Clinical Research in the Treatment of Pancreas Cancer
Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Winson Y. Cheung, MD, MPH, University of Calgary and CancerControl Alberta; Manuel Hidalgo, MD, PhD, Harvard Medical School and Beth Israel Deaconess Medical Center; Ramesh K. Ramanathan, MD, Mayo Clinic; Tanios Bekaii-Saab, MD, FACP, Mayo Clinic; Thomas Seufferlein, MD, University of Ulm
Johanna C. Bendell, MD: So much work is being done to improve the cure rate of these patients. Some of these regimens have shown such benefit for the metastatic patients into the adjuvant setting. We are still trying to figure out what the sequence looks like, but a lot is happening here. There are a lot of ongoing trials trying to determine who’s going to best respond, and how well with these therapies.
Moving along to what I like to call the “dessert,” what’s coming, and what’s new? There is so much exciting stuff. Manuel, you have done so much in drug development, particularly in the field of pancreas cancer. I cannot wait to eat my ice cream and hear your take on what you see as promising, and upcoming, and what you’re seeing in your phase I units.
Manuel Hidalgo, MD, PhD: There is a lot of stuff out there, and I think what is important is that, for the first time, we’re starting to look at patient populations and not just entire groups of patients. A very important group is the DNA damage repair pathway group, which traditionally has been identified based on high family history. But, we’re learning more and more. Even unselected cases have germline mutations in some of the genes that compose the pathway.
So, the applicability of those panels, I think, is telling us that about 15% of the patients may have damage repair. And, of course, PARP inhibitors, ATR inhibitors—those are the drugs that I think are more important and interesting in that particular group. So, that is a very interesting area.
We haven’t talked about it much, but we will talk, probably before we finish, about immunotherapy and how it has been unlocked. There is a lot of interest in combining agents with checkpoint inhibitors to try to do that. The diversity of studies is very broad. The ones that we’re more interested in, but that doesn’t mean they’re going to be better, are CXCR4 inhibitors and CCR2 inhibitors. We even started talking about the microenvironment and how modulating the microenvironment with FAK-1 inhibitors, with pegylated hyaluronidase, may, at the end of the day, make the tumor hot for immunotherapy. So, I think that’s another big group of agents.
The STAT3 inhibitors—there is some very interesting data and a huge study being developed. We will see. CDK4/6 inhibitors are also actively in development. These are probably among the more exciting ones that I see out there. We continue to see studies come back negative. At The European Society for Medical Oncology (ESMO) 2017 Congress, we saw the OncoMed trial, the YOSEMITE trial. We spent probably 4, 5 years working in the lab with that compound, and we got very nice data. The study didn’t work. So, the story surfaced again.
Johanna C. Bendell, MD: It’s like in pancreas cancer...
Tanios Bekaii-Saab, MD, FACP: You always learn.
Johanna C. Bendell, MD: You always learn.
Manuel Hidalgo, MD, PhD: You always learn, yes. But one day you would like to learn by succeeding.
Tanios Bekaii-Saab, MD, FACP: I think from all the negatives came a lot of positives. We learned a lot along the way. There’s no negative study. There’s always a positive learning experience, one way or the other.
Johanna C. Bendell, MD: As stated by somebody that’s treated pancreas cancer for a long time. I think this sets a beautiful stage, and one thing that I want to clarify is, and I’m sure Manuel will agree with me, I can’t tell you how many patients come in to my clinic and say, “I want the Jimmy Carter drug, pembrolizumab, for my pancreas cancer.” I know you alluded to the combination, and the combination is so promising. But, for single-agent checkpoint inhibitors, and I want you to announce it to the world, do those work in pancreas cancer?
Manuel Hidalgo, MD, PhD: No, they do not. Except in the MSI group—the 0.5% that each one of us have seen in a couple of patients—no, they don’t work.