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Precision Oncology in Advanced Pancreatic Cancer

Panelists: John L. Marshall, MD, Georgetown University; George Kim, MD, 21st Century Oncology; Kabir Mody, MD, Mayo Clinic Cancer Center; Eileen M. O'Reilly, MD, Memorial Sloan Kettering Cancer Center; Tanios S. Bekaii-Saab, MD, Mayo Clinic Cancer Center
Published: Tuesday, Jul 24, 2018



Transcript: 

John L. Marshall, MD: Hello and thank you for joining this OncLive® Peer Exchange® titled “Advanced Pancreatic Cancer: The Road to Personalized Care.” Pancreatic cancer is a disease with both a high mortality rate and increasing incidence. Thus, there is a critical need to develop new treatment options for patients with advanced disease. We are beginning to make progress by refining the use of combination chemotherapy and new strategies for sequencing therapy. We are now entering an era where we are learning more about molecular differences and driving mechanisms among pancreatic cancers, with the hope of identifying personalized strategies for patient subsets. For the community oncologist, it’s more important than ever to keep up with the new research and understand the options for clinical trials. In this OncLive® Peer Exchange®, I am joined by an amazing panel of experts in the field of gastrointestinal oncology. Together we’re going to work to provide you with a perspective on recent advances and what they mean to the care of your patients for weeks ahead.

I am Dr. John Marshall, and I am chief of the Division of Hematology/Oncology at MedStar Georgetown University Hospital; professor of medicine and oncology at Lombardi Comprehensive Cancer Center Georgetown University; and the director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancer in Washington, DC. Participating with us today are not only distinguished panelists but really very good friends. Dr. George Kim, a GI oncologist in Jacksonville, Florida. George, welcome. Thanks for joining us. Dr. Kabir Mody, assistant professor of medicine and consultant for the Division of Medical Oncology GI Malignancy Program and the co-chair of the Mayo Clinic Hepatobiliary Disease Group in Jacksonville, Florida. Kabir, welcome. Dr. Eileen O’Reilly, attending physician and member at Memorial Sloan Kettering Cancer Center in New York, New York, and associate director of the David M. Rubenstein Center for Pancreas cancer. Eileen, welcome. And last but not least, Dr. Tanios Bekaii-Saab, professor, Mayo Clinic College of Medicine and Science Program, and co-leader of GI Cancer at the Mayo Clinic Cancer Center in Phoenix, Arizona. Toni, welcome.

Eileen, we’re going to let you give us a start here. This whole ASCO, where we are today, is themed around precision medicine, personalized medicine, molecular characteristics. Can you give us a high level look of where we are in molecular medicine; maybe some data around molecular medicine in pancreatic cancer?

Eileen M. O’Reilly, MD: John, this is a very exciting topic in pancreas cancer. We’re now beginning to be able to refine treatment choices for patients. To give you a couple examples of this; the BRCA subgroup; people with germline BRCA, it’s about 6% to 7% of people with unselected pancreas cancer. We now have unequivocal evidence, to support the use of platinum-based therapies. In the pretreated setting, a role selectively for PARP inhibitors; we’re also looking at PARP inhibitors for maintenance therapy, so that’s one group. A broader group of patients with homologous repair defects is beginning to be defined, so learning to know whether patients with somatic BRCA mutations, with ATM, with CHK2 mutations; whether these will also benefit from that strategy.

John L. Marshall, MD: George, you and I were talking about this. Do we know how to measure this BRCA-ness or HRD, as Eileen is talking about?

George P. Kim, MD: Yes, I’m a little critical of this. Eileen and I have had a lot of discussions this weekend, but I don’t know. I think we need to do more work. Obviously, the germline mutations are there and that’s pretty clear.

John L. Marshall, MD: So, good strong family history, but ultimately molecular testing to confirm, that, right?

George P. Kim, MD: Yes, and we need to validate it. It’s like every other predictive marker in GI cancer. We need to do a little more work, a little more work, a little more work, and really nail down what are the aberrations that are important.

John L. Marshall, MD: There are a lot of genes in the literature around BRCA-ness and the whole HRD pathway. We did a broad look at some big gene data sets that we had and found that about half of those that were in the medical literature aren’t ever expressed in actual patients, so they become irrelevant ways of measuring this. Would you say next-generation sequencing is what we need to be doing to figure this out?

Eileen M. O’Reilly, MD: I think so. There is no clear definition of what’s actionable in pancreas cancer yet, beyond a few very specified events. The other key one to note; even though it’s rare, is the 1% to 2% of patients with mismatch repair deficient, or MSI-high pancreas cancer. Work from our group has suggested that they mostly are people with germline Lynch syndrome. We see relatively few somatic mismatch repair deficient malignancies, so I think we have to keep that group in mind. The other approach to think about; with regard to next-generation sequencing; is what trial options there are for patients. If there’s a BRAF mutation, occasionally we’ll pick that up, patient with an NTRK fusion, there are actionable events.

John L. Marshall, MD: There are a lot of these 1, or less than 1% items that are coming forward where we have really cool drugs. I’m just betting that the Mayo Clinic patient is very interested in immunotherapy. Kabir, are you getting a lot of these folks coming in and saying, “I’ve got pancreas cancer, I want one of these new immunotherapy drugs”?

Kabir Mody, MD: Yes, absolutely.

John L. Marshall, MD: How are you dealing with that?

Kabir Mody, MD: You have to share with them at least the existing data, and do some education on their part because they’re hearing this from all sorts of sources outside, without the knowledge of what types of cancer they’re talking about in that literature; those results that are being advertised and that sort of thing.

John L. Marshall, MD: Don’t you wish we could get paid for a level of visit for explaining away treatments that aren’t possible. There is no level 6 as far as I’ve found so far.

Kabir Mody, MD: One thing that is notable is that we’re seeing a little bit more in the way of subtyping of the disease, whether it’s genomic or histologic. The COMPASS study looked at classic versus basal cell subtyping, and then we had Andrew Biankin’s group talking about 4 different genomically based subtypes. But, those are a little bit away from the clinic obviously, because we don’t have a practical assay that is translated to clinical practice yet, but we’re getting there, hopefully.

Transcript Edited for Clarity

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Transcript: 

John L. Marshall, MD: Hello and thank you for joining this OncLive® Peer Exchange® titled “Advanced Pancreatic Cancer: The Road to Personalized Care.” Pancreatic cancer is a disease with both a high mortality rate and increasing incidence. Thus, there is a critical need to develop new treatment options for patients with advanced disease. We are beginning to make progress by refining the use of combination chemotherapy and new strategies for sequencing therapy. We are now entering an era where we are learning more about molecular differences and driving mechanisms among pancreatic cancers, with the hope of identifying personalized strategies for patient subsets. For the community oncologist, it’s more important than ever to keep up with the new research and understand the options for clinical trials. In this OncLive® Peer Exchange®, I am joined by an amazing panel of experts in the field of gastrointestinal oncology. Together we’re going to work to provide you with a perspective on recent advances and what they mean to the care of your patients for weeks ahead.

I am Dr. John Marshall, and I am chief of the Division of Hematology/Oncology at MedStar Georgetown University Hospital; professor of medicine and oncology at Lombardi Comprehensive Cancer Center Georgetown University; and the director of the Otto J. Ruesch Center for the Cure of Gastrointestinal Cancer in Washington, DC. Participating with us today are not only distinguished panelists but really very good friends. Dr. George Kim, a GI oncologist in Jacksonville, Florida. George, welcome. Thanks for joining us. Dr. Kabir Mody, assistant professor of medicine and consultant for the Division of Medical Oncology GI Malignancy Program and the co-chair of the Mayo Clinic Hepatobiliary Disease Group in Jacksonville, Florida. Kabir, welcome. Dr. Eileen O’Reilly, attending physician and member at Memorial Sloan Kettering Cancer Center in New York, New York, and associate director of the David M. Rubenstein Center for Pancreas cancer. Eileen, welcome. And last but not least, Dr. Tanios Bekaii-Saab, professor, Mayo Clinic College of Medicine and Science Program, and co-leader of GI Cancer at the Mayo Clinic Cancer Center in Phoenix, Arizona. Toni, welcome.

Eileen, we’re going to let you give us a start here. This whole ASCO, where we are today, is themed around precision medicine, personalized medicine, molecular characteristics. Can you give us a high level look of where we are in molecular medicine; maybe some data around molecular medicine in pancreatic cancer?

Eileen M. O’Reilly, MD: John, this is a very exciting topic in pancreas cancer. We’re now beginning to be able to refine treatment choices for patients. To give you a couple examples of this; the BRCA subgroup; people with germline BRCA, it’s about 6% to 7% of people with unselected pancreas cancer. We now have unequivocal evidence, to support the use of platinum-based therapies. In the pretreated setting, a role selectively for PARP inhibitors; we’re also looking at PARP inhibitors for maintenance therapy, so that’s one group. A broader group of patients with homologous repair defects is beginning to be defined, so learning to know whether patients with somatic BRCA mutations, with ATM, with CHK2 mutations; whether these will also benefit from that strategy.

John L. Marshall, MD: George, you and I were talking about this. Do we know how to measure this BRCA-ness or HRD, as Eileen is talking about?

George P. Kim, MD: Yes, I’m a little critical of this. Eileen and I have had a lot of discussions this weekend, but I don’t know. I think we need to do more work. Obviously, the germline mutations are there and that’s pretty clear.

John L. Marshall, MD: So, good strong family history, but ultimately molecular testing to confirm, that, right?

George P. Kim, MD: Yes, and we need to validate it. It’s like every other predictive marker in GI cancer. We need to do a little more work, a little more work, a little more work, and really nail down what are the aberrations that are important.

John L. Marshall, MD: There are a lot of genes in the literature around BRCA-ness and the whole HRD pathway. We did a broad look at some big gene data sets that we had and found that about half of those that were in the medical literature aren’t ever expressed in actual patients, so they become irrelevant ways of measuring this. Would you say next-generation sequencing is what we need to be doing to figure this out?

Eileen M. O’Reilly, MD: I think so. There is no clear definition of what’s actionable in pancreas cancer yet, beyond a few very specified events. The other key one to note; even though it’s rare, is the 1% to 2% of patients with mismatch repair deficient, or MSI-high pancreas cancer. Work from our group has suggested that they mostly are people with germline Lynch syndrome. We see relatively few somatic mismatch repair deficient malignancies, so I think we have to keep that group in mind. The other approach to think about; with regard to next-generation sequencing; is what trial options there are for patients. If there’s a BRAF mutation, occasionally we’ll pick that up, patient with an NTRK fusion, there are actionable events.

John L. Marshall, MD: There are a lot of these 1, or less than 1% items that are coming forward where we have really cool drugs. I’m just betting that the Mayo Clinic patient is very interested in immunotherapy. Kabir, are you getting a lot of these folks coming in and saying, “I’ve got pancreas cancer, I want one of these new immunotherapy drugs”?

Kabir Mody, MD: Yes, absolutely.

John L. Marshall, MD: How are you dealing with that?

Kabir Mody, MD: You have to share with them at least the existing data, and do some education on their part because they’re hearing this from all sorts of sources outside, without the knowledge of what types of cancer they’re talking about in that literature; those results that are being advertised and that sort of thing.

John L. Marshall, MD: Don’t you wish we could get paid for a level of visit for explaining away treatments that aren’t possible. There is no level 6 as far as I’ve found so far.

Kabir Mody, MD: One thing that is notable is that we’re seeing a little bit more in the way of subtyping of the disease, whether it’s genomic or histologic. The COMPASS study looked at classic versus basal cell subtyping, and then we had Andrew Biankin’s group talking about 4 different genomically based subtypes. But, those are a little bit away from the clinic obviously, because we don’t have a practical assay that is translated to clinical practice yet, but we’re getting there, hopefully.

Transcript Edited for Clarity
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Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Integrating Novel Targeted Treatment Strategies to Advance Pancreatic Cancer CareNov 30, 20181.0
Medical Crossfire®: Navigating Treatment Decisions in Pancreatic Cancer: Key QuestionsJun 29, 20191.5
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