Sequencing Decisions in Advanced Pancreatic Cancer

Transcript:Johanna Bendell, MD: So, Caio and Eileen said that having this drug (nanoliposomal irinotecan) present in the armamentarium for treatment may influence the first-line treatment decision to maybe going more toward gemcitabine/nab-paclitaxel. Then you would have 5-FU (fluorouracil) and liposomal irinotecan second-line. Does that influence you?

George Kim, MD: It definitely influences me, because you know that with Abraxane and gemcitabine you can get thrombocytopenia and neuropathy. Those are not side effects that you see with the nanoliposomal irinotecan regimen. So, you rest the bone marrow and you rest the nerves. And it makes a lot of sense to go from one FDA-approved drug to another FDA-approved drug. So that sequence, I think, is becoming more and more accepted and used.

I agree with John. I’d like to think that these drugs deposit in the tumor, the stroma, and the desmoplasia and get to the cancer cells over a prolonged period. We know the pharmacology is very different with this nanoliposomal irinotecan regimen, so I want to believe that it is doing that and that we’re getting to the tumor. The sequencing is going to be important.

Now, if this PEGPH20 compound is a positive study—this phase III trial—then we’re all going to be using nab-paclitaxel and gemcitabine up front with this third agent. Then, we will be going down to nanoliposomal irinotecan in the second-line setting. We may be heading in that direction anyway.

John Marshall, MD: Yes. I’m thinking about the whole chessboard when I start the game. And so, what have I got to play and when am I going to play it? So, certainly having these kinds of options through second-line makes me feel a little better about first-line choices.

Johanna Bendell, MD: Okay, so I’m going to throw this out there. You’ve got gemcitabine/nab-paclitaxel. You’ve got 5-FU/ nanoliposomal irinotecan. Do you use FOLFOX (folinic acid/5-FU/oxaliplatin) third-line?

Eileen O’Reilly, MD: Absolutely. I think oxaliplatin has demonstrated activity in this disease, and if the person is strong enough and well enough for it, and their neuropathy isn’t too uncomfortable, I think FOLFOX is at least a rational consideration—although not clearly supported by data in this setting. And as John alluded to, we have mixed data for the value of oxaliplatin, second-line, with 1 positive study and 1 negative study. So, take your pick in terms of where you fall. But nonetheless, it does have activity. That’s already known from FOLFIRINOX, so it’s rational. In the absence of a suitable trial per line, I think FOLFOX is the “go-to” regimen in that setting versus infusional 5-FU—but that’s less attractive.

Johanna Bendell, MD: So, it sounds like, and please correct me if I’m wrong, outside of specific patient populations (the BRCA patient, or the patients with a large disease burden that need a really immediate response), in general on this panel, we’re looking at gem/nab followed by 5-FU/nanoliposomal irinotecan, followed possibly by FOLFOX? Is that about right?

John Marshall, MD: Who would have thought we’d be talking about 3 lines of therapy in pancreatic cancer and the change in the paradigm for this. It’s really exciting. But I will throw out a note: we all work at places where we’re getting patients to third-line. We have a research network, which incorporates a lot of other community-based hospitals and the like. And we keep saying, “Don’t you want to open this third-line pancreas study?” And they’re like, “We don’t have third-line pancreas cancer.” It’s a different patient. So, I do think the decisions around first- and second-line are even more important for the patient who comes in starting with a 1.5 performance status with a little less social support than the ones that are making it to our centers. It’s cool that we’re thinking about it, but I also, every day, face the other side where they don’t have third-line patients.

Johanna Bendell, MD: Well, let’s say you’ve got somebody that comes to you with a performance status of 2 right off the bat and not a lot of social support. Is there a role or would you ever use gemcitabine monotherapy again?

John Marshall, MD: Almost never anymore. First off, the doublet’s easy, right? It’s not that hard on patients. You’ve got all these dosing schemes that people have, and so you can get this in. And particularly if their performance status is down because of disease, it’s backwards thinking to give gemcitabine monotherapy, in my opinion. I can’t think of the last time I gave gemcitabine monotherapy since nab-paclitaxel came on the market.

Johanna Bendell, MD: Anybody?

George Kim, MD: The MPACT trial shows that there’s a month benefit in performance status, too. So, yes, there is a benefit there. So, it makes a lot of sense to continue with the doublet instead of going back to just gemcitabine monotherapy. Please don’t use erlotinib monotherapy. We do see that used from time to time. Please don’t do that. If you’re going to use Xeloda (capecitabine), be careful with your proton pump inhibitors.

Transcript Edited for Clarity