Progress and Promise in Advanced Pancreatic Cancer - Episode 12
Transcript:Johanna Bendell, MD: What do we have if people don’t have access to a phase I unit, what are the big next comer trials that are going on right now? What are the next agents that people are looking at for patients with pancreas cancer? Philip, can you tell us about some of those?
Philip A. Philip, MD, PhD: Johanna, I remember at ASCO last year in June, there was a presentation of a drug called PEGylated hyaluronidase, which is the human recombinant form. Basically, you have the cancer cells in the pancreas, and all of us know when you look under the microscope, there’s a lot of dense stroma there, but also there’s this matrix which is like a shell. It’s like a turtle shell underneath protecting the cancer cells. So, when you give the chemotherapy—and this is a simplistic way of explaining it, but that’s really what it is—getting into those cancer cells to kill them is a problem. And we’ve known that for a long time. The blood vessels get also compressed because of that. This drug, which dissolves the hyaluronan—and you can measure this expression in the tumors—allows the blood vessels to open up. And there is clinical evidence from two very good experiments done by two very highly regarded scientists, and published in high impact journals, that show that it works when you combine it with chemotherapy in pancreatic cancer. So, that went into pilot trials, and now there are a couple of randomized phase II trials—one of them I’m involved with at the SWOG, combining FOLFIRINOX with a drug.
There’s a study done nationally, combining gemcitabine/nab-paclitaxel with the drug. And the presentation last year, in June, by Sunil Hingorani, with few patient numbers—it’s still a study that is ongoing and we have more mature data—indicated that the combination of the drug plus gemcitabine/nab-paclitaxel doubled time to progression, and doubled the response rate in patients who had overexpression of the hyaluronan. And the company has really worked very fast in developing a validated assay for it, immunohistochemistry. There’s a protocol out there, which I received it as an invitation to join a phase III trial in patients who have only an elevated level of expression, combining the drug versus nab-paclitaxel/gemcitabine as control. So that, at this point in time, is of a lot of interest for us, not only because I’m involved in the other trial, but simply the data so far have shown interest. Now, we have to do the phase III trial. In fact, we can’t use it, it’s not available for us, but we have to do the phase III trial.
George P. Kim, MD: But I think it has the added benefit that you have to use Lovenox to reduce some of the arterial or venous events. I think most of the trials now are using 1 mg/kg BID Lovenox, which is actually a therapeutic dose, to help reduce some of those events.
Johanna Bendell, MD: And really quickly, tumor inflammation, the JAK inhibitors. I think we’re waiting on readout there.
Thomas A. Abrams, MD: I think the real promise there is that you can maybe influence symptomatology with these drugs. By reducing inflammation in these high CRP patients, you may in fact make them feel better. They may have less fatigue, and less anorexia. And so, you may be influencing their disease in a symptomatic fashion, as well as maybe enhancing their responses. I think that’s a really interesting way of treating the disease.
George P. Kim, MD: We’re also seeing some anti-cachexia agents coming forward. I don’t want to keep saying his name, Tony Saab, but he’s got some interesting data with HDAC inhibitors that he presented, so that will also be helpful.
Johanna Bendell, MD: So, certainly, who would have ever thought we’d have treatment options to discuss for patients with pancreas cancer. I mean, there will be controversy about what to use when. Finally, we’re able to sequence. And if you really look at it, we’ve probably doubled survival for patients with metastatic disease over the last couple of years. That’s very impressive, and, hopefully, we’ll be translating that into curing more patients. It’s a huge area for research, a very exciting area, and lots of clinical trials that are available. PanCAN also has a clinical trials matching service for patients, so that’s also very nice if you have patients that are looking for studies.
Transcript Edited for Clarity