John Marshall, MD: Let’s shift gears a little bit now and go into the metastatic setting. I’m going to ask Ed to give me a start-off on how you assess a patient. Somebody comes in and presents with metastatic disease. How do you decide what to do with that patient in the absence of a clinical trial?

Edward Kim, MD: In the absence of a clinical trial, there are, in my opinion, 2 standards of care: FOLFIRINOX [folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin] and GEM [gemcitabine]/nab-paclitaxel. We do not have, at this point, head-to-head data to compare the 2. This is different from the adjuvant setting we’ve been talking about, where you have nothing to follow. In this setting we at least have something to follow. For me, fundamentally, it comes down to patients’ fitness but also their goals of care. We have to recognize the really difficult position these patients are in with metastatic disease, oftentimes with not-great performance status, needing something for not just treatment but palliation. We can’t lose sight of that aspect of it. It’s very important what my patients’ goals of care are.

John Marshall, MD: In colon cancer, we’re seeing this shift back, from just making sure everybody gets all the treatment to an induction concept, where it’s justified to give more intensive care therapy up front and then maybe back off to a maintenance kind of approach. Paul, do you see that happening here as we think about frontline regimens?

Paul Oberstein, MD: I do, but I think there’s a challenge in pancreatic cancer that is not as common in colon cancer, which is that often patients, even young, previously healthy patients, come in very symptomatic. They’ve lost a lot of weight, they’re in pain, and they’re miserable. It’s difficult to go in on day 1 and blast them with everything we have. There are times where that’s not the case, but sometimes we have to escalate the chemotherapy. We have to ease them into it, but I do think that we see that in that first 2 to 4 months of chemo; we want to give as much as we can.

John Marshall, MD: It’s sort of like you can’t afford to be wrong in a lot of these patients. It’s the exception that you can get to progression of disease at 2 months or 4 months and switch. Are you thinking lines of therapy right from the beginning, or are you thinking, “Let’s just get off the ledge first and see where we are?” Allyson?

Allyson Ocean, MD: I’m thinking of lines of therapy. I also try to work with our precision medicine program to make organoids and do drug testing, so that we can try to sprinkle this on and sprinkle that on, which is going to work the best. It really works only when you need it right then, because as you treat them, the tumors change and mutate. I try to think about what I’m going to do next early on, and I do push through even though they’re so symptomatic. It’s the disease, and as soon as they respond, they feel so much better.

John Marshall, MD: So much better. You know it’s happening.

Allyson Ocean, MD: I pray that I’m going to be able to get them through it, and I’m like, “What am I doing?” I’m giving them a really hard regimen, but I just try to get them through it the best I can so that they have a chance of responding.

John Marshall, MD: Yes. I hate this decision, because I don’t really know what to do. At least in my clinical experience, it seems as if some patients will respond to 5-FU [5-fluorouracil]-based therapy and some will respond to GEM-based therapy, and it’s very hard to predict. Also, tolerance—some will find 1 very easy and the other difficult, and vice versa. Are we ever going to get a biomarker that will help me say, “I’m going to give this patient FU-based therapy or this one GEM-based therapy?”

Shubham Pant, MD: I think people have tried. Again, it’s unclear which 1. I think the best biomarker we could use right now is the germline testing for BRCA, and if they’re BRCA-positive, use platinum.

John Marshall, MD: It steers you toward platinum-based therapy.

Shubham Pant, MD: It steers me toward platinum, so I think that’s the best kind of biomarker we have versus anything else we’ve tried till now.

Transcript Edited for Clarity