Meet The Professors: Pancreatic Cancer Edition, 2016 - Video 39Role of checkpoint inhibitors for patients with pancreatic cancer
7:15 minutes.
TRANSCRIPTION:
DR TEMPERO: I understand the dilemma that you find yourselves in, and we also, often we have enough data that we can say — maybe it hasn’t been published yet, but we happen to know that outside of, say, mismatch repair defects, it’s unlikely — in fact, studies have shown that there are no responses. So patients don’t want to do something that is totally futile most of the time if you can find some option for them. So one thing that I will often suggest is, if nothing else is available, “Why don’t you try curcumin?” Curcumin is a spice, right? There’s actually some data with oral curcumin. I even have a patient who I believe benefited from oral curcumin. It’s not going to hurt them. DR LOVE: Hold on. What is it? DR TEMPERO: Curcumin. DR LOVE: Curcumin? What is it? DR TEMPERO: Spice. DR LOVE: Spice? DR TEMPERO: Spice. Yes. Commonly found in curry and things like that. DR LOVE: And it’s been tested in scientific — DR TEMPERO: There were tests, studies at MD Anderson. They had trouble getting a uniformly bioavailable product. And so they’re still working on formulation on it. I don't know, Tony, if you know any more than that about it. DR BEKAII-SAAB: Yes. And that’s one of the most challenging — DR BEKAII-SAAB: Powder. They can pack it into a pill. DR TEMPERO: Put it in a capsule. DR LOVE: Where do they get it? I mean, the trial, but can people access this? DR BEKAII-SAAB: Yes. DR TEMPERO: You can go to your supermarket. DR LOVE: And like how much — what kind of preparation? DR TEMPERO: Nobody knows what the right dose is. And often it’s as much as tolerated, because it can cause diarrhea. DR BEKAII-SAAB: It’s very erratic in terms of its absorption. DR TEMPERO: Yes. DR BEKAII-SAAB: It’s a very problematic agent. I mean, preclinically it looks wonderful. It looks like it’s the cure for cancer. But the reality is that this is work that now is ongoing for 20 years and has not panned out into anything of significance, clinically. DR TEMPERO: Only because I think they don’t have a way to give the drug. The point I’m making, though, is, it’s trying to find an option for them. And we try very, very hard. Maybe it’s something as trivial as that, or maybe it is seeing our Phase I specialists and finding something that is a good match for them at the early development level. DR LOVE: So a patient who’s in relatively good health comes to see you for a second opinion. The general oncologist has said, “We’ve run out of options. Maybe you should consider a checkpoint inhibitor.” They’re not eligible or don’t want to participate in the trial. They’re coming to you to consider taking — they can pay for it. Do you say, “Don’t do it”? DR TEMPERO: I do, because those drugs can have a lot of toxicity, too. So I try to find them some idea that they can pursue. I’m not insensitive to the fact that they really, really want — if they have a good performance status and they really, really want to try something, I’ll try to find something for them. But I don’t like to see a patient waste their resources or take any risks for something that has very little benefit, in fact proven not of benefit. DR BEKAII-SAAB: Except in a small subset. If you have the MSI. But there is also another subset of patients that could potentially — haven’t been looked at — could potentially have some benefit, maybe not from just single agent but from these immunotherapeutic strategies, are those with BRCA mutations that are genomically unstable. And they’re more likely to actually respond to immune therapies. Again, I mean, you have to look at these specific populations eventually, as you develop these strategies. But I agree with Margaret. For the overwhelming majority of patients, single-agent approaches don’t seem to have much benefit. I still think that there’s a role for immune therapy, though, in pancreas cancer, but it’s not single-agent PD-1. In fact, it’s a bunch of stuff, so combination immunotherapeutics or sequencing chemotherapeutics or radiation with these inhibitors, so essentially creating neoantigens, exposing the tumor to damage before applying these PD-1 inhibitors. DR LOVE: I can’t remember hearing a connection — I’m not even sure I know of data of people with BRCA. Breast cancer, for example, ovarian and checkpoint inhibitors. Have you seen data on that or is that theoretical? I don’t remember seeing that. DR SCHWARTZ: It has something to do with mutational load. DR LOVE: Yes. I know, but I mean theoretically. But, I mean, I’m trying to remember actual treatment, BRCA patients. DR TEMPERO: There is unpublished data. DR LOVE: There is? Unpublished. Yes, because I know I’ve seen checkpoint inhibitors, for example, in breast cancer. I don’t remember even that they looked at BRCA. DR BEKAII-SAAB: So if you look at a number of other cancers, like biliary cancer, they seem to be quite susceptible. And again, you have to do those studies. DR LOVE: Interesting. DR BEKAII-SAAB: They seem to be pretty susceptible to immune therapy. And a lot of it has to do with 30%-plus. The same, by the way, with gastric cancer. More than 30% to 40% of them are genomically unstable, mostly BRCA driven. DR LOVE: Gastric is MSI. DR BEKAII-SAAB: MSI, but with MSI and mutational load. But there’s also the BRCA-driven or BRCAness, more than BRCA genomic instability. So just MSI itself doesn’t justify the level of response you see in a lot of these patients. A good chunk, yes. But biliary cancer, the same again. You have this genomic instability, hypermutations associated with that, and higher susceptibility to immune therapies. Again, whether that’s going to work or not in pancreas cancer we don’t know yet. Whether you can induce that state with chemotherapy, like FOLFIRINOX or gemcitabine/nab paclitaxel and SBRT or other forms of radiation, these are being looked at. And they make theoretical sense. But in practice yet, we don’t have that data. DR TEMPERO: But this discussion also informs our discussion earlier in terms of trying to get the genomic interrogation done as early as possible in the course of the patient’s treatment. DR BEKAII-SAAB: Absolutely. DR TEMPERO: Because then, when you come around to these very difficult decisions, you’ll actually have more to inform you. DR BEKAII-SAAB: Yes. DR TEMPERO: Was there BRCA in the tumor or not? Is it MSI high or not? So you have all that information when you’re making those difficult decisions down the line. DR BROOKS: We can do MSI in house with the more simple studies. But think about genomic load and, later on, do you have experience — and we’ve been talking. I’ve got some interest in liquid biopsies and have been sending quite a few out. Is that something you’re using? DR BEKAII-SAAB: It’s coming. DR BROOKS: And, also in pancreatic cancer, as they go along, do you want to use tissue that you’ve had a long time or a year ago, or do you want to look at something — DR BEKAII-SAAB: So in ovarian, you already have a liquid signature. That’s developed. In pancreas, it’s in the works. So you’ll have a liquid signature for BRCA/BRCAness that will — and there is also a genetic signature that’s being developed for not MSI but looking at hypermutated tumors that may link to MSI, so an indirect way of assessing MSI through liquid samples. So this is coming. |