John Marshall, MD: This is always a provocative question, but I’m old enough to remember when 5-FU [5-fluorouracil] tied GEM [gemcitabine], and then GEM became the standard, and everything was tied to GEM. Then 5-FU comes back, and this kitchen-sink approach of FOLFIRINOX [folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin] against GEM single-agent becomes this new regimen. When you start to take the pieces apart, and you look at oxaliplatin by itself or irinotecan by itself, you see variable activity. The unfair question of all this is, do you think this is really secret sauce and that there’s some synergy among these 3 drugs? Or do you think it’s legitimate to deconstruct, let’s say, in the absence of a BRCA? It’s an unfair question. Do you want it? Do you want it, Paul?

Paul Oberstein, MD: I think in colon cancer, the data exists that all 3 are better than 2.

John Marshall, MD: Three are better. We do see response rate…

Paul Oberstein, MD: Response rate.

John Marshall, MD: Versus sequential. We have that data.

Paul Oberstein, MD: I think it’s true in pancreatic cancer. The more complicated question, which you’re getting to: is it enough to do 2? Can you do FOLFIRI [leucovorin calcium, 5-fluorouracil, irinotecan] or liposomal irinotecan plus 5-FU and get another line in there? Would the patients do better over time? The only way to know that is through clinical trials.

John Marshall, MD: Yes, and I think maybe this BRCA window might help us with that. Maybe we do think about sorting out the platinum-based therapies there, and then these other nonenriched populations.

Shubham Pant, MD: Yeah, I think we’ve learned a lot from the colorectal data. PRODIGE35 from last year really spelled it out, which was FOLFIRINOX for 4 months followed by 5-FU, exactly as we would do from the OPTIMOX trials from colorectal, versus FOLFIRINOX until progression. If you go on 5-FU and reintroduce FOLFIRINOX, those patients actually had a comparable disease-free survival and overall survival. In patients who can tolerate it, I would start with FOLFIRINOX, do the 4 months, and then try to do a maintenance approach.

John Marshall, MD: I think this is great. This is what I like to do. Has anybody got a favorite recipe for maintenance? What does that look like? Let’s say it’s great, they’ve had 8 cycles, they’re not dead yet, and they’re OK. You say, “Let’s back off for a little bit.” What does that look like?

Paul Oberstein, MD: It depends.

John Marshall, MD: What’s your favorite?

Paul Oberstein, MD: If they have nausea and diarrhea, it looks like 5-FU alone.

John Marshall, MD: So just pump?

Paul Oberstein, MD: Pump, or even the pill or capecitabine.

John Marshall, MD: Capecitabine—some sort of 5-FU—based therapy.

Paul Oberstein, MD: If they can handle it, I like to continue FOLFIRINOX.

John Marshall, MD: Keep the irinotecan going.

Edward Kim, MD: That’s my approach.

John Marshall, MD: Keep the irinotecan going.

Allyson Ocean, MD: I agree—FOLFIRINOX.

Shubham Pant, MD: You’ll burn out with the neuropathy sooner or later with the patients. I do think you can choose either FOLFIRI or 5-FU maintenance. To keep FOLFIRINOX or FOLFOX [folinic acid, 5-fluorouracil, oxaliplatin] going for some time is fairly challenging in these patients, so I tend to more go toward—depending on the disease control, obviously—either FOLFIRI—based or 5-FU–based therapy. Data on 5-FU–based therapy does say that the survival is very equal to FOLFIRINOX.

Paul Oberstein, MD: Can I throw in a hard question? Do we have time? I have patients—and it’s not an insignificant number—who are doing great on FOLFIRINOX. You drop the OXALI [oxaliplatin], and they fall apart. Their markers rise. What do you do then?

John Marshall, MD: Rechallenge, right?

Paul Oberstein, MD: I never find that rechallenging is that successful. You can go to gemcitabine-based therapy, but…

John Marshall, MD: That’s the fear of backing off; you lose those patients.

Paul Oberstein, MD: I think it’s clear that some maybe didn’t even need OXALI to begin with. They get the FOLFIRI, and they’re swimming for a year.

John Marshall, MD: It’s a bad disease, right? It’s not like you’ve got multiple windows downstream to deal with this.

Edward Kim, MD: The difficult question for me is, we’re talking about maintenance versus keeping more intensive therapy and evidence for minimal—say, just 5-FU alone—versus a break entirely.

John Marshall, MD: Just a total break.

Edward Kim, MD: Do we—

John Marshall, MD: We’re going to talk about 1 in just a minute. We’re going to talk about a study that did that, and I think it’s very informative. It certainly hasn’t been the tradition with this disease. Even in colon cancer, there’s a subset that I think about doing that with. Are you doing that sometimes?

Edward Kim, MD: I am sometimes forced.

John Marshall, MD: Is it a break to go to Disney World, or is it a break until you progress on your scan?

Edward Kim, MD: I don’t think a break to go to Disneyland is a break. That’s life.

John Marshall, MD: Disneyland.

Edward Kim, MD: Or Disney World.

John Marshall, MD: Yours is the cooler one, really.

Edward Kim, MD: I think it is an important question. There is some value, especially for these patients. This is a dismal prognosis, and even minimal chemotherapy is still either being tied to a pump or the toxicity of capecitabine, so I don’t think it’s a trivial question.

John Marshall, MD: No, that’s a great question.

Transcript Edited for Clarity