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Practical Advice: Pancreas Cancer Adjuvant Therapy

Panelists: Edward Kim, MD, University of California Davis; John Marshall, MD, Georgetown University Lombardi Comprehensive Cancer Center; Paul Oberstein, MD, NYU Langone Perlmutter Cancer Center; Allyson Ocean, MD, Weill Cornell Medical College; Shubham Pant, MD, The University of Texas MD Anderson Cancer Center
Published: Saturday, Aug 17, 2019



Transcript:

John Marshall, MD: Paul, for me, this study is kind of practice changing for many of us, because when I was giving neoadjuvant for locally advanced or borderline tumors, I thought I had a choice. I thought I had a choice between nab-paclitaxel, GEM [gemcitabine], and FOLFIRINOX [folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin]. Depending on the performance status of the patient, there are some patients you just can’t give FOLFIRINOX to. What do you think this negative adjuvant data does to those folks who are thinking about neoadjuvant GEM/nab-paclitaxel?

Paul Oberstein, MD: I don’t think the data answer that clearly, because that was not the question in the study. The same way that there is still some ambiguity in the neoadjuvant setting, and certainly some patients who benefit from GEM/nab-paclitaxel—it’s more tolerable, maybe—and get some really good responses, there may be some similar people in the neoadjuvant setting. Some of it depends on whether your neoadjuvant patient is really a surgical patient in whom you’re preloading the chemotherapy, in which case, FOLFIRINOX is the clear winner in my opinion.

John Marshall, MD: If you’re really giving the adjuvant part.

Paul Oberstein, MD: If you’re really giving the adjuvant part, or if they’re so locally advanced that you don’t think they’re going to get to surgery, in which case you may be treating them as a metastatic patient. There are some settings where it would make sense to give GEM/nab-paclitaxel.

John Marshall, MD: Yes. Anybody disagree with that?

Shubham Pant, MD: No. Actually, I think it’s a really good point.

John Marshall, MD: Any other new data around neoadjuvant that have come out at this meeting, in terms of shifting practice patterns? Anybody?

Shubham Pant, MD: I think the big one was in ASCO GI [American Society of Clinical Oncology Gastrointestinal Cancers Symposium], as I said, which was the Japanese study that came out for resected cancer patients with the neoadjuvant. We’ve got other trials that are going on through the different cooperative group networks about gemcitabine-abraxane versus FOLFIRINOX that we are seeing. Really, if you look at the data, I do think that FOLFIRINOX is a fairly solid regimen for patients who can tolerate it, at least in the adjuvant setting. The survival curves were amazing in FOLFIRINOX. Again, they had good patient selection, but they still had a median overall survival of 54.4 months. When you looked at those curves last year at ASCO [American Society of Clinical Oncology Annual Meeting], that was amazing to see in patients with pancreatic cancer.

Allyson Ocean, MD: That didn’t make the plenary.

John Marshall, MD: That didn’t make the plenary.

Shubham Pant, MD: I think all of us were fairly disappointed about that, because it was truly practice changing. The other thing I want to discuss for our audience is, when you look at the original trial for FOLFIRINOX, they gave bolus 5-FU [5-fluorouracil] and irinotecan at 180 mg/m2, but when you look at the adjuvant study, there was no bolus 5-FU. In the clinical setting, I don’t think anybody really gives bolus 5-FU, and then the irinotecan was decreased to 150 mg/m2.

John Marshall, MD: After a while.

Shubham Pant, MD: After a while, because of tolerability. I really think when you look at FOLFIRINOX, a lot of the data we have regarding tolerability is at these higher doses, so when you adjust the dose of FOLFIRINOX, I think it is more tolerable in patients.

John Marshall, MD: Anybody do something different from that in terms of your modification? Drop the bolus? Reduce your irinotecan? Anybody fiddle with it more?

Paul Oberstein, MD: Give a lot of growth factors.

John Marshall, MD: You give growth factors. That’s the only time I ever give a growth factor.

Paul Oberstein, MD: I give a lot of hydration.

Allyson Ocean, MD: You keep the regular dose and give growth factors?

Paul Oberstein, MD: No, I do this and give them, usually every other cycle. We almost always start with cycle 1, unless they already have a good count, and then do cycle 3, depending on what they need.

John Marshall, MD: It’s much more involved. That raises the cost of the regimens.

Paul Oberstein, MD: We also like them to come back. We often have them come back week 2 to just get hydration and check in.

Allyson Ocean, MD: Yes.

Edward Kim, MD: That’s what we do.

John Marshall, MD: How much is parking at your place?

Shubham Pant, MD: I normally don’t give growth factors.

John Marshall, MD: In my place, it’s a big deal.

Shubham Pant, MD: We don’t normally give growth factors, but I do think a good anti-nausea regimen is very important in these patients, because if you’re not getting anything for the delayed nausea, then you can really get into trouble. Hydration is very important. It’s amazing how a bag of hydration can make these patients feel.

John Marshall, MD: How many cycles?

Paul Oberstein, MD: In the adjuvant setting?

John Marshall, MD: Adjuvant.

Shubham Pant, MD: I mean, 12 cycles is the—

John Marshall, MD: Who does that?

Allyson Ocean, MD: We try.

John Marshall, MD: You try.

Shubham Pant, MD: We try to get there, yes.

Edward Kim, MD: Even in the trial, they couldn’t do that.

Paul Oberstein, MD: We try.

John Marshall, MD: I don’t even try. I have to tell you.

Paul Oberstein, MD: We treat it like advanced localized colon cancer, and we aim for 12. We drop the OXALI [oxaliplatin], like everyone, 6 to 8 cycles in.

John Marshall, MD: I shoot for only 6; I have to tell you right now. I think we’re done.

Paul Oberstein, MD: Then do you continue the…

John Marshall, MD: I do some funky stuff beyond that.

Shubham Pant, MD: Obviously, you get into toxicity and everything, but the standard was 12.  A lot of people couldn’t get to it. Another thing with FOLFIRINOX is that we look at retrospective data and patients more than 75 years of age. If you remember, the original metastatic setting did not include these patients who were more than 75. We looked at our retrospective data presented at ASCO GI in January of this year, and those patients in which you dose adjusted—and our oldest 1 was 83 years old, who got FOLFIRINOX—they actually did fairly well. The irinotecan dosing was mostly 120 mg/m2. That seems to be fairly tolerable when you decrease it. A lot of people got reduced to 65 mg/m2 of oxaliplatin, but our survival in frontline for this metastatic—again, it’s retrospective, small numbers—was about 11 months, which is very similar to what it was.

John Marshall, MD: We still have miles to go, yes.

Edward Kim, MD: I think there still needs to be a point for the community oncologists in terms of FOLFIRINOX. We do all these adjustments to support the patients, because it is a difficult regimen. At the end of the day, I think we can’t lose sight of that. You do need to select patients carefully. It’s after a Whipple or another major surgery like a distal pancreatectomy. It’s going to be a major surgery. It’s going to be difficult, and even with these modifications and all the supportive care that we do, it’s not easy therapy. I think we are blown away with the 55-month survival.

John Marshall, MD: Again, that’s selection too. If you can fly and make it through George Bush Intercontinental Airport in Houston, Texas, and get to your hospital, The University of Texas MD Anderson Cancer Center, that means you’re 55 years old; you’re not 78.

Shubham Pant, MD: I completely agree. It’s patient selection.

Transcript Edited for Clarity

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Transcript:

John Marshall, MD: Paul, for me, this study is kind of practice changing for many of us, because when I was giving neoadjuvant for locally advanced or borderline tumors, I thought I had a choice. I thought I had a choice between nab-paclitaxel, GEM [gemcitabine], and FOLFIRINOX [folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin]. Depending on the performance status of the patient, there are some patients you just can’t give FOLFIRINOX to. What do you think this negative adjuvant data does to those folks who are thinking about neoadjuvant GEM/nab-paclitaxel?

Paul Oberstein, MD: I don’t think the data answer that clearly, because that was not the question in the study. The same way that there is still some ambiguity in the neoadjuvant setting, and certainly some patients who benefit from GEM/nab-paclitaxel—it’s more tolerable, maybe—and get some really good responses, there may be some similar people in the neoadjuvant setting. Some of it depends on whether your neoadjuvant patient is really a surgical patient in whom you’re preloading the chemotherapy, in which case, FOLFIRINOX is the clear winner in my opinion.

John Marshall, MD: If you’re really giving the adjuvant part.

Paul Oberstein, MD: If you’re really giving the adjuvant part, or if they’re so locally advanced that you don’t think they’re going to get to surgery, in which case you may be treating them as a metastatic patient. There are some settings where it would make sense to give GEM/nab-paclitaxel.

John Marshall, MD: Yes. Anybody disagree with that?

Shubham Pant, MD: No. Actually, I think it’s a really good point.

John Marshall, MD: Any other new data around neoadjuvant that have come out at this meeting, in terms of shifting practice patterns? Anybody?

Shubham Pant, MD: I think the big one was in ASCO GI [American Society of Clinical Oncology Gastrointestinal Cancers Symposium], as I said, which was the Japanese study that came out for resected cancer patients with the neoadjuvant. We’ve got other trials that are going on through the different cooperative group networks about gemcitabine-abraxane versus FOLFIRINOX that we are seeing. Really, if you look at the data, I do think that FOLFIRINOX is a fairly solid regimen for patients who can tolerate it, at least in the adjuvant setting. The survival curves were amazing in FOLFIRINOX. Again, they had good patient selection, but they still had a median overall survival of 54.4 months. When you looked at those curves last year at ASCO [American Society of Clinical Oncology Annual Meeting], that was amazing to see in patients with pancreatic cancer.

Allyson Ocean, MD: That didn’t make the plenary.

John Marshall, MD: That didn’t make the plenary.

Shubham Pant, MD: I think all of us were fairly disappointed about that, because it was truly practice changing. The other thing I want to discuss for our audience is, when you look at the original trial for FOLFIRINOX, they gave bolus 5-FU [5-fluorouracil] and irinotecan at 180 mg/m2, but when you look at the adjuvant study, there was no bolus 5-FU. In the clinical setting, I don’t think anybody really gives bolus 5-FU, and then the irinotecan was decreased to 150 mg/m2.

John Marshall, MD: After a while.

Shubham Pant, MD: After a while, because of tolerability. I really think when you look at FOLFIRINOX, a lot of the data we have regarding tolerability is at these higher doses, so when you adjust the dose of FOLFIRINOX, I think it is more tolerable in patients.

John Marshall, MD: Anybody do something different from that in terms of your modification? Drop the bolus? Reduce your irinotecan? Anybody fiddle with it more?

Paul Oberstein, MD: Give a lot of growth factors.

John Marshall, MD: You give growth factors. That’s the only time I ever give a growth factor.

Paul Oberstein, MD: I give a lot of hydration.

Allyson Ocean, MD: You keep the regular dose and give growth factors?

Paul Oberstein, MD: No, I do this and give them, usually every other cycle. We almost always start with cycle 1, unless they already have a good count, and then do cycle 3, depending on what they need.

John Marshall, MD: It’s much more involved. That raises the cost of the regimens.

Paul Oberstein, MD: We also like them to come back. We often have them come back week 2 to just get hydration and check in.

Allyson Ocean, MD: Yes.

Edward Kim, MD: That’s what we do.

John Marshall, MD: How much is parking at your place?

Shubham Pant, MD: I normally don’t give growth factors.

John Marshall, MD: In my place, it’s a big deal.

Shubham Pant, MD: We don’t normally give growth factors, but I do think a good anti-nausea regimen is very important in these patients, because if you’re not getting anything for the delayed nausea, then you can really get into trouble. Hydration is very important. It’s amazing how a bag of hydration can make these patients feel.

John Marshall, MD: How many cycles?

Paul Oberstein, MD: In the adjuvant setting?

John Marshall, MD: Adjuvant.

Shubham Pant, MD: I mean, 12 cycles is the—

John Marshall, MD: Who does that?

Allyson Ocean, MD: We try.

John Marshall, MD: You try.

Shubham Pant, MD: We try to get there, yes.

Edward Kim, MD: Even in the trial, they couldn’t do that.

Paul Oberstein, MD: We try.

John Marshall, MD: I don’t even try. I have to tell you.

Paul Oberstein, MD: We treat it like advanced localized colon cancer, and we aim for 12. We drop the OXALI [oxaliplatin], like everyone, 6 to 8 cycles in.

John Marshall, MD: I shoot for only 6; I have to tell you right now. I think we’re done.

Paul Oberstein, MD: Then do you continue the…

John Marshall, MD: I do some funky stuff beyond that.

Shubham Pant, MD: Obviously, you get into toxicity and everything, but the standard was 12.  A lot of people couldn’t get to it. Another thing with FOLFIRINOX is that we look at retrospective data and patients more than 75 years of age. If you remember, the original metastatic setting did not include these patients who were more than 75. We looked at our retrospective data presented at ASCO GI in January of this year, and those patients in which you dose adjusted—and our oldest 1 was 83 years old, who got FOLFIRINOX—they actually did fairly well. The irinotecan dosing was mostly 120 mg/m2. That seems to be fairly tolerable when you decrease it. A lot of people got reduced to 65 mg/m2 of oxaliplatin, but our survival in frontline for this metastatic—again, it’s retrospective, small numbers—was about 11 months, which is very similar to what it was.

John Marshall, MD: We still have miles to go, yes.

Edward Kim, MD: I think there still needs to be a point for the community oncologists in terms of FOLFIRINOX. We do all these adjustments to support the patients, because it is a difficult regimen. At the end of the day, I think we can’t lose sight of that. You do need to select patients carefully. It’s after a Whipple or another major surgery like a distal pancreatectomy. It’s going to be a major surgery. It’s going to be difficult, and even with these modifications and all the supportive care that we do, it’s not easy therapy. I think we are blown away with the 55-month survival.

John Marshall, MD: Again, that’s selection too. If you can fly and make it through George Bush Intercontinental Airport in Houston, Texas, and get to your hospital, The University of Texas MD Anderson Cancer Center, that means you’re 55 years old; you’re not 78.

Shubham Pant, MD: I completely agree. It’s patient selection.

Transcript Edited for Clarity
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