The Evolution of Sequencing Strategies in Pancreatic Cancer - Episode 4

Frontline Decisions in Metastatic Pancreatic Cancer

Transcript:Johanna Bendell, MD: Now you’re saying that we can sequence things differently, we can start at different doses? How do we make that decision? I’m going to give you guys a patient case and see what you would do. So, John, a 65-year-old woman comes in to see you. And she has a performance status of 1—more from anorexia, a little bit of fatigue, that pancreatic cancer patient that’s starting to feel the symptoms. What would you use first-line?

John Marshall, MD: As we’re sitting here talking about this, I know that almost every time, I’m sitting here in this clinic room thinking, “What should I do?” Because they’ll do whatever I say. And if I pitch the 3-drug combo or the 2-drug combo, that’s what they’ll end up doing, right? And so, this really is one of those moments when, yes, you can paint the 2 and let them choose. There will be some toxicities that come out, but in the end, they’ll say, “Well, what do you think I should do?” And I wish I knew. My experience with this is that some people respond to one and not the other, and vice versa. So, you’ll get really good responses with one and not the other.

I tend to be a 2-drug regimen guy. I don’t see the added advantage of what may be a real small increase in response rate, for example, compared to the toxicity. I realize that as an academic oncologist in a big city, I’m supposed to be a 3-drug guy and push these people. But I just don’t. So, there’s that part of me that tips the balance and so often, even in a relatively young, decent PS patient, I’m probably still starting with nab-paclitaxel.

Johanna Bendell, MD: Now 3 weeks on, 1 week off, or every other?

John Marshall, MD: So, I actually do it a little differently. Anyway, I usually go 3 on/1 off. I have a patient right now that yesterday got the text that on week 3 was too low, so I didn’t treat. So, I’ll either go to every other week or 2 on/1 off, depending on where we are. It’s rare, quite honestly, that I can get 3 weeks in a row in most patients.

Johanna Bendell, MD: All right, heterogeneity of opinion. George, what would you do for this patient?

George Kim, MD: I think Abraxane/gemcitabine is very reasonable. I think FOLFIRINOX, modified, is reasonable. So, I would do both. I agree with John, believe it or not, that Abraxane/gemcitabine would be very reasonable for this patient. I don’t know. Would you change this if it was a male patient? I know I’ve asked Eileen this question before.

John Marshall, MD: No.

Johanna Bendell, MD: Now, are you going to every-other-week at MD Anderson, high-dose everything then, or are you going to do a traditional—3 on/1 off?

George Kim, MD: Traditional 3 on/1 off. And if I do run into trouble, I’ll do what John did — 2 weeks on, 1 week off.

Johanna Bendell, MD: Caio?

Caio Max S. Rocha Lima, MD: I’m the same way, and I tend to favor the gemcitabine/nab-paclitaxel because of the sequence. Now we have second-line therapy that is actually FDA-approved and that is based on randomized phase III data. It has been a long journey. We all felt that for prophylactic patients, there was a role for second-line therapy in pancreatic cancer, but that proof of principle is kind of lagging behind, and now we have that. And since 1 of 2 of the components of FOLFIRINOX is part of the second-line treatment in pancreatic cancer, that is also a contributing factor to select another paclitaxel again as first-line. But the main reason is, as Dr. Marshall just mentioned, that this is palliative treatment. We’re not in the curative setting, and giving 3 cytotoxic drugs up front is very challenging.

Johanna Bendell, MD: Eileen?

Eileen O’Reilly, MD: I like both.

Johanna Bendell, MD: You have to pick 1.

Eileen O’Reilly, MD: We’re a little biased because we have a lot of gemcitabine/nab-paclitaxel—based studies. So, we actually use mostly gemcitabine/nab-paclitaxel because it’s a nice building block for adding agents. Outside of the study, it’s probably about 50/50. And like our colleagues here on the panel, a lot of people come having read that one is better than the other or a better fit for them. I really like them both, and I’ve used them both. But I do think the point that Caio made is that we now have the option of sequencing and potentially a third-line. If one starts with gemcitabine/nab-paclitaxel, that may be influencing the decision a bit in terms of encouraging more people in that direction and how we can strategize to get the most mileage from all the tools available over time.

John Marshall, MD: When I started in on this, I really thought it was the oxaliplatin, and the irinotecan was along for the ride. I don’t know if you guys think the same way, but now that we have second-line negative studies with FOLFOX, I’m wondering if it’s really the irinotecan. In the 3-drug cocktail, is there magic among the 3 drugs or is it really just fluoropyrimidine or irinotecan that’s carrying the day? And so, some of that influences my decisions. I’m less excited about oxaliplatin in this drug than I used to be. I think that has changed some in my practice.

Johanna Bendell, MD: So, is there anybody in the first-line metastatic setting that you could think of? Is there any patient profile you could think of where you would use FOLFIRINOX first-line?

Caio Max S. Rocha Lima, MD: BRCA2. I’m sorry.

Eileen O’Reilly, MD: I was going to say that. So, that’s exactly right. If one is thinking that the patient has either a known BRCA mutation or a high probability, I think having the DNA-damaging agents with oxaliplatin and with irinotecan is potentially attractive, and I would sway.

George Kim, MD: Alright, so which one is it? Is it the oxaliplatin or the irinotecan that’s best for BRCA?

Caio Max S. Rocha Lima, MD: I think both.

Eileen O’Reilly, MD: I think neither of them are the best. I think cisplatin is probably the best drug, but the combination is good.

John Marshall, MD: So, then they’re both being tested with parts, too, so that seems to be active.

Eileen O’Reilly, MD: Yes.

George Kim, MD: I want to bring up something John just said: IROX. Remember that regimen? There was an interaction between irinotecan and oxaliplatin. I think we forget about the interactions. We forget that oxaliplatin almost died when it was used in monotherapy. And it was only when the French combined it with 5-FU that they really showed that it worked. And then Rich Goldberg brought it to United States soil and he finally showed that it worked in colorectal cancer. So, there’s an interaction between all 3 drugs.

John Marshall, MD: There’s a young patient, I’d say under 60 years old, with a lot of tumor burden who really needs a response. I’d probably give them a couple cycles of FOLFIRINOX and see what I can get out of that. I would bring that bias to the table. Even if there is some truth to the higher response rate, I want every angle I can get in that patient where I need a response.

Johanna Bendell, MD: Right, up front.

Transcript Edited for Clarity