Deciding Among Frontline Standards of Care in Pancreatic Cancer

Transcript:Johanna Bendell, MD: We have these two chemotherapy regimens that you mentioned, gemcitabine/nab-paclitaxel and FOLFIRINOX. There are a lot of people who feel strongly towards one regimen versus another, and certainly it’s the subject of a lot of debate. And maybe to level set, Tom, can you tell us a little bit about the two trials that approved these regimens? What were the patient populations like and what did the data really show us?

Thomas A. Abrams MD: The FOLFIRINOX trial, or the PRODIGE 4 trial, differed from the MPACT trial in patient selection. Patients in the FOLFIRINOX trial really all came from France. They had, for the most part, a better performance status than the folks in the MPACT trial. They were ECOG 0 and 1, whereas the folks in MPACT were KPS 70% and above, which really doesn’t necessarily translate evenly, but may in fact show that there were a little bit poorer performance status patients getting the gemcitabine and the nab-paclitaxel. But, on the other hand, both control arms were gemcitabine, and the overall survivals were essentially identical.

So, it does make one question whether they were really truly meaningful differences in the trials with respect to the patients. That said, clearly, the FOLFIRINOX patients had more in the way of toxicity, slightly more in the way of neutropenia and diarrhea than those in the MPACT trial randomized to the experimental arm. And they had a much higher overall survival, 11 months versus 8.5 months. So, I think based on those data, most people feel that FOLFIRINOX might be a little bit more effective, might have a better response rate, but it’s again with the proviso that cross-trial comparison is very, very difficult and fraught with landmines.

Johanna Bendell, MD: So certainly, outside of a clinical trial, I just want to take a poll because I want to see if I’ve got some controversy here. Which would you like? What do you think, FOLFIRINOX or gemcitabine/nab-paclitaxel?

George P. Kim, MD: It depends on the patient. What does the patient want to do? Does the patient want to wear a pump and have potential toxicities, be hospitalized, need Neupogen, Neulasta? Or do they want to get treated weekly, maybe come in every week and go home, stay at work and still be able to support their family and get their insurance? I think it depends on what the patient wants and what best fits them. I’m going to stir the pot a little bit. There are good survival data. There’s this kind of urban legend that we’re supposed to use FOLFIRINOX in the really good performance status patients, but there are data out there in the KPS ECOG 0 patient that survival can be as high as 12.6 months, and that data is out there in the public domain.

Philip A. Philip, MD, PhD, FRCP: With FOLFIRINOX?

George P. Kim, MD: No, with gemcitabine/Abraxane. So it’s somewhat of a myth. You can use gemcitabine/Abraxane, especially out in the community, I think there is some fear that if you don’t have the support for FOLFIRINOX, you run into side effects. Gemcitabine or Abraxane is a very reasonable option in that population, that good performance status population. I think the other end of it is, the poor performance status patients we always think, well, let’s just give them gemcitabine. But you can give them gemcitabine and Abraxane, and there does appear to be a benefit to that group of patients as well.

Johanna Bendell, MD: Okay, so great political answer. A patient is 60 years-old, good performance status. Straight off the bat, you have to pick something off the shelf, what do you pick?

George P. Kim, MD: Clinical trial.

Johanna Bendell, MD: No clinical trial available. Your research nurse has gone on vacation to Florida.

George P. Kim, MD: Again, it’s a conversation with the patient. What does the patient want? I make very few decisions. I really partner with the patient, try to figure out what they want to do. And I think both are reasonable in that population, at that age, and that performance status. So, I think it’s very reasonable. But, again, ideally, as Philip said earlier, an experimental trial. We’ve got a lot of work to do. We do have new options. We’ve got a lot of work to do, folks. We’re still not hitting the mark.

Johanna Bendell, MD: Tom?

Thomas A. Abrams MD: I think for the young 60 year-old that you described, if we do not have a clinical trial for them, I tend to put patients on FOLFIRINOX, but I don’t think that there is one answer. I think that some patients respond really well to FOLFIRINOX, and others don’t. Whatever you choose may not be the right answer, and sometimes you’ll go that next line, and you’ll find that the patients are doing much better. So it’s a bit of a crap shoot, and I think I still tend to go to FOLFIRINOX in those patients, but I don’t have a definite preference.

Johanna Bendell, MD: Caio?

Caio Rocha Lima, MD: Very well said by the group. But I think, Johanna, we are moving to a new paradigm now. We’re thinking about sequence. We actually have the option in pancreatic cancer, believe it or not, so it’s going to be a discussion further along among us. But now we have irinotecan in a new formulation that showed a benefit in survival combined to 5-FU in second-line gemcitabine-pretreated patients.

So it threw us off a little bit in how to choose the first line because if you pick FOLFIRINOX, you don’t have randomized phase III data with gemcitabine/nab-paclitaxel in second-line. But you now have randomized phase III data with 5-FU and the Merrimack nanoparticle irinotecan compound. I tend to go for sequence, because I think I would also diminish the risk for toxicities for the patient, and I’ll be basing phase III trial in my first-line and second-line treatment.

Johanna Bendell, MD: I love it. Okay. And we are going to talk about the new compound, the MM-398. Philip, last word.

Philip A. Philip, MD, PhD, FRCP: I have to admit that if a patient comes to me who’s young, let’s say 60 years or younger and very good performance status, good organ function, I have that tendency to recommend FOLFIRINOX over gemcitabine/nab-paclitaxel. Although, I always discuss with them. But if I want to think back, the concept of a triplet versus a doublet, and, again, I really appreciate what you said, I think that’s a very important point. If we can sequence more tolerable treatments, easier treatments for patients to take…if you look back into other tumor types, we use triplets in gastric patients.

Now we’re using a doublet most of the time. The same thing would be true in colon cancer. How often do you use FOLFOX here as opposed to the doublets? So, the precedent is there that we use the more tolerable, easier doublets and try to maintain the patient as long as possible on chemotherapy rather than give them therapy that may be more toxic.

Transcript Edited for Clarity