about these PARP inhibitors is that we actually do need to do some testing to identify which patients are going to benefit most. And I think we've talked about it before and probably everyone who's listening knows, that we have to look both at germline mutations, but we also have to look at somatic mutations. So this [inaudible] that we're not going to find in a germline test if we're just doing a blood draw or any one of those on our patients and this can actually double the number of our patients for many of our [inaudible], who are going to be eligible for PARP inhibitors.

Oliver Sartor:  Absolutely, Alicia, and that's a great point. The germline testing is pretty cheap and easy, and there are a lot of ways that you can get the germline. I'm not going to endorse any particular assay, but it turns out that the somatic, it will double your overall BRCA numbers. So in some of the initial studies, they would find about 18 of the BRCA somatic and that about half of those will be germline and have a somatic innervation. So whatever you find in the germline, this will probably double your numbers overall. So it'd take you from 9 to 18, for instance. So it identifies a lot of patients who wouldn't otherwise identify. And somatic testing is essential to find these patients that could benefit.

Alicia Morgans:  Absolutely. And so we really should emphasize that this is going to identify patients with mutations in BRCA1 and BRCA2. So these patients could be then treated with rucaparib, but also would be eligible for treatment with olaparib. But for rucaparib specifically, that's really approved for patients with a BRCA1 or a BRCA2 mutation. The other mutations don't necessarily apply, at least by the FDA label. So when you're thinking about this particular test, how would you work this into your workflow as you're trying to help identify new treatments for your patients?

Oliver Sartor:  I try to get a circulating tumor DNA at the time of progression. If somebody is responding to an agent, then I don't really need to go out and seek other possibilities. But, within the context of patients who are progressing, then this does open up the universe of other possibilities for that patient. And we could have a little debate over exactly how many patients will end up having a BRCA1 or BRCA2, but I think almost everybody will say at least 10%. and that's a very important 10% because we do have a drug that is FDA approved that can target that. So as we move forward, I think that this is an addition to our armamentarium. Yes, the drug is important, but in this case, without the companion diagnostic, you really can't use the drug. So the companion diagnostic is just as important as the drug itself.

Alicia Morgans:  Absolutely, because we know that these PARP inhibitors are not going to be effective except in that population that does have these alterations. Although of course, there's interest in combining PARP inhibitors with other agents that may increase the ability to treat other patients as well, but for now, that's where the indication,

Oliver Sartor:  Right. There are a lot of trials with PARP inhibitors in combination and there's even a randomized phase 2 that looks kind of interesting in combination with abiraterone. But I don't think we can, at this point, recommend a combination with PARPs, because we just don't have the data from phase 3 yet.

Alicia Morgans:  Absolutely. And so the other point that we should make is that, when we're talking about patients, and you mentioned progressing patients, which I completely agree with, we should just make sure to emphasize that this is really going to identify treatment options at this point, for patients with metastatic CRPC prostate cancer. We don't really have an indication in the metastatic hormone-sensitive setting for a PARP inhibitor. And so maybe as patients are progressing from metastatic hormone-sensitive disease with their combination therapy, that would be a great time to integrate a liquid assay, like Sr. Sartor said, really just a blood draw, or at any point in the timeline after that, if you have not yet done that testing. But this is now, testing for these mutations, both somatic and germline, is really standard of care at this point and needs to be worked into our algorithm.

Oliver Sartor:  Absolutely, I agree. Yeah, one thing about the rucaparib. It is FDA-approved after one of the novel hormones, such as olaparib [inaudible] enzalutamide and a taxane. The olaparib could be after a novel hormone without a taxane. My understanding is that this companion diagnostic is specific for rucaparib because that's where the work was done. And so, although it may be tempting to extrapolate to olaparib, I don't think that those studies have formally been done yet.

Alicia Morgans:  That's a great point. Thank you for really clarifying that. Dr. Sartor. And so, as we move forward, this assay can be used to identify patients who have a BRCA1 or BRCA2 mutation. It does seem to identify those patients who are going to, hopefully, respond to rucaparib, and find a way for these patients to have an effective therapy as they move forward with their metastatic CRPC treatment.

Oliver Sartor:  I just want to mention one more thing. They actually, within the release, sort of stated what the response rate was. So the objective response rate for those with tissue testing was 44%. The objective response rate for those with circulating tumor DNA testing was 46%. So it is just as good.

Alicia Morgans:  And as you mentioned before, so so critically important in this era, where doing extra biopsies can be challenging for many reasons, including patients having more engagements with the healthcare system, but also lack of availability, sometimes, of elective biopsies. When staffs are short when we can't have patients, as many as we used to, going through each treatment or biopsy room because we really are trying to limit exposure to our patients and distance, even in our clinical spaces. So thank you, and what final thoughts would you give to listeners who are trying to learn about and integrate this into their practice?

Oliver Sartor:  Well, I think it's a lot easier to do a blood draw than go hunt down the tissue.

Alicia Morgans:  Well, that is a great final thought and we will keep up this conversation, Dr. Sartor because I think that there's so much we need to learn and explore in the somatic and germline genetic testing that we need to do for our patients with prostate cancer. I really look forward to talking again.

Oliver Sartor:  Good. Thanks, Alicia.

Alicia Morgans:  Thank you.