John L. Marshall, MD: Progress in the adjuvant space and neoadjuvant space, and I would say enough to be practice changing in the weeks ahead. The number I use in my head is that somewhere around 10%, not more than 20%, of patients are even candidates for surgery in neoadjuvant. Unfortunately, most are metastatic. Is that same number in all of your head? Has that shifted any much?

Eileen M. O’Reilly, MD: I think it’s increasing just because of this strategy of the locally advanced group.

John L. Marshall, MD: We’re picking up more.

Eileen M. O’Reilly, MD: Yes. It’s probably about a fifth of all patients, plus or minus.

John L. Marshall, MD: Fair enough. Unlike the other cancers, where adjuvant is king and metastatic is the minority, we’re the other way around. George, I’ll let you take the lead on this in setting the stage on metastatic disease. Where are we with the base regimens today that we walk into ASCO with and the management of that disease from a big picture?

George P. Kim, MD: We have 2 regimens that we can choose in the frontline: FOLFIRINOX, obviously, and gemcitabine/nab-paclitaxel. Much like what has happened in the metastatic setting, I think what we’re going to see in the adjuvant setting is a lot of patient selection; what patients should go on which treatment. FOLFIRINOX certainly has its survival over 11.1 months. People feel that it has good efficacy. It comes with side effects, though; lots of neutropenia; a need for growth factor; some neuropathy, as you would expect; and with some diarrhea. Gemcitabine/nab-paclitaxel given weekly was relatively well tolerated, especially out in the community. This was a trial that was done globally, so it applies to the everyday patient. And that’s where we have to make our decision point, so how do you do that?

John L. Marshall, MD: Do you see that there are big differences between those 2 recipes in terms of outcome?

George P. Kim, MD: It depends. The trials were done. They’re very different, especially in regard to patient selection.

John L. Marshall, MD: But in your hands—when you think about it and are making a decision, and the patient is in front of you.

George P. Kim, MD: I think they’re very similar. Again, the toxicities are manageable.

John L. Marshall, MD: Would anybody counter that? I mean, I really hate this question in clinic. You’re describing these 2 regimens to patients and 1 sort of feels easy, and the other 1 feels hard. I know that our staff, to manage FOLFIRINOX, all have to get involved. There’s a lot of management. It’s going to be harder on that patient, and I’m thinking, “Well, what will I do to me in this setting?” I realize there may be some advantage to the 3-drug regimen over the 2-drug regimen. Does anybody push me back to say, “No, I think we really should use the 3-drug in most people” or “No, we should think 2-drug”? Kabir, what do you think? You’re struggling with it, too. I can see it in your faces.

Kabir Mody, MD: In the metastatic setting, the mind-set is different than in the adjuvant setting obviously, right? We’re trying to treat that patient’s disease and also provide them with the best quality of life possible, and every patient’s different.

John L. Marshall, MD: Is this back to colon cancer, where you just get all the drugs in if we can and whatever recipe works?

Eileen M. O’Reilly, MD: I think that rings true for this disease, and there are some data now. It came up in our neoadjuvant setting, but looking at giving FOLFIRINOX and then switching, giving gemcitabine/nab-paclitaxel…we’re seeing selectively in good performance status patients, survivals from European and US studies of 18-plus months. I think it’s real.

Tanios S. Bekaii-Saab, MD: I agree. Let’s take a step back, this is what I’m saying. First of all, we have to think about the setting; this is a palliative setting. We often forget that we’re primarily palliating our patients with chemotherapy. But, of course, this again is a goal, and an important goal is to improve survival, so we really have to put both in balance. We can’t just think “I want to see a nice picture of a scan.” I want to actually take care of my patients—make sure that my patient ends up having the best quality of life along with a quantity of life. That’s why we have all these discussions sometimes about dose intensifications—Is it weekly, biweekly?—and others. I think that you really need to individualize your decisions based on the patient and based on these rational discussions, which sometimes are not that rational.

But the point is—and I agree with Eileen fully and everyone else’s input—that when you look at real-world data that come from the US Oncology database, that come from your study that you presented at ASCO GI, there’s a sense that if you sequence patients and you’re stuck with a doublet followed by a doublet, that your outcomes are very similar than if you actually throw what I call the whole kitchen sink. Now, that said, there’s a subgroup of patients that will benefit from FOLFIRINOX, more so. We talked about the COMPASS results. There are also those patients with the DDR, HRD, and definitely BRCA. They will benefit from the presence of the platinum and the irinotecan, but topoisomerases are active here, too.

So, I think—and this goes back to the point—we really need to know what the genetic profile of the tumor looks like and the genetic profile of the patient. And that may help us refine a little bit better, as we learn more and more whether we really need to expose patients to a 3-drug regimen, even if they have fantastic performance status. Even if they’re younger, that doesn’t mean that essentially the crime fits the punishment.

Transcript Edited for Clarity