Neoadjuvant Therapy Recommendations in 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: I’m very curious to see how everybody in different countries around the world treats patients in the neoadjuvant setting. Certainly, within the United States, it’s a little bit more controversial, although I think it’s becoming more standard, with pancreas cancer being thought of as a systemic disease. And, in fact, it is.
Before you take somebody to the operating room, do you do a neoadjuvant approach? Do you do a neoadjuvant approach with just chemotherapy? Or, do you include radiation therapy (that way you get the treatment in)? If 50% of patients don’t get adjuvant therapy, they get it beforehand.
Winson, in Canada, what is your approach to these patients that come in, even with resectable disease?
Winson Y. Cheung, MD, MPH: Neoadjuvant therapy is probably used most extensively in the borderline resectable population. If they’re clearly resectable, the trend is still to have them go to surgery right away. As you mentioned, it is quite controversial. There are some surgeons and oncologists who would favor a neoadjuvant approach. So, that’s kind of the extent of its use. It’s not used very, very heavily at all, actually.
Johanna C. Bendell, MD: So, in these borderline patients, what’s your approach? Which chemotherapy do you use? Do you use radiation? Do you use it all?
Winson Y. Cheung, MD, MPH: I don’t use radiation very much. In terms of the decision between FOLFIRINOX or gemcitabine and nab-paclitaxel, it comes down to that patient’s performance status. If they’re very young, fit, and compliant, then there’s a tendency to use FOLFIRINOX. If they’re a little older and less fit, then I usually favor gemcitabine and nab-paclitaxel. Again, we really don’t have local experience. And the rate of downstaging, for example, is actually very, very rare. So, again, it kind of calls into question whether there is a true role for neoadjuvant therapy until a trial proves its efficacy.
Johanna C. Bendell, MD: That’s very interesting. Manuel, what do you guys do in Boston?
Manuel Hidalgo, MD, PhD: If it’s a clearly resectable patient, it’s resection followed by chemotherapy. For borderline and locally advanced patients, we classify them but we manage them the same way, with the difference that locally and borderline is going to go to surgery unless there is progression. They are technically resectable if you do vascular reconstruction. So, they’re going to be resected. Usually, they get chemotherapy—FOLFIRINOX or GA (gemcitabine/Abraxane). You have a first look. If downstaged, sometimes they go to surgery, early. Otherwise, they get SBRT (stereotactic body radiation therapy) followed by more chemotherapy and, then, surgery. So, you do surgery.
In the course of the 6 to 7 months, surgery often occurs at the end. The median survival of these patients is in the 22-, 23-plus month range. You get a decent 60%, 70% margin-free resection in the true borderline scenario.
Now, locally advanced is the same management, but surgery is an exception. And I think that the LAPACT data (of 30%)—I don’t know the numbers, but I think it’s a little bit lower. The patients that are able to...
Tanios Bekaii-Saab, MD, FACP: It was about 15%.
Manuel Hidalgo, MD, PhD: Locally advanced is also on a spectrum. The real T4 tumors with celiac trunk encasement—those never go. The tumors are classified because there is more than 180 degrees of SMA (superior mesenteric artery). That’s a different story because they can do vascular reconstruction. So, these are 2 very different groups with regards to surgical potential.
Johanna C. Bendell, MD: I can’t wait to hear what the Germans do.
Thomas Seufferlein, MD: In our system, it’s a bit difficult because it’s a bit different. Our surgeons are a little bit more aggressive. And, in our guidelines, we define borderline differently because venous involvement will not count as borderline, but, clearly resectable. They say, “The data outcome is the same, so why should we differentiate?”
I’m running a trial in Germany—a multicenter trial on neoadjuvant treatment of clearly resectable disease with gemcitabine/Abraxane, in this case. There is a good rationale for doing that for neoadjuvant treatment, but we need to educate surgeons that this is a sensible idea and you shouldn’t resect straightaway. And, of course, we don’t have the data to do it out of a trial. I think we need to run the trial, and we need to tell patients that 20% of patients will progress on the neoadjuvant treatment. There is a debate that surgeons say, “We could have saved this patient.” And I say, “This is the patient that should not have been operated on in the first place.” We select those who will actually not benefit. So, this is for the clearly resectable disease.
For the locally advanced, we are running 2 different trials. One is a chemotherapy trial where we have FOLFIRINOX plus gemcitabine/Abraxane, in exchange, for these patients. When they are stable or downsized on imaging, they need to be surgically explored. It’s compulsory because imaging lets us down. When we decide on doing an aggressive treatment (and doing chemotherapy is also an aggressive treatment), then we need to explore them surgically.
We have another trial running where you have a chemotherapy induction in those who are stable. Then, they undergo either radiotherapy or chemotherapy (in locally advanced disease). Then, they get surgically explored, if they are still stable. But with the rate of chemotherapy in locally advanced disease, even when you’re talking about SBRT, you say, “Now we have more aggressive protocols.” But we don’t know (I don’t think), because we have better chemotherapy protocols, and that may actually completely obliterate an additional effect of radiotherapy. Maybe, but we don’t know. So, we can see it both ways. I think we need to do it in trials. It’s an optimistic way of saying, “It’s locally advanced. Let’s irradiate.” That’s something we don’t do. We will do it to control pain, where you really need to do that for pain control, but not as a standard.
I think we need to run the appropriate trials, also, with more modern radiochemotherapy schemes—better planning of radiation treatment. Maybe SBRT works, but it’s not done at very many sites in Germany because it’s toxic. You need to really be very, very precise in your planning. It needs attention from a dedicated radiotherapist. You need to have somebody that loves doing pancreas. There are not that many, particularly in Germany, because it’s not so popular. There is some potential, but it’s definitely not standard for us.