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Advances in the Management of NETs

Insights From: Heloisa P. Soares, MD, UNM Comprehensive Cancer Center; Jonathan R. Strosberg, MD, Moffitt Cancer Center; Timothy J. Hobday, MD, Mayo Clinic College of Medicine and Science
Published: Thursday, Mar 01, 2018



Transcript: 

Heloisa P. Soares, MD: The treatment of neuroendocrine tumors is very multidisciplinary. We typically have to work very closely with our pathologists because there are several extra questions that we sometimes don’t get in the initial pathology report. Then we have to work very closely with radiologists because going over scans from a patient with a neuroendocrine tumor is not as simple as one would think. Finally, we have to work very closely with our surgeons because, in many cases, even if a patient has what’s called stage 4 disease, or disease that has spread to other organs, we are still going to be thinking about surgery. So, this is a very multidisciplinary approach.

Then, obviously, we take a lot of input from our interventional radiologists and from our gastroenterologists. They are all part of the team. And I haven’t even mentioned that for patients who have carcinoid syndrome, they’re at high risk for carcinoid heart disease. Therefore, including the cardiologist, very early on in treatment, is important. For patients who have hereditary syndrome, such as MEN1 (multiple endocrine neoplasia type 1), you might have to involve an endocrinologist and a geneticist very early on in treatment as well. Because of all of that, I think having a very well established multidisciplinary treatment team is essential for treating patients with neuroendocrine tumors.

In terms of recent advances in neuroendocrine tumors, it has been very busy in the past few years—from improving the care of patients from a tumor control standpoint to symptomatic control. If I go back, a few years ago, we had the approval of everolimus for neuroendocrine tumors. In the past, it has been approved for pancreatic neuroendocrine tumors. But most recently, it was approved for tumor control in other neuroendocrine tumors, especially in the gastrointestinal tract and lung.

Most recently, with data from the NETTER-1 study, they’re looking to PRRT (peptide receptor radionuclide therapy) for patients with midgut neuroendocrine tumors. We are very interested in the improvement in progression-free survival, and we are waiting for the FDA approval for that indication, at least in midgut tumor patients. And in terms of symptom control, lanreotide was most recently approved for the treatment of carcinoid syndrome, in addition to tumor progression. And we have telotristat, which has been approved for control of diarrhea that has been refractory to somatostatin analogs.

In terms of imaging improvements, the most exciting things that have happened in the past few years are improvements in techniques with the PET/CT scan and a different radiolabeled approach, which is commercially known as Netspot. Or we also say gallium 68. It has been shown to really improve detection and the sensitivity of finding neuroendocrine tumors, compared with Octreoscan, for example. That’s very exciting. Hopefully, many centers in the United States will be offering that soon.

Timothy J. Hobday, MD: Multidisciplinary care of patients with neuroendocrine tumors has continued to improve markedly over the past decade. We were fortunate to have some new approvals, especially in the United States, either recently or forthcoming, that’ll greatly assist in our care of these patients. Telotristat, which is a first-in-class medication to help palliate carcinoid syndrome, was recently approved. This may help patients with carcinoid syndrome who are suffering from diarrhea or flushing that’s not otherwise controlled with the somatostatin analog.

Other recent advances include lanreotide. This is a somatostatin analog. It complements and perhaps overlaps with octreotide, which has been approved and used for neuroendocrine tumors for many years. We anticipate the approval of peptide receptor radiotherapy in the United States. We are still waiting, with great anticipation, to see whether this will be approved for midgut neuroendocrine tumors only, which was the population treated in the NETTER-1 trial—the phase III definitive trial of this treatment modality in the United States. Or whether the approval will be more expanded to patients with well-differentiated neuroendocrine tumors of other primary sites, as long as they have somatostatin receptor expression. How this approval comes from the FDA will greatly affect our practice and our clinical research in the coming years.

I think the other great advance, over the past 3 to 5 years, has been the explosion in the basic science in understanding neuroendocrine tumors—from genomic profiling to looking at the microenvironment (as it might pertain to the use of immunotherapies) to global collaboration and communication in the basic sciences (as it pertains to the biology of neuroendocrine tumors). So, I anticipate great clinical advances coming from that in the next several years.

Jonathan R. Strosberg, MD: It’s great that we have new systemic treatments for this disease. Until recently, there were very few—other than somatostatin analogs. I think it’s important, though, to remember that neuroendocrine tumor treatment remains very complicated. Many patients have liver-only disease. Sometimes, it’s resectable. Sometimes the progression is exclusively in the liver, in which case either surgery or liver embolization can remain a very important part of patients’ treatment. There are many cases where patients remain well controlled, except for growth in maybe 1 or 2 tumors. In this case, locoregional treatments such as surgery or radiation can continue to be very important. So, I think it’s critical that we don’t move to a paradigm where we’re just shifting from one systemic treatment to another systemic treatment without actually looking at the scans and figuring out exactly what’s going on.

Transcript Edited for Clarity 
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Transcript: 

Heloisa P. Soares, MD: The treatment of neuroendocrine tumors is very multidisciplinary. We typically have to work very closely with our pathologists because there are several extra questions that we sometimes don’t get in the initial pathology report. Then we have to work very closely with radiologists because going over scans from a patient with a neuroendocrine tumor is not as simple as one would think. Finally, we have to work very closely with our surgeons because, in many cases, even if a patient has what’s called stage 4 disease, or disease that has spread to other organs, we are still going to be thinking about surgery. So, this is a very multidisciplinary approach.

Then, obviously, we take a lot of input from our interventional radiologists and from our gastroenterologists. They are all part of the team. And I haven’t even mentioned that for patients who have carcinoid syndrome, they’re at high risk for carcinoid heart disease. Therefore, including the cardiologist, very early on in treatment, is important. For patients who have hereditary syndrome, such as MEN1 (multiple endocrine neoplasia type 1), you might have to involve an endocrinologist and a geneticist very early on in treatment as well. Because of all of that, I think having a very well established multidisciplinary treatment team is essential for treating patients with neuroendocrine tumors.

In terms of recent advances in neuroendocrine tumors, it has been very busy in the past few years—from improving the care of patients from a tumor control standpoint to symptomatic control. If I go back, a few years ago, we had the approval of everolimus for neuroendocrine tumors. In the past, it has been approved for pancreatic neuroendocrine tumors. But most recently, it was approved for tumor control in other neuroendocrine tumors, especially in the gastrointestinal tract and lung.

Most recently, with data from the NETTER-1 study, they’re looking to PRRT (peptide receptor radionuclide therapy) for patients with midgut neuroendocrine tumors. We are very interested in the improvement in progression-free survival, and we are waiting for the FDA approval for that indication, at least in midgut tumor patients. And in terms of symptom control, lanreotide was most recently approved for the treatment of carcinoid syndrome, in addition to tumor progression. And we have telotristat, which has been approved for control of diarrhea that has been refractory to somatostatin analogs.

In terms of imaging improvements, the most exciting things that have happened in the past few years are improvements in techniques with the PET/CT scan and a different radiolabeled approach, which is commercially known as Netspot. Or we also say gallium 68. It has been shown to really improve detection and the sensitivity of finding neuroendocrine tumors, compared with Octreoscan, for example. That’s very exciting. Hopefully, many centers in the United States will be offering that soon.

Timothy J. Hobday, MD: Multidisciplinary care of patients with neuroendocrine tumors has continued to improve markedly over the past decade. We were fortunate to have some new approvals, especially in the United States, either recently or forthcoming, that’ll greatly assist in our care of these patients. Telotristat, which is a first-in-class medication to help palliate carcinoid syndrome, was recently approved. This may help patients with carcinoid syndrome who are suffering from diarrhea or flushing that’s not otherwise controlled with the somatostatin analog.

Other recent advances include lanreotide. This is a somatostatin analog. It complements and perhaps overlaps with octreotide, which has been approved and used for neuroendocrine tumors for many years. We anticipate the approval of peptide receptor radiotherapy in the United States. We are still waiting, with great anticipation, to see whether this will be approved for midgut neuroendocrine tumors only, which was the population treated in the NETTER-1 trial—the phase III definitive trial of this treatment modality in the United States. Or whether the approval will be more expanded to patients with well-differentiated neuroendocrine tumors of other primary sites, as long as they have somatostatin receptor expression. How this approval comes from the FDA will greatly affect our practice and our clinical research in the coming years.

I think the other great advance, over the past 3 to 5 years, has been the explosion in the basic science in understanding neuroendocrine tumors—from genomic profiling to looking at the microenvironment (as it might pertain to the use of immunotherapies) to global collaboration and communication in the basic sciences (as it pertains to the biology of neuroendocrine tumors). So, I anticipate great clinical advances coming from that in the next several years.

Jonathan R. Strosberg, MD: It’s great that we have new systemic treatments for this disease. Until recently, there were very few—other than somatostatin analogs. I think it’s important, though, to remember that neuroendocrine tumor treatment remains very complicated. Many patients have liver-only disease. Sometimes, it’s resectable. Sometimes the progression is exclusively in the liver, in which case either surgery or liver embolization can remain a very important part of patients’ treatment. There are many cases where patients remain well controlled, except for growth in maybe 1 or 2 tumors. In this case, locoregional treatments such as surgery or radiation can continue to be very important. So, I think it’s critical that we don’t move to a paradigm where we’re just shifting from one systemic treatment to another systemic treatment without actually looking at the scans and figuring out exactly what’s going on.

Transcript Edited for Clarity 
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