The Evolution of Sequencing Strategies in Pancreatic Cancer - Episode 9

Ongoing Neoadjuvant Clinical Trials in Pancreatic Cancer

Transcript:Johanna Bendell, MD: Eileen, we’ve talked about some new neoadjuvant approaches. The cooperative groups are looking at this, as well as some pharmaceutical companies. What trials are ongoing?

Eileen O’Reilly, MD: It’s an area of transition, in terms of the management of patients with localized pancreas cancer. Firstly, the recognition that some patients are potentially downstaged, whereas in the past, we would not have considered them candidates for the operating room. That’s changing.

There are a number of studies now, in the public network, looking at preoperative treatments. There’s the SWOG trial (the S1505), which is comparing gemcitabine and nab-paclitaxel and FOLFIRINOX in resectable pancreas cancer. And then there’s a parallel study in borderline resectable pancreas cancer that’s just opened, the Alliance trial, and this is using a backbone of modified FOLFIRINOX with plus or minus radiation.

But one of the learning points on this resectable study is exactly what you said. Even with multidisciplinary expertise, there’s still a lot of shades of gray in terms of where resectable ends and where borderline resectable begins. It’s a lot of judgment and interpretation, and I don’t think it’s necessarily consistent. So, these are hard. But I suspect what we’ll see happening (even though we don’t have data to support this yet) is that we’ll move to, irrespective of borderline or resectable, neoadjuvant-based treatments and surgery to follow. We’re still in a “surgery strong” institution, so it’s our default position in the absence of a trial. But clearly, this is a change that’s happening in pancreas cancer.

John Marshall, MD: We’re also seeing situations where you give some chemotherapy up front, and the imaging may be better, but still the radiologist is calling it unresectable. And then they go in and operate anyway. And it’s different than the imaging. So, I do think our default is to at least explore that patient even if we don’t think we’ve cleared the vessels like we think we have—unless there’s encasement or something like that. But if it’s a close call, we will err on the side of exploring that patient.

Johanna Bendell, MD: Yeah. And you think about these neoadjuvant regimens, both in patients who have resectable disease as well as borderline resectable disease. There’s a lot of questions out there as to how to optimize therapy. So, Caio, besides chemotherapy, tell us a little bit about the role that you see for radiation therapy for the treatment of these borderline resectable pancreas cancer patients.

Caio Max S. Rocha Lima, MD: Absolutely. I think this is a question that has not been answered yet. The role of radiation is being studied by the Alliance ongoing clinical trial. But the way radiation is given is novel, and in my opinion, it’s a better way to give radiation therapy. The old fractionation of 50 Gray given over 25 fractions, with big ports, may not be the best way to deliver radiation in pancreatic cancer. The optimal way may be by decreasing the number of fractions and by increasing the dose. And the Alliance trial is studying the role of tumor values of hyperfractionation. One is by SBRT (stereotactic body radiotherapy) that gives very narrow margins. Patients have to really have control of motion (taking deep breaths), so the high dose of radiation is going to be delivered to the cancer bed. The dose of that, in that protocol, is going to be 5.6 Gray over 5 days.

In institutions that cannot deliver SBRT, patients are going to be given the high fractionation with imaging guiding. It’s going to be a little bit of a lower dose (the tumor bed), but this is a higher dose than is given in the shorter period of time with the standard fractionation. And I think that’s going to pave the way to really understanding the potential benefits of radiation in this disease.

Johanna Bendell, MD: Eileen, tell us a little bit more about your experience with borderline resectable disease.

Eileen O’Reilly, MD: To follow on the point Caio just made, we want to know what radiation adds to in this setting. It may be one of the major settings in pancreas cancer where there is a clear utility in terms of affecting the ability to get a negative margin. And that’s, I think, very important. Some of these techniques may not truly optimize the oncologic effect against the tumor, but may facilitate getting that negative margin, which, from the oncologic point of view, is the optimal operation that you want to do.

So, answering this question, I think, is important. We’re struggling with where radiation fits in the adjuvant setting, and there’s a lot of controversy around whether we should or shouldn’t do it. We’ll hopefully have some data in the next few years, but this is in contrast to the LAPO7 study, which suggested that there may not be a role, routinely, for the use of radiation in locally advanced pancreas cancer. I just want to bring up the point that this is an important setting to consider the value of radiation in, and we have yet to declare whether it should be the routine standard in borderline resectable disease.

George Kim, MD: We really have to pay attention to quality assurance with the radiation, and the LAPO7 study results that were presented, I thought, were really interesting. The percent of radiation on protocol was 31%, and Dr. Abrams has been saying this for some time now (from the RTOG trial), that being on protocol is important in terms of outcome. I think the American experience is that our radiation colleagues do a good job of staying on the protocol, and that didn’t happen in LAP07. So, I don’t know if that’s a real answer, but we have to pay attention more and more to that.

John Marshall, MD: And that negative margin you mentioned, Eileen, is so important, right? Because if it’s not, then you might as well have not done the surgery in terms of outcome. So, it’s really important. And this is in the backdrop of an operation that actually, in the end, only cures a few people. We have to pick our spots and try to deliver all of that, because we know it translates into some significant morbidity. It’s a big deal operation. Pick the right patient. Get that negative margin.

Transcript Edited for Clarity