Advances in the Treatment of Pancreatic Cancer - Episode 15
John Marshall, MD: We’re also clinical researchers up here, and we are trying to develop new medicines. Please tell me there’s something good coming out.
Shubham Pant, MD: I think there are a lot of exciting agents coming out in phase III trials right now. There’s PEGPH20 [pegvorhyaluronidase alfa]. The phase III trial is running right now. There’s a STAT3 phase III trial that’s running. There’s another pyruvate metalloproteinase.
There are a number of drugs that are coming out in the frontline. I think the biggest thing is—when I talk about research in the early phase—patient selection. If we select just third-line patients for some of these trials, it’s very hard. Earlier patient selection is very important when they’re fit enough to get it, and I do think looking at the tumor microenvironment is a big 1. You have to break through that shell to get into it.
When I talk to researchers, I say, “Think about it like chicken soup. You have chicken soup in which you have the chicken chunks, and you have the soup, and you have to get through.” I say it at lunch talks. I show a can of 1 of the chicken soups, and I say, “This is what we’re up against.” There are a lot of preclinical data in pancreatic cancer. It’s been well documented that we can kill a lot of cell lines very easily. When we put it into patients, it is so different because of all the stroma and everything around it. It’s so different, and that’s why these drugs, which look beautiful in preclinical modeling, really don’t pan out, unfortunately. We really need, exactly as Allyson is saying, better preclinical model organoids in which we can replicate the stroma to actually find the agents that can fight this disease.
John Marshall, MD: Along that line, is there any role for prophylactic anticoagulation in these patients?
Paul Oberstein, MD: In this clinical trial—the PEGPH20—there were very high rates of blood clots.
John Marshall, MD: That’s to prevent at therapy. I’m just talking about…
Edward Kim, MD: In that trial.
Paul Oberstein, MD: In that trial, it was absolutely critical to give prophylactic anticoagulation, and it made a big difference. The bigger question is people who were not on that trial, or until we get a readout, and there certainly are patients who have a high rate of blood clots—those with superhigh CA 19-9 [carbohydrate antigen 19-9] or those who have been relatively immobile. Data have shown that you can reduce the risk of blood clots but not necessarily change outcomes.
Edward Kim, MD: In that trial, the phase II study with GEM [gemcitabine]—nab-paclitaxel and PEGPH20, it stopped the trial for a period of time, because the rate of thrombosis was close to 50%. Even in the control arm with just chemotherapy and GEM–nab-paclitaxel—those are our other patients—was 25%. Both groups were subsequently treated, after the pause, with low-molecular weight heparin, and that lowered their rates to less than 10% for both groups. It’s a high rate, but the problem is the increased risk of bleeding and other outcomes that you also alter.
John Marshall, MD: In the new oral agents, it’s a little less.
Paul Oberstein, MD: Do you use it?
John Marshall, MD: I have not adopted it. I have to tell you: I want to. I see these patients, and I think 1 in 4, maybe 1 in 5, is going to come in with a PE [pulmonary embolism]. It’s that Friday afternoon CT [computed tomography] scan with a PE.
Shubham Pant, MD: The CASSINI trial had a subset of patients with pancreatic cancer. It’s at this year’s ASCO [American Society of Clinical Oncology Annual Meeting] with 1 of the oral anticoagulants. There was definitely a decrease in blood clots in patients with pancreatic cancer. There was not an increased risk of bleeding, so that’s very important. Also, that can be causing more harm than good. There was no increased risk of bleeding. There was a statistically significant decreased risk of blood clots, but we don’t know if that makes patients live longer. That part is not there, but we know that if we want to give it, you have an argument to give it. That means you don’t have an increased risk of blood clots or bleeding, and you have fewer blood clots, but we don’t know if it’s going to improve survival in the end.
Transcript Edited for Clarity