DR BROOKS: Since I think our experience is pretty limited with the liposomal, a couple of questions: (1), is there any difference in the infusional-related toxicities where we have to use atropine sometimes with irinotecan? And (2), do you have any different limitations with bilirubin adjustments as opposed to irinotecan?

DR LOVE: Tony, I’ll let you handle that one.

DR BEKAII-SAAB: Yes. So I don’t think we disagree when you talked about the diarrhea. In fact, I agree with the fact that you see less of, the cholinergic effect — and, therefore, less likely to use atropine in this setting to get less crampy. And it’s probably because the irinotecan peaks later with the infusion.

DR LOVE: Can I just ask one before — I’ve got to ask, it’s kind of rolling around in my — that targeted thing. So can you talk more — I mean, when you were talking, I was thinking about antibody-drug conjugates, like T-DM1, delivering into tumor cells. What actually happens?

DR BEKAII-SAAB: So when the liposome actually reaches the site involved with the tumor, so the vasculature “gradient” essentially will lead to that leakage from the nanoliposom —

DR LOVE: It’s trapped in there or something?

DR BEKAII-SAAB: Just leaks.

DR LOVE: Leaks.

DR BEKAII-SAAB: Yes, leaks. The irinotecan leaks into the tumor. The liposome actually stays in the circulation and goes around and around. And every time it hits, it just gives a little dose of the irinotecan and SN-38.

DR LOVE: So in some way it’s targeting the tumor? Or is it the anatomy of it?

DR BEKAII-SAAB: Again, theoretically ye —

DR LOVE: Margaret, what’s your take on it?

DR TEMPERO: Nobody knows for sure, but there’s a lot of data to show retention in tumor-associated vasculature.

DR LOVE: We were talking about second-line therapy or therapy after FOLFIRINOX. Is there any situation where you would use it after FOLFIRINOX, Tony?

DR BEKAII-SAAB: The only time that I would use it after FOLFIRINOX is if we’ve used FOLFIRINOX in the neoadjuvant setting or, say, adjuvant setting, which I don’t. But there’s the study in France that’s looking at that. And then if there’s at least a 6-month period before the cancer progresses, then I would consider it, although you still have gemcitabine and nab paclitaxel as the choice. But that would be the only time I would use it.

DR TEMPERO: No, I agree with that.

DR BROOKS: Just the question about the bilirubin. It’s a nitty-gritty question that we face every day.

They’ve had a stent. Their bilirubin is 1.7 or 2.1. Is there any difference — or maybe you could tell us how you would handle the dosing of either irinotecan or the liposomal.

DR LOVE: Margaret?

DR TEMPERO: We wait until the bilirubin is normal or near normal to start treatment. So if they’ve had a stent, we just wait until there’s full decompression. We will not use it if we can’t do that.

DR LOVE: Tony?

DR BEKAII-SAAB: So again, there are 2 ways: (1), it’s normal, or (2), it’s definitely trending down within a week. If it’s twice the upper limit of normal, I’m comfortable with the iri or with the nal-IRI. So the magic number is twice the upper limit of normal of bili.