Any Role for Immunotherapy in Pancreatic Cancer?

Transcript:

John Marshall, MD: We’ve only got a couple of more minutes to go, but sadly that’s all we need to discuss immuno-oncology [I-O] in pancreatic cancer. If you look at the other ones, that’s all they talk about. We save it for an afterthought, in some ways. Allyson, when the MSI [microsatellite instability] story came out, 1 of the advocacy groups put on its website, “A new drug for pancreas cancer,” which stayed up only a day or so before we asked them to take it down. MSI does occur in pancreatic cancer. It’s not common.

Allyson Ocean, MD: I’ve never seen 1, actually.

John Marshall, MD: We have 1. I think there were 8 on Dung Le’s study in the overall panel—about an 80% response rate. Do you have 1?

Paul Oberstein, MD: Three or 4. Three for sure. I can’t remember if I have a fourth.

Shubham Pant, MD: Which side of New York…

John Marshall, MD: This is a little cluster.

Paul Oberstein, MD: One was a Lynch syndrome, and 2 were sporadic. One was an 84-year-old woman.

John Marshall, MD: When I think about NTRK, I think about MSI. These are rare events. The challenging question I ask myself is, if I didn’t have tissue, would I biopsy a patient just for those 2 assays? If they’re positive, it could be transformative.

Allyson Ocean, MD: I think if they had a strong cancer family history, but if this is a 1-off cancer and the chance of you finding MSI-high or even high TMB [tumor mutational burden], I think, is…

Paul Oberstein, MD: The rates are incredibly low.

Allyson Ocean, MD: Yes, incredibly low.

Edward Kim, MD: Is it being tested on some of the liquid biopsies now? I have a recently diagnosed patient, through a liquid biopsy, of MSI high.

John Marshall, MD: Very cool. It’s worth looking if you can. I think we’re all in agreement there. You’ll never find the Willy Wonka golden ticket if you don’t buy some chocolate bars, so you have to open the chocolate bars. Is there anything new anybody has in the I-O space, or combinations that we’re starting to see some benefit with?

Shubham Pant, MD: Well, 1 of the potential problems is, a lot of patients do come to us and say, “I want immunotherapy,” and then we have to explain to them—

John Marshall, MD: They all say that.

Shubham Pant, MD: We have to explain to them what it means, and that with the immune checkpoint inhibitors, the response is 0% as single agent in pancreatic cancer. You cannot go lower than 0%.

John Marshall, MD: If you find 1, it’s probably because they’re MSI high.

Shubham Pant, MD: I do think, if we try to again make a cold tumor hot, how do we do it? There’s a lot of literature about moving the macrophages from M2 to M1. We a have recently concluded trial with a second-line colony-stimulating factor 1 receptor [CSF1R] agent.

John Marshall, MD: I have a patient on a study with that combination now.

Shubham Pant, MD: That’s an agent. There’s data from Paul’s institution, NYU Langone Perlmutter Cancer Center, about RIP1 kinase inhibition, also. I think we’re making strides in it, so we just need to keep on looking and keep on putting more patients on trial, and maybe earlier on, not when they’re in third line and they’ve got a low albumen and they’re getting taps. Normally those patients don’t get through the first month of clinical trials.

Paul Oberstein, MD: I think once you find it, it will be obvious. One of the challenges is that there have been a lot of negative trials that have not been reported in immunotherapy in pancreatic cancer.

John Marshall, MD: Zero for 10, or 0 for 20.

Paul Oberstein, MD: We just don’t know. I think, at this point, we just don’t have it.

Edward Kim, MD: There is also the CD40, which looks like an interesting target.

Allyson Ocean, MD: Is that the Penn Pancreatic Cancer Research Center group?

Edward Kim, MD: Parker Institute for Cancer Immunotherapy.

Allyson Ocean, MD: Yes, with Parker-Penn. That looked very intriguing.

John Marshall, MD: Outside clinical trials, I get questions from doctors who say, “Should I just throw the Hail Mary? Should I call up the insurance company and try I/O in pancreatic cancer?” I’m seeing a lot of heads nodding. No, don’t do it.

Shubham Pant, MD: Don’t do it.

John Marshall, MD: It’s false hope, I think. It’s cost; it’s toxicity with very little to zero chance. Is that fair?

Allyson Ocean, MD: That’s right.

John Marshall, MD: We agree on 1 thing. I have to tell you, you guys are awesome. You’re smart people, and I really think you’ve been fabulous to join me today. This has really been extremely informative, but before we end this, I’m going to give you guys 1 more chance at a final thought. Dr Kim, you’re starting. What’s your summary of what you would say to folks out there about pancreatic cancer?

Edward Kim, MD: Stay tuned. This is an exciting time. To have this much to talk about in pancreatic cancer is—I can talk about pancreas all day, anyway, but this is just really exciting. I think it’s fantastic that we have this many things to argue and chew on and talk about. There’s just more to come.

John Marshall, MD: Talking about pancreas all day—I want to party with you. Paul, you’re next.

Paul Oberstein, MD: Although I’m the eternal optimist, the reality is that we have very few treatment options for pancreatic cancer. We should use the ones we have. Everyone should get them, but we really need patients to go on clinical trials and report those trials and get better therapies.

John Marshall, MD: Join the club, the PanCan [Pancreatic Cancer Action Network]. Be part of the answer. Allyson, what are your thoughts?

Allyson Ocean, MD: I want everyone to know that there is treatment, and they have to get treatment. We are working day and night to get better treatments, and we will get there. We still have a huge way to go, but if a physician tells you, “Oh, I’m sorry. I can’t help you. Get your affairs in order. We can’t make a difference,” that’s not true. You have to find another doctor, because we do have treatments, and as Paul said, we should use them. Make sure that your family also knows about this disease that you have, because it could be genetic.

John Marshall, MD: Last word.

Shubham Pant, MD: People ask me, “How can you do pancreatic cancer?” It’s tough, but I think that’s the great thing about it. There is so much to do. There is so much we can use to move the needle. The patients are amazing, and the families are amazing. They know they’re faced with a tough diagnosis. They show up trying to say, “We want to go on a trial. We want to do something about this disease.” I think we really need to, as we’ve all said, just get more patients on clinical trials. I think we are at the tip of the iceberg. There are so many new agents being tested for the first time that I’ve seen in the last 3 or 4 years in pharmaceuticals. There are things like Precision Promise, which is coming from PanCan. I think people are really investing. I just think we need smarter trials. We do 1000-patient trials in pancreatic cancer. That is not the right way to do the trial. That’s a lot of wasted of patient resources and patients’ time. We need smarter trials. We need more adaptive designs to get the answer early. I think that’s where we really move the needle in this disease.

John Marshall, MD: That’s terrific. You guys are awesome. We want to thank you for joining us today, and I hope you found this OncLive® Peer Exchange® discussion on pancreatic cancer to be useful and informative.

Transcript Edited for Clarity