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Current Practice With Molecular Testing in Pancreatic Cancer

Panelists: Johanna Bendell, MD, Sarah Cannon Research Institute; Eileen O’Reilly, MD, Memorial Sloan-Kettering Cancer Center; John Marshall, MD, Ruesch Cancer Center at the Lombardi Comprehensive Cancer Center; George Kim, MD, University of Florida Health Oncology; Caio Max S. Rocha Lima, MD, Gibbs Cancer Center
Published Online: Friday, Feb 17, 2017



Transcript:

Johanna Bendell, MD:
And so, the buzz words in cancer care nowadays, besides immunotherapy—which we will get to—are “molecular profiling.” So, Caio, is there a role for molecular profiling for patients with pancreas cancer?

Caio Max S. Rocha Lima, MD: That’s an excellent question, and I think it is an unmet need. The problem is that we get them, and many times, we do not know what to do with them. In our institution, we routinely perform on patients who have good performance status and are not hospice candidates. We send for next-generation sequencing in all of them, and we are doing that prospectively and longitudinally. And most of those reports will come up with the KRAS mutation in codon 12, and we do not have a way to really target RAS today.

Having said that, there is a set of patients, maybe about 10%, that have BRCA mutations, where there may be future therapeutic opportunities in ongoing clinical trials that we are going to get to. And outside of the next-generation sequencing, there are some data in the immunotherapy world about the potential of microsatellite instability that we’re also going to get to.

Johanna Bendell, MD: It’s not just colon cancer is it?

Caio Max S. Rocha Lima, MD: It’s not.

John Marshall, MD: Johanna, could I jump in? I know I do this all the time, but part of the barrier is—and I know everyone on the table shares this—this adequate tissue. And so, often we’re making a diagnosis off 2 cells or a couple of atypical cells. The challenge on molecular profiling is getting enough tissue, and I don’t. So, we want to do this, but I think one of the problems is we haven’t been able to get enough.

Johanna Bendell, MD: Yes. Big education effort around getting core biopsies and not doing the fine needle aspirations, even on endoscopic ultrasound. Do you guys use a lot of that?

Eileen O’Reilly, MD: Yes, absolutely. And I think there has been a big change in the field, at least a move in the direction of not living with FNAs (fine needle aspirates)—which was the standard paradigm for many years—trying to do cores, and, in particular, trying to biopsy metastatic sites so we have less of an issue in terms of adequate tissue and an ability to profile. But I think the question you raise is really an important practical one. We know we can do this, and we can do this reproducibly for a lot of patients. But is there added value? I think we’re, to a degree, struggling with this in pancreas cancer, and I think we should maybe get the group’s opinion on this because it’s a very topical question and everybody wants it.

George Kim, MD: So, I agree with John that we do need to get more tissue. It’s almost unethical that we keep going forward and putting patients on trials where we don’t have any idea. Is there a chance that they may benefit? And so, it’s almost unethical to keep going forward without getting tissue. And so there are issues of whether we should biopsy. I would think we should biopsy. We were actually starting programs to do rebiopsies—so, after a patient progresses, re-biopsying them and trying to figure out how the tumor has changed. We keep hearing, in pancreas cancer, that it’s so heterogeneous, there are so many mutations that are involved. We just need to be more dynamic.

Johanna Bendell, MD: So, for the average practicing oncologist that’s out there, what are they looking for potentially baseline? It sounds like we’re agreeing upon BRCA, and it sounds like we’re agreeing upon microsatellite instability, because these patients may be treated differently than the typical patients.

Eileen O’Reilly, MD: And I think taking a good history is important, just understanding whether the person or the family is at risk for this disease. There may be implications beyond the person themselves, and that’s in particular with any germline findings in BRCA. There needs to be a recognition that it happens across all subgroups of people with this disease, and it may be anywhere from 5% to 8%, maybe a little bit less or a little higher. But that’s potentially very important when we get some clues in terms of screening for healthy carriers in those families as well.

Johanna Bendell, MD: Yes. And I think that for patients who potentially had access to clinical trials, having the next-generation sequencing may give them some more options in terms of treatment. That’s when you can talk about maybe something like serial biopsies. Leading into that, clinical trials, George, how do you feel about those for patients with pancreas cancer?

George Kim, MD: Well, it’s obvious that we have more work to do, and we do have a couple standards now: FOLFIRINOX and Abraxane/gemcitabine. But we’ve got a lot of work to do, and thankfully, there is a trial out there with a lot of interest: the PEGPH20 study looking at the hyaluronidase inhibitor—that’s going to be an interesting trial. There are some data coming forward that was presented earlier this month that showed some promising results. So, that’s one study that I’m looking forward to seeing the results of. Unfortunately, a lot of trials have failed. So, again, we just have a lot of work to do. We’ve got to get the trials open, we’ve got to get the trials available, we have to work through the Intergroup, and we have to encourage patients to go on the studies.

John Marshall, MD: I think this group of patients, unlike many of our GI patients, are really interested in trials. They have a very high acceptance rate, if you’ve got one. Because somehow they know that we’re looking for something. In colon cancer, they may take it or leave it, but don’t you all think this, too?

Eileen O’Reilly, MD: I think so, but the hugely important message is the need for trials, and this is how we learn quickly in terms of successes and failures. It has mostly been failures to date, but the more people we get on studies, the better that we can improve outcomes. So, I think it’s an extremely important message. And yes, I think receptivity is there—perhaps more so than before—particularly in the second-and-third-line settings when options are becoming more narrow. Patients and families are very open to studies.

John Marshall, MD:
And I can’t help but pitch the PanCAN-centered studies that are going on. It’s really one of the best support groups out there in our space in that they’re funding research and they support education for patients around clinical trials. And there is now a nationwide study that couples our discussion of biopsies, molecular profile, and treatment assignment for second-line patients. And so, we need to get as many patients as we can into that kind of flow.

Johanna Bendell, MD: Yes, all of these clinical trial-matching servers are not only through PanCAN, but others as well could help get both doctors and patient access to these studies.

George Kim, MD: A lot of courage by PanCAN to take that on. We’ve been asking for someone to do that for a long time. It’s just a lot of courage for them to do that today.

Caio Max S. Rocha Lima, MD: I’d also like to emphasize that not only on the therapeutic side for the disease itself, but also on the palliative side. In our institution, we have plans of opened trials for pain control. What is the role of celiac plexus procedures in pancreatic cancer? Also, getting to gastric hepatitis, there are opportunities for trials in that setting. And cachexia was, for a period of time, investigated, and some molecules were developed that did not pan out. But it is so prevalent in pancreatic cancer, I think we should rekindle that venue.

Eileen O’Reilly, MD: I’d just like to add to the discussion on clinical trials this new model of doing clinical trials. There are a couple of examples of this: Precision Promise in the United States and PRECISION-Panc in the UK, which are supported by advocacy organizations in partnership with pharma and partnership with patients and researchers. This may prove to be a more efficient model for doing clinical trials quickly. So, we’ll see if we can move the field forward with the right resources. And I think there is recognition from every level. In Congress, funding is increased for pancreas cancer, and we know this huge public health challenge is looming with this disease compared to some other malignancies.

Transcript Edited for Clarity

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Transcript:

Johanna Bendell, MD:
And so, the buzz words in cancer care nowadays, besides immunotherapy—which we will get to—are “molecular profiling.” So, Caio, is there a role for molecular profiling for patients with pancreas cancer?

Caio Max S. Rocha Lima, MD: That’s an excellent question, and I think it is an unmet need. The problem is that we get them, and many times, we do not know what to do with them. In our institution, we routinely perform on patients who have good performance status and are not hospice candidates. We send for next-generation sequencing in all of them, and we are doing that prospectively and longitudinally. And most of those reports will come up with the KRAS mutation in codon 12, and we do not have a way to really target RAS today.

Having said that, there is a set of patients, maybe about 10%, that have BRCA mutations, where there may be future therapeutic opportunities in ongoing clinical trials that we are going to get to. And outside of the next-generation sequencing, there are some data in the immunotherapy world about the potential of microsatellite instability that we’re also going to get to.

Johanna Bendell, MD: It’s not just colon cancer is it?

Caio Max S. Rocha Lima, MD: It’s not.

John Marshall, MD: Johanna, could I jump in? I know I do this all the time, but part of the barrier is—and I know everyone on the table shares this—this adequate tissue. And so, often we’re making a diagnosis off 2 cells or a couple of atypical cells. The challenge on molecular profiling is getting enough tissue, and I don’t. So, we want to do this, but I think one of the problems is we haven’t been able to get enough.

Johanna Bendell, MD: Yes. Big education effort around getting core biopsies and not doing the fine needle aspirations, even on endoscopic ultrasound. Do you guys use a lot of that?

Eileen O’Reilly, MD: Yes, absolutely. And I think there has been a big change in the field, at least a move in the direction of not living with FNAs (fine needle aspirates)—which was the standard paradigm for many years—trying to do cores, and, in particular, trying to biopsy metastatic sites so we have less of an issue in terms of adequate tissue and an ability to profile. But I think the question you raise is really an important practical one. We know we can do this, and we can do this reproducibly for a lot of patients. But is there added value? I think we’re, to a degree, struggling with this in pancreas cancer, and I think we should maybe get the group’s opinion on this because it’s a very topical question and everybody wants it.

George Kim, MD: So, I agree with John that we do need to get more tissue. It’s almost unethical that we keep going forward and putting patients on trials where we don’t have any idea. Is there a chance that they may benefit? And so, it’s almost unethical to keep going forward without getting tissue. And so there are issues of whether we should biopsy. I would think we should biopsy. We were actually starting programs to do rebiopsies—so, after a patient progresses, re-biopsying them and trying to figure out how the tumor has changed. We keep hearing, in pancreas cancer, that it’s so heterogeneous, there are so many mutations that are involved. We just need to be more dynamic.

Johanna Bendell, MD: So, for the average practicing oncologist that’s out there, what are they looking for potentially baseline? It sounds like we’re agreeing upon BRCA, and it sounds like we’re agreeing upon microsatellite instability, because these patients may be treated differently than the typical patients.

Eileen O’Reilly, MD: And I think taking a good history is important, just understanding whether the person or the family is at risk for this disease. There may be implications beyond the person themselves, and that’s in particular with any germline findings in BRCA. There needs to be a recognition that it happens across all subgroups of people with this disease, and it may be anywhere from 5% to 8%, maybe a little bit less or a little higher. But that’s potentially very important when we get some clues in terms of screening for healthy carriers in those families as well.

Johanna Bendell, MD: Yes. And I think that for patients who potentially had access to clinical trials, having the next-generation sequencing may give them some more options in terms of treatment. That’s when you can talk about maybe something like serial biopsies. Leading into that, clinical trials, George, how do you feel about those for patients with pancreas cancer?

George Kim, MD: Well, it’s obvious that we have more work to do, and we do have a couple standards now: FOLFIRINOX and Abraxane/gemcitabine. But we’ve got a lot of work to do, and thankfully, there is a trial out there with a lot of interest: the PEGPH20 study looking at the hyaluronidase inhibitor—that’s going to be an interesting trial. There are some data coming forward that was presented earlier this month that showed some promising results. So, that’s one study that I’m looking forward to seeing the results of. Unfortunately, a lot of trials have failed. So, again, we just have a lot of work to do. We’ve got to get the trials open, we’ve got to get the trials available, we have to work through the Intergroup, and we have to encourage patients to go on the studies.

John Marshall, MD: I think this group of patients, unlike many of our GI patients, are really interested in trials. They have a very high acceptance rate, if you’ve got one. Because somehow they know that we’re looking for something. In colon cancer, they may take it or leave it, but don’t you all think this, too?

Eileen O’Reilly, MD: I think so, but the hugely important message is the need for trials, and this is how we learn quickly in terms of successes and failures. It has mostly been failures to date, but the more people we get on studies, the better that we can improve outcomes. So, I think it’s an extremely important message. And yes, I think receptivity is there—perhaps more so than before—particularly in the second-and-third-line settings when options are becoming more narrow. Patients and families are very open to studies.

John Marshall, MD:
And I can’t help but pitch the PanCAN-centered studies that are going on. It’s really one of the best support groups out there in our space in that they’re funding research and they support education for patients around clinical trials. And there is now a nationwide study that couples our discussion of biopsies, molecular profile, and treatment assignment for second-line patients. And so, we need to get as many patients as we can into that kind of flow.

Johanna Bendell, MD: Yes, all of these clinical trial-matching servers are not only through PanCAN, but others as well could help get both doctors and patient access to these studies.

George Kim, MD: A lot of courage by PanCAN to take that on. We’ve been asking for someone to do that for a long time. It’s just a lot of courage for them to do that today.

Caio Max S. Rocha Lima, MD: I’d also like to emphasize that not only on the therapeutic side for the disease itself, but also on the palliative side. In our institution, we have plans of opened trials for pain control. What is the role of celiac plexus procedures in pancreatic cancer? Also, getting to gastric hepatitis, there are opportunities for trials in that setting. And cachexia was, for a period of time, investigated, and some molecules were developed that did not pan out. But it is so prevalent in pancreatic cancer, I think we should rekindle that venue.

Eileen O’Reilly, MD: I’d just like to add to the discussion on clinical trials this new model of doing clinical trials. There are a couple of examples of this: Precision Promise in the United States and PRECISION-Panc in the UK, which are supported by advocacy organizations in partnership with pharma and partnership with patients and researchers. This may prove to be a more efficient model for doing clinical trials quickly. So, we’ll see if we can move the field forward with the right resources. And I think there is recognition from every level. In Congress, funding is increased for pancreas cancer, and we know this huge public health challenge is looming with this disease compared to some other malignancies.

Transcript Edited for Clarity
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