NeoGenomics, Inc. (NEO) Earnings Call Transcript & Summary

Good morning, and thank you for joining us for today's Molecular Breast Cancer Tumor Board, the first of 2023. We are very excited to have you with us today. I want to share a few reminders before we get started. [Operator Instructions] As always, share cases on what makes this program successful and we encourage submission. Did you have a case you would like to present at one of our tumor boards, please send an e-mail to medical affairs at neogenomics.com. The programming today is brought to you by the Medical Affairs Department and NeoGenomics, whose aim is to foster education and promote the understanding of cancer within the global scientist community at large through programs that enrich medical and scientific knowledge of cancer diagnostics that point the way towards advancing cancer patient care. In addition to our breast cancer tumor board, we will offer a variety of educational programs throughout the year. Please stay tuned for announcements coming soon on our upcoming programs. Our host today is Dr. Fernando López-Díaz, Director of Clinical Science and NeoGenomics. Our moderator today is Dr. Jayanthi Srinivasiah, Dr. Jay as she is affectionately called by her patients. Dr. Jay is a medical oncologist with 3 decades of experience. She is actively involved in the field of research, hereditary cancers and genetics as well as breast cancer. She has been honored numerous times as a top doctor in Atlanta Magazine, Atlanta Woman, M.D. News, World Health Report and Hospital News among other publications. Dr. Jay participates in multiple hospital leadership committees, national and international tumor boards and serves as a principal investigator for clinical trial. Dr. Jay's special interest include care of breast cancer patients, including genetics, genomics, new drugs and clinical trials. We've got 3 great cases to discuss. So I'm going to turn it over to Dr. Jay to get it started. Dr. Jay, welcome. We are so glad to have you with us today.

Thank you. Thank you, Julie. I am so glad to be here. But before we begin, Susan Quarles has been our coordinator for the last few tumor boards that I've done, and I thank her for everything, and we're going to miss her. But Julie is equally excited, and I'm so glad she's here as well, and I worked with her too, and thank you for the introduction. So we're -- whenever we choose cases for breast tumor board, this is -- since this is more a genomics type tumor board, we have always thought about doing cases that have genomic data. But in breast cancer, when do we do genomics, how often do we do genomic testing or molecular testing is still in the process of evolution. And actually, I've picked a couple of cases that I have still not done the genomic testing on, and I would, of course, welcome questions from the participants and also to see when they would do genomic testing in these 2 patients. And of course, look at the other biomarkers and kind of plan treatment for these 2 patients. And then we have another third case, which Dr. López-Díaz will present. And that does have some genomic data and we'll discuss that as well. So if we can advance the slides from me. Okay. So in this case, AB is a 74-year-old woman though clinically, she has a performance status of 0 to 1. She was diagnosed with breast cancer almost 3, 4 years ago, had -- or a little bit more, had Stage 2A breast cancer, was ER/PR positive and HER2 2+ at that time. We did FISH testing for the HER2 receptor, which was negative. And she did receive adjuvant chemotherapy because of her node positivity with AC followed by Taxol and received hormonal therapy and she was on hormonal therapy when she came to me with pain and discomfort in her right breast and right neck about a year ago. Next slide. Do we have the next slide? Yes. So then when -- these are some of the treatments that she has had, and I just want you to look at when she was diagnosed with the recurrence in her -- of her cancer, this was March of '22. She had presented with the right breast, which was the previous cancer post lumpectomy and radiation, had swelling in the breast, thickening and nodularity pretty much towards the breast and right neck adenopathy. And she had missed her appointments ever since, I would say, 2 or 3 years. So she was originally diagnosed in 2012, received adjuvant hormonal therapy. And I don't know if she continued beyond 2016, she said she was still taking it when she presented in 2022. I usually treat for 10 years based on the risk categorization, but she had missed her appointments and then she presented in March of 2022. So we did a biopsy of these breast thickened areas, and we have a pathology to look at. Next slide. Can you go to the next slide, Julie or Susan?

This is the last slide we have on...

Is that all you have?

Yes, one second. Let me check.

No, there should be more -- they were of the pathology slides. So I'm going to go ahead and tell you what we found so we can do the discussion. So basically, she had an ER/PR positive tumor, just like she originally had, and then the HER2 receptor was again equivocal. So we sent off the FISH testing, and it was negative again. So very similar histology. But this time around, she had extensive right supraclavicular nodes, there was axillary nodes and tiny lung nodules that had developed from the previous time. So this was metastatic breast cancer. And usually, after this many years of chemotherapy and because she grew on the heels of hormonal therapy, I decided to go with the Abraxane as my first line of treatment. She received Abraxane for 4 months with excellent response. And then I decided to go with maintenance hormonal therapy and since she had been on exemestane, she was given fulvestrant with Ibrance as the maintenance regimen as she was ER positive and metastatic. So at this point, the main topic of discussion that I wanted to bring up with her was that she was HER2 2+ and FISH was negative. So I'm now deciding in this last few weeks when she presented to me, she has been on fulvestrant and Ibrance, but she started feeling more pain and discomfort in the right breast, the right neck adenopathy seems to be growing a little clinically. I have scheduled her for a CT and bone scan to document progression but I'm not -- to document progression. So if she truly shows progression in this next scans, what would I do as my next line of treatment. So this would be failing exemestane, maybe failing Faslodex and Ibrance. So -- because she was HER2 2+ I feel that we could consider Enhertu, which was looked at in the Destiny 4 trial, where we randomized patients to the best treatment that the physician picked to Enhertu. And I'm leaning towards that, and I thought we would discuss this case, but I will have Dr. Lopez-Diaz make any comments on the pathology. I'm not sure why we are not able to pull up the pathology on this patient.

Yes, I was trying to find out. Thank you, and good morning, everybody, and thank you, Dr. Jay, for bringing up this case discussion. I think that as you mentioned at the beginning, the first thing that we -- I would be definitely surprised by the patient showing a change on the HER2 status and basically the amplification, the FISH amplification results changing in this way. That would be one thing. The other thing that you were mentioning and you did that at the beginning, the patient is up for Ibrance. And we'll have in the second case an extensive discussion around the topic. But you mentioned that, well, you don't have yet genomic testing for this patient, and you're trying to decide what to do with patient and if a patient is going to Ibrance and basically fails therapy and you are thinking whether you want to put the patient into a different CDK4 inhibitor, Ibrance is palbociclib, a CDK4 inhibitor. There is a number of publications and presentations at AACR and ASCO as well for different CDK4 inhibitors whose response is dampened in the presence of disruption of the E2F/CDK4/RB pathway. And in this regard, that makes a precautionary call for the genomic testing not being done yet. And basically, if you're going to decide into a targeted therapy, you might have a good view of what are the odds for those therapies against other therapies, as you mentioned, estrogen-related therapies or so on. At the same time, there are other alterations, like alterations in the estrogen receptor gene itself, which can be predictors of a good response. So all this information now in the era of genomics as we live in right now that is accessible at our -- at the physician's fingertip is really much -- I don't want to say easier, but it really has much more information to ponder on those decisions, having those genomic testing, even at these stages where you do have a clear indication for -- well, the patient is HER2 -- let me -- I don't want to represent wrong. I want to say...

Correct. Yes, I agree with you. I think at this point, we definitely -- I just sent it off now that we were going to present this case. But because she looks like she's progressing with the C4/6 inhibitor and fulvestrant. That's about the right time, I would think genomic testing would be worthwhile mainly looking at several things. One, the PIK3CA mutation to look at Piqray plus continuing fulvestrant or other hormonal AI in addition to the fulvestrant if she's PIK3CA positive. The second is to look at ESR1 mutations, maybe that will tell us responses to [ elicit trend ] which will be hopefully available soon, which is the first oral SERD that will be available. So that is another option. The third is to look at HRD assays to look at maybe genetic treatment with the PARP inhibition. So that would be helpful. Then, of course, looking at other targets as well that are unusual like AKT and consideration of clinical trials for the future. So my plan is to proceed with the genomic testing. And as you mentioned, the RB gene would tell us well if they were positive for a mutation should we avoid a next line of C4/6 inhibitors. The data is still not out for a second repetition of a C4/6 inhibitor with another hormonal therapy after failing palbociclib. But of course, now we're doing ribociclib as our first line. This was started to do that as our first line in which case we could maybe look at abemaciclib along with other drugs -- other hormonal therapies for the second line. And there are some small studies, but we're still waiting for more data to mature about a second line C4/6 inhibition, which, again, this genomic profiling may help us decide if that is worthwhile or not. So lots of different questions can be answered with genomic testing at this point. And we will represent this case when we get the results back. But I just wanted to kind of present this and have this discussion, and I'm open to any questions from our participants because this is the dilemma that we face in real clinical medicine as to whether -- when and how we do genomic testing for ER-positive breast cancer. Now -- so for this lady, I feel like I have kind of narrowed it down that I will look at Enhertu as my next line of treatment if she is progressing. And then I will wait for the genomic testing and then decide on the next line of therapy based on that was my thinking. Any other comments, Dr. Lopez-Diaz?

Yes. Well, there was one particularity about this patient that this patient has about 10 years of history of cancer. And the first presentation was a ductal carcinoma in situ with metastatic disease -- regional metastatic disease to the breast, which is ductal carcinoma in situ, it is a disease that when sentinel node is negative, the risk of progression and relapse is low, and the patient was deemed a low recurrent prognostic by certain tests provided by a laboratory back in -- at this time. And it is among these 10% of patients with ductal carcinoma in situ that would actually progress into a metastatic disease eventually...

Well, this lady did have invasive breast cancer. It wasn't just ductal carcinoma.

Yes. It is -- no, it was invasive, but it had the ductal.

Oh! Okay, component, yes -- component of ductal Okay, I got it.

It has a component of ductal carcinoma in situ, which had been at the time of the diagnosis, which was invasive. It had the ductal carcinoma in situ with the invasive lesions. So it was already these -- among these 10% of patients that with ductal carcinoma in situ get an invasive disease, so that's the peculiarity of the case.

Yes. I thought it was a fascinating story that she recurred quite -- several years later. My thinking is maybe she stopped her hormonal therapy somewhere in between though the history was very patchy because she kind of didn't show up for a while in between. So very interesting case, and I'm glad that we have so many options of therapy at this point. I'm hoping for any questions from the audience. Are there any questions, Julie or Susan?

We're not seeing questions. I am not. Maybe, Julie, are you seeing questions from the audience.

No questions at this time, we could probably proceed to the next case.

Okay, so we will answer any questions later on, we can go to case #2, and then we'll -- and after 3, we can have that discussion.

Okay. I think next slide, yes. So this is a case indeed that we brought it in -- just to bring the topic of -- in the case of HER2-low patients, there are viable new therapies for them. Some of them involve actually the use of CDK4 inhibitors, not palbociclib but abemaciclib and another therapies. And we brought in this patient because this is a typical example where the genomic testing can provide an additional landscape information of what is the context for these patients and those therapies and also because it shows how mutationally speaking or genomically speaking, it can be -- there is a variety of options for patients and how I hate to use that word, but how we genomically speaking, this tumor is. As you can see, these patients which I have -- do we have here -- the patient's age wasn't here.

It's 88, right there.

I'm sorry. It's a female, 88 years old patient. And the patient when it was tested in the laboratory, and patient has an invasive carcinoma. And when it was tested in the laboratory, I'll mention the 4 genes that they were found to have pathogenic mutations, KMT2C which is actually an epigenetic-related gene; PTEN which is a [ cell growth ] and deletion gene related to [ ribosomal interface ] and progression; RB1, which we're mentioning is the gene that is regulated by the CDK4 genes and it drives cell proliferation and TP53 as we know is the guardian of genomic stability in the cell. So 4 genes that were found with mutations. I'll tell you also some of the data that we have for the patient in terms of FISH. There was found also, not just the PTEN mutation, which is an inactivating mutation, but also a PTEN deletion by FISH. So there is a double hit on that specific gene. There was MYC amplification and the FISH for HER2 became indeterminate. So one thing related to the FISH first is that MYC amplification has been found in most basal-like carcinomas in that molecular subtype typically triple-negative breast cancers would come with MYC amplification. And oftentimes, this has not been done for these patients, but MYC amplification and MYC re-arrangement are present in basal like carcinoma and known to be one of the initiators of tumor drivers basically for breast cancer. And the other thing that I want to mention about the patient, speaking of the other genomic markers that we had. The patient has tumor mutation burden that is called -- it is intermediate, but really in the high end, it's 9.9 mutations per megabase. So that -- it's important because, as you will see in a -- well, the patient also had PD-L1 expression. So that in terms of the immuno-oncology opportunities for the patient, it's quite [indiscernible] because tumor mutation burden when they are higher than 10 mutations per megabase patients tend to respond better and they are depending on the clinical context TMB of 10 or more can dictate the indication of pembrolizumab specifically, but also the expression of PD-L1 can be used as a biomarker predictive response for immuno-oncology. In this case, the antibody that has been used in IHC is the SP142, which is the FDA-approved test for the molecular [indiscernible] don't want to use [indiscernible] but it's predictable that the PD-L1 by the 22C3 antibody will probably also be positive when you think of the combination of the tumor mutation burden as well. So another immunohistochemistry studies that were done was a pan-tyrosine receptor kinase IHC, which recognized typically -- which recognize and track 1, 2 and 3, mainly or is expected to be a surrogate for those. And when those are detected in immunohistochemistry typically gene fusion detection assay will be best performed to determine which alteration is present rather than having just that result, but it can negative. If we can see the next slide, please.

Do you have the ER/PR receptor?

That's what I'm looking for this patient because we should have had it, trying to find where it was. I think it's a little bit further down. No, we don't have it in here. Let me pull it off. It was HER2 low, that's for sure. No way, we don't have it here. Give me one second. I'm trying to pull out this case specifically.

So while you're doing that pretty much.

Yes, please if you can comment on the case.

So from the genomics standpoint, we know that PTEN expression has been shown to show response to mTOR inhibitor. It works through the mTOR pathway. And that is something to keep in mind as one of the therapies for this patient. Then the RB1 gene mutation may confer that response to CD4/6 inhibition is less or at least shows lack of prevention of progression. That's how they put it in the studies. So we may consider that as not one of the best therapies for this patient, if the patient is ER positive. Of course, with the PD-L1 expression, though, now we do the 2 to 3 expression that is more for pembrolizumab, which is now the FDA-approved drug for triple-negative breast cancers in this country. I would expect it to be positive more than likely, but once we get that input, then we can consider pembrolizumab as one of the options of therapy with or without chemotherapy. So that -- those are all options for this patient. Of course, the ER positivity will change which drugs you would choose, whether it would be hormonal therapy, especially with an elderly patient that might be a better option. So did you find that?

Sure. So when we're looking to see if we find it -- we had a few questions from the audience, and we'll try to address some of these questions.

So there is one question here for this case. The first -- we'll answer the second one first. For this case, the PIK3CA, BRAF, KRAS and pan-TRK were included. Are they additive biomarkers or included in predetermined profile panel? Okay. This is pretty much -- I guess I have to take this one in this regard because it's about the test per se. Well, this test is performed in our laboratory, so the pan-TRK -- this is a type of -- this is a NeoTYPE test provided by our laboratory, which includes those modalities additional to the genomic testing. And they are added on as part of the whole profile for the patient. The other question that was asked is if for patients if we -- if you utilize liquid biopsy testing for breast patients if tissue is not sufficient or not viable. And what markers such as PIK3CA, et cetera, would you be looking in a liquid biopsy for breast cancer patients?

Well, we had this discussion recently, some of our tumor boards and some other advisory boards as to whether we would look at liquid biopsies for breast patients? Or would you look at tissue. I think the thing we came up with was the studies are not adequate with liquid biopsies like we do with lung cancer. But at least the initial testing, we feel should be done with tissue and then maybe subsequent follow-up with blood sample may be reasonable. But I guess if you didn't have tissue available, I'll let Dr. Lopez-Diaz comment on that as to -- and because the tissue, I guess, would also give us some of the other IHC markers, so you would be using it for that anyway, like PD-L1, et cetera. So do you -- can you comment on that question again?

Yes. So well, definitely, of course, the more it seems the merrier, the more information you can gather for a patient, the more information you would have to decide. So liquid biopsy testing, it is something that one could consider if -- this is not my experience. Of course, I'm not a physician, as you all know. But we know from our clients basically what they would typically do as Dr. Jay would do, she oftentimes requires a liquid biopsy testing. And what we've seen from the interactions with our clients and with many others in the field, is that, yes, liquid biopsy testing is often sought after when progression exists typically for -- when the lesions are very difficult to access that is an...

Would you recommend that we do a baseline with the tissue that's available, usually with breast cancers, for example, you may have the original pathology from the breast that you could do some -- would that be necessary? Or not or should we be looking at?

Well, it always depends on the stage of the disease. So if you have a patient presentation or a diagnosis it is more valuable to have tissue plus any liquid biopsy. I think that it's a hard question to answer because whatever you can have is better. So if you cannot have an EC biopsy, and -- but you can have the liquid biopsy only. Is it going to have value? Yes, it will definitely because you will find out alterations that of tumor cells that have been spread to the circulation, is the baseline established by the tissue always expected to match. Studies have shown that there is a high degree of correlation between baseline alterations in the tissue and the DNA that is being spread through the circulation, but that concordance is not 100%. So you can always have discordance and so mutations that were not present at baseline that are present now, and there is an explanation for that, which is the evolution of the -- and the progression of the disease, and vice versa can also happen. So you can lose alterations because certain mutations might have been present in certain [ clone ] that upon treatment might have been basically diminished below the detection level if I given assay. And those studies -- I think we discussed this very extensively in other tumor boards for lung cancer where the wealth of information does exist. But I can tell you also that -- we -- our laboratory and others have test that rely on the detection of alterations in circulation that relate to the initial tumor, and not all alterations will be identical, but there is an expectation of alterations that will match between baseline and the other one. When you think on therapy administration, I think the results are very -- you do have a percentage. I can't remember the exact number. So I don't want to say what is it it's 78% or 95% of correlation between all the mutations that you would find but you will find a correlation between baseline and liquid biopsy, but you will also find new alterations that offer the new opportunity. And if the alterations are there, you don't know if they came from the first tumor that you biopsied? Or if they coming from a different clone that was in a lesion that you did not see at first as it was not part of the biopsy, especially when the tumors involve large masses, there is that phenomenon that we call tumor heterogeneity. That is true, it's not a makeup story by the lab to explain why certain things are not detected in one test but in another are. It definitely happened. If you sequence a tumor studies from the Sanger Institute in the U.K. have shown that lesions, especially bigger lesions about 3 centimeters when they have been tested and that in different tumor types, indeed, breast, pancreas, lungs and colorectal tumors. Up to 5 different sub-biopsies of a tumor might present a number of differentiating alterations that are unique to that tumor. And that is totally normal, and it matches with the expected behavior of cancer. What we typically go by in the molecular diagnostic session is that when an alteration is detected, that alteration is present there. When you cannot see in a given alteration. If you don't see it in the liquid biopsy, maybe the tumor is not spreading cell into circulation. And if you don't see it in the biopsy, but you're seeing it in the liquid -- in blood circulation. Well, maybe it's not -- it was not present in the tumor that you biopsied, but it was present either in another lesion, and this is in breast cancer. There are two typical recurrence sites, as Dr. Jay can speak much better than me. But lung, liver and bone are the preferred sites for metastasis and the liver biopsies, for instance, or the liver lesion very often when they can be tested, they would show some differences. That's where you might most often find differentiating factors. And if those are the driving lesions of the disease that are spreading DNA into circulation, you might find differences with the initial biopsy. Does it have value? And yes, it has.