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: Winson, Manuel alluded to this—immunotherapy combinations and this whole concept of turning a cold tumor into a hot tumor. Can you tell us a little bit about that?
Winson Y. Cheung, MD, MPH: In my prior life, in Vancouver, before I moved to Calgary, I actually treated melanoma. So, I’ve seen that when it works, it works very, very well. I think we’re all still very hopeful that maybe different combinations might do the trick. We’re kind of crossing our fingers and hoping for the best because when it works, it works extremely, extremely well.
Johanna C. Bendell, MD: Yes. Thomas, what’s your take on that?
Thomas Seufferlein, MD: I think there is some potential, but we need to find the way to combine immunotherapy, immuno-oncology, with the other respective drugs that actually make it work well. Maybe there are bifunctional antibodies that will give us a better answer by really forcing the immune system into the tumor? I think simple checkpoint inhibition is probably not going to work. We need additional components.
Johanna C. Bendell, MD: Yes, and even chemotherapy combinations, probably. Do you think we’ll probably need more than that with immunotherapy?
Thomas Seufferlein, MD: Most likely. Even adding on MEK inhibition might not really be sufficient. We will learn that, and we need to do the trials. We need to really do smart trials to get the answers quickly. We need to not involve too many patients who do not benefit. But then again, we shouldn’t try everything we have just as a Rubik’s Cube approach. And we need to, of course, rely on basic science that really gives us at least some clues as to where to go.
Johanna C. Bendell, MD: You bring up such an important point. Clinical trials have become so complicated. I get push back from people that are trying to put patients on the study saying, “Why do I have to get this fresh biopsy for this study? Why do I have to do this?” And I think my answer back to them is, “This is what clinical trials are, now. We’re trying to learn.”
So, even if we have a negative study, we’re going to learn something from those biomarkers and realize that there may be some patients that will benefit more than others. We need to know who those patients are. In trying to reinforce that, even though clinical trials are becoming more complicated, there’s a method to our madness. We’re bringing it all in, today. No stops.
If you were a betting person going to Vegas, what do you think will give us the most benefit for pancreas cancer in the next 5 years? I’m going to start with Thomas.
Thomas Seufferlein, MD: Well, in the neoadjuvant setting, we know who benefits. We’ll treat those patients in a neoadjuvant setting. They will have a 5-year overall survival rate of above 50%, 60%.
Johanna C. Bendell, MD: Wow, shoot high. Wow, you’re tough.Tony?
Tanios Bekaii-Saab, MD, FACP: I think the biggest bet is that we’re ultimately going to be able to break this disease down into multiple subgroups. It’s very clear that the BRCA, BRCA-ness group is one group. The MSI-high [microsatellite instability-high] group, although very small, is another. Those, we know. The MSI-high group—it’s a slam dunk. But for the BRCA, again, with the right agents, we will be able to move the needle significantly. And with the others, we’ll have to see. There are a couple of interesting and promising agents that are making their way into pancreas cancer.
Johanna C. Bendell, MD: Ramesh?
Ramesh K. Ramanathan, MD: I think somebody will find a key to immunotherapy use in pancreatic cancer, not in MSI, but maybe 30%, 40%, 50% costimulatory molecule, vaccines. I think that will be a big breakthrough with immunotherapy in pancreatic cancer. It has to happen. If it can happen in melanoma, why not in pancreatic cancer?
Johanna C. Bendell, MD: Winson?
Winson Y. Cheung, MD, MPH: I think we’re learning that pancreatic cancer is a very heterogeneous disease, and I think it is really about enriching the right patient subsets and targeting therapies to these individual groups. It is not about treating all-comers as one disease. I think that’s where the focus should be.
Johanna C. Bendell, MD: Manuel, your bet?
Manuel Hidalgo, MD, PhD: Well, everything has been said, but I think that if we had a good RAS inhibitor, perhaps we could provide some improvement.
Johanna C. Bendell, MD: Yes, a lot of developments are going on there.
Manuel Hidalgo, MD, PhD: Yes, a lot.
Johanna C. Bendell, MD: It’s very exciting. My personal projection for new approaches? I think it’s going to be a combination of immunotherapy with a microenvironment drug. But we’ll see.
Guys, this has been so informative. I’m so thankful to have you all on the panel, here, with me. I’m going to go through everybody again and ask for some final closing thoughts on what you think people should take away from this panel. Manuel, what would you say people should take away from this?
Manuel Hidalgo, MD, PhD: I think that my summary message is not to give up on the patients too soon. Multidisciplinary care is critical. To identify the patients that can be treated with either adjuvant or neoadjuvant curative approaches is critical. So, multidisciplinary care and, then, enrolling patients into clinical trials with good and new combinations is what eventually will make a difference in this disease. We have made some progress. There’s an opportunity where we will make more progress if we continue working together and incorporating new strategies.
Johanna C. Bendell, MD: Winson?
Winson Y. Cheung, MD, MPH: Well, I think it’s exciting times because many things are going on. But earlier, a few of us had also mentioned that in the current trials, the vast majority are young patients who are ECOG performance score 0 and 1. As a health outcomes researcher, I think about the routine patients that we see in clinic. It would be nice to see more pragmatic trials where ECOG 2 individuals, and older people, were enrolled as well. And, along the same lines, it may be nice to see some outcomes or population-based studies that look at how agents that are proving to work in clinical trials are actually being used in real life.
Johanna C. Bendell, MD: Ramesh?
Ramesh K. Ramanathan, MD: I think pancreatic surgery should be done in a specialized center. I think the guidelines say that there are at least 18 to 20 pancreatic surgeries per year. That’s not a very high bar but, amazingly, there are not many centers in the United States that do that kind of volume. So, at least for surgery, I would say to please refer patients to a center with experience.
Johanna C. Bendell, MD: Very good. Tony?
Tanios Bekaii-Saab, MD, FACP: Inclosing thoughts, I think this is a much better time to be taking care of patients with pancreas cancer. I think we can provide our patients with more hope, now, than ever, and more hope for the future.
Johanna C. Bendell, MD: Thomas?
Thomas Seufferlein, MD: I agree with all that’s been said. To me, it’s important. With the era of genomics, we have to put patients, whenever and wherever, into trials. But we also have to take an effort to collect bio materials. We rely on those to really make decisions, in the future, on treatment. And when we don’t have a trial which has enough bio material, tissue, urine, blood, or whatever, we need to collect and have that. This is an extra effort, but it’s worthwhile. Then, we can take the consequences.
Johanna C. Bendell, MD: An overall message of promise and hope. Thank you, all of you, for contributing to the discussion. I think this was a great panel. On behalf of our panel, we thank you for joining us and we hope you found this Peer Exchange® discussion to be useful and informative.