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Maintenance Therapy in Metastatic 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
Published: Friday, Aug 31, 2018



Transcript: 

Tanios S. Bekaii-Saab, MD: This was the study with FOLFIRINOX into progression. It was limited to 6 months; that’s how the French designed it. Then FOLFIRINOX with maintenance therapy, roughly 4 months, going to 5-FU with reintroduction of the oxaliplatin. There’s a third arm I’m not going to spend much time talking about because I don’t think it has as much relevance in this discussion.

But this study was interesting because it showed essentially that—I think the way I interpreted it, and also what my colleagues think— the maintenance strategy is feasible. That we can go from an induction-intense 3-month FOLFIRINOX, and then deescalate to infusional 5-FU. The one problem with this study was that, although the outcomes were very similar, the toxicities seemed to be higher when you do what I call the stop-and-go of pancreas cancer—FOLFIRINOX, 5-FU and reintroduce oxaliplatin—and it appears that the reintroduction of the oxaliplatin increased the risk of neuropathy. Now, this is not colon cancer where 5-FU can maintain you for 6 months to a year, where the neuropathy of oxaliplatin may be a grade 1. These are patients that get oxaliplatin reintroduced within 3 months, and that may explain essentially the increased risk of neuropathy.

I think, at least the way I interpret this, is FOLFIRINOX followed by 5-FU makes sense, and we should consider it very strongly for most of our patients, if not all. The question that remains is, do we really need to introduce oxaliplatin or should we switch to another regimen at that point?

Eileen M. O’Reilly, MD: Can I give you another take on that? It’s that I would have loved to have seen them ask the question of FOLFIRI as the maintenance.

Kabir Mody, MD: Yes, absolutely.

Eileen M. O’Reilly, MD: Because I think that combination may control the disease for longer and allow you to continue to hold off the oxaliplatin.

Tanios S. Bekaii-Saab, MD: And perhaps reintroduce the oxaliplatin once the stone’s done. Absolutely I agree.

John L. Marshall, MD: I think a lot of this is very important, but it’s a subtlety for us as disease experts. I think that what I’m seeing time and again by our community partners is they just keep going until the patient pops. Whether it’s side effects or fatigue or a treat-to-progression kind of mentality. The theme in GI, at least in colorectal and pancreas, what we’re seeing is that after that induction, it is logical to back off. We are wrestling about what backing off looks like, but that should be a theme. If you’re responding and you’re getting on top of the disease, you need to develop a strategy for backing off.

Eileen M. O’Reilly, MD: I think we have now a reasonable level of evidence to support this and to continue to explore this, because we really need data to help define; but yes, I think so.

George P. Kim, MD: It allows us to take a break. Again, we’re still giving chemotherapy but we’re just not giving them oxaliplatin, so I think it’s useful. But you have to talk to the patient every so often. What does the patient want?

John L. Marshall, MD: Especially if you’re going to bill them.

George P. Kim, MD: Many patients want to keep at it. Some patients have a lot of side effects. They have all the fatigue and the neuropathy, they want to back off, they want to go to Hawaii. Some people don’t want to keep going.

John L. Marshall, MD: But some of that is how we present it at the beginning I think, too. If you go into that first visit with a strategy of saying, “We’re going to get you off the ledge and then see if we can back this off,” I think that patient understands that’s the norm. Versus this culture of the battle of cancer and the war on cancer.

John L. Marshall, MD: We have to keep fighting and there has to be suffering. I always reflect on the long game for those patients—I’m not worried about this Christmas, I’m worried about next Christmas. That gives them a little perspective of what if you say you want to live forever? Well could you keep taking this regimen forever, or do we need to take some breaks?

Tanios S. Bekaii-Saab, MD: Again, it’s the sprint versus marathon analogy that amazingly enough, we’re having these discussions.

John L. Marshall, MD: Yes, it’s a good problem.

Tanios S. Bekaii-Saab, MD: We should be happy that we’re having these discussions and we’re thinking about these issues in pancreas cancer. That means we’re making a much bigger difference.

Kabir Mody, MD: But again, to emphasize the importance of our palliative care colleagues, because they do a very good job of framing that mindset you’re talking about.

Tanios S. Bekaii-Saab, MD: However, I do think that oncologists are great palliative care doctors when they take the time to do it.

Kabir Mody, MD: I agree, yes.

Tanios S. Bekaii-Saab, MD: I think it’s important to involve the palliative care doctors. However, I still personally act as a palliative care doctor with my patient until I think I really need that next level.

Transcript Edited for Clarity 

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Transcript: 

Tanios S. Bekaii-Saab, MD: This was the study with FOLFIRINOX into progression. It was limited to 6 months; that’s how the French designed it. Then FOLFIRINOX with maintenance therapy, roughly 4 months, going to 5-FU with reintroduction of the oxaliplatin. There’s a third arm I’m not going to spend much time talking about because I don’t think it has as much relevance in this discussion.

But this study was interesting because it showed essentially that—I think the way I interpreted it, and also what my colleagues think— the maintenance strategy is feasible. That we can go from an induction-intense 3-month FOLFIRINOX, and then deescalate to infusional 5-FU. The one problem with this study was that, although the outcomes were very similar, the toxicities seemed to be higher when you do what I call the stop-and-go of pancreas cancer—FOLFIRINOX, 5-FU and reintroduce oxaliplatin—and it appears that the reintroduction of the oxaliplatin increased the risk of neuropathy. Now, this is not colon cancer where 5-FU can maintain you for 6 months to a year, where the neuropathy of oxaliplatin may be a grade 1. These are patients that get oxaliplatin reintroduced within 3 months, and that may explain essentially the increased risk of neuropathy.

I think, at least the way I interpret this, is FOLFIRINOX followed by 5-FU makes sense, and we should consider it very strongly for most of our patients, if not all. The question that remains is, do we really need to introduce oxaliplatin or should we switch to another regimen at that point?

Eileen M. O’Reilly, MD: Can I give you another take on that? It’s that I would have loved to have seen them ask the question of FOLFIRI as the maintenance.

Kabir Mody, MD: Yes, absolutely.

Eileen M. O’Reilly, MD: Because I think that combination may control the disease for longer and allow you to continue to hold off the oxaliplatin.

Tanios S. Bekaii-Saab, MD: And perhaps reintroduce the oxaliplatin once the stone’s done. Absolutely I agree.

John L. Marshall, MD: I think a lot of this is very important, but it’s a subtlety for us as disease experts. I think that what I’m seeing time and again by our community partners is they just keep going until the patient pops. Whether it’s side effects or fatigue or a treat-to-progression kind of mentality. The theme in GI, at least in colorectal and pancreas, what we’re seeing is that after that induction, it is logical to back off. We are wrestling about what backing off looks like, but that should be a theme. If you’re responding and you’re getting on top of the disease, you need to develop a strategy for backing off.

Eileen M. O’Reilly, MD: I think we have now a reasonable level of evidence to support this and to continue to explore this, because we really need data to help define; but yes, I think so.

George P. Kim, MD: It allows us to take a break. Again, we’re still giving chemotherapy but we’re just not giving them oxaliplatin, so I think it’s useful. But you have to talk to the patient every so often. What does the patient want?

John L. Marshall, MD: Especially if you’re going to bill them.

George P. Kim, MD: Many patients want to keep at it. Some patients have a lot of side effects. They have all the fatigue and the neuropathy, they want to back off, they want to go to Hawaii. Some people don’t want to keep going.

John L. Marshall, MD: But some of that is how we present it at the beginning I think, too. If you go into that first visit with a strategy of saying, “We’re going to get you off the ledge and then see if we can back this off,” I think that patient understands that’s the norm. Versus this culture of the battle of cancer and the war on cancer.

John L. Marshall, MD: We have to keep fighting and there has to be suffering. I always reflect on the long game for those patients—I’m not worried about this Christmas, I’m worried about next Christmas. That gives them a little perspective of what if you say you want to live forever? Well could you keep taking this regimen forever, or do we need to take some breaks?

Tanios S. Bekaii-Saab, MD: Again, it’s the sprint versus marathon analogy that amazingly enough, we’re having these discussions.

John L. Marshall, MD: Yes, it’s a good problem.

Tanios S. Bekaii-Saab, MD: We should be happy that we’re having these discussions and we’re thinking about these issues in pancreas cancer. That means we’re making a much bigger difference.

Kabir Mody, MD: But again, to emphasize the importance of our palliative care colleagues, because they do a very good job of framing that mindset you’re talking about.

Tanios S. Bekaii-Saab, MD: However, I do think that oncologists are great palliative care doctors when they take the time to do it.

Kabir Mody, MD: I agree, yes.

Tanios S. Bekaii-Saab, MD: I think it’s important to involve the palliative care doctors. However, I still personally act as a palliative care doctor with my patient until I think I really need that next level.

Transcript Edited for Clarity 
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