Emerging Approaches: Pancreatic Cancer Systemic Therapy - Episode 5

Borderline Resectable & Locally Advanced Cases

February 20, 2019

Transcript: Davendra Sohal, MD, MPH: There are many definitions about the resectability of pancreatic cancer, and we are evolving toward the intergroup definition used in the National Clinical Trials Network. The prior definitions used to be subjective, such as abutment, involvement, and encasement of the vessels. And the intergroup definition tries to define resectability based on the geometric interface between the tumor and the vessel walls. The veins and the arteries are assessed on cross-sectional imaging, and we define the circumference of the vessel wall and interfacing with the tumor. Borderline resectable is defined broadly as venous involvement more than 180 degrees but arterial involvement less than 180 degrees, and locally advanced is defined as arterial involvement more than 180 degrees. And of course, there has to be absence of metastatic disease in these assessments.

Tanios Bekaii-Saab, MD: So for borderline resectable pancreatic cancer, the standard is neoadjuvant therapy. I mean, arguably there are some patients who you may take to surgery, but there’s a high likelihood of an R1 resection, and in some ways there will never be a chance for a cure. So to enhance the capacity of an R0 resection for borderline resectable, we have to consider chemotherapy. I’m not sure if we really need radiation. We had a previous study that we published that suggested that more than half the patients will never need radiation. In fact, those who needed radiation are those where it was still very strongly borderline, borderline.

So selectively, maybe, for some patients, but for most, radiation doesn’t have a role in the adjuvant; chemotherapy, definitely. The choice would be modified FOLFIRINOX for most patients. For others it would be gemcitabine, nab-paclitaxel. Locally advanced is a much tougher disease, of course, as we’ve heard. This is a disease that is not technically resectable. So clearly unresectable at least at diagnosis.

We know that there are a few patients, though, who end up going to surgery. In fact, more and more of them, 10% to 20% of those patients are able to go to surgery when they have no chance of resection prior. And the question is, how do we treat those patients? How do we do it? How do we get them? How do we shepherd them to surgery? Or to improve the outcomes?

So again, similar to borderline resectable, the question of modified FOLFIRINOX versus gemcitabine, nab-paclitaxel arises. We know that modified FOLFIRINOX has been established in this role. There are a number of publications that support that. Recently we’ve heard the results of LAPACT study with gemcitabine. Nab-paclitaxel looked very interesting: a 35% response rate and a number of patients who were able to get to surgical resection with R0 resection as well.

So I think we have 2 options in this disease setting—FOLFIRINOX and gemcitabine—nab-paclitaxel. Then the next question, of course, is whether there’s a role for radiation. I’d say only if the patient is a candidate for resection. If the patient will never be resected, I don’t think there’s any role for radiation, and we should not expose those patients unnecessarily to radiation. For patients, those 10% to 20% who may end up in surgery—and the surgeon will be able to tell you who those patients are a good surgeon—those patients may be exposed to radiation to increase the chances of an R0 resection. That’s the only time we do it.

Now the question of modified FOLFIRINOX versus gemcitabine and nab-paclitaxel in this setting, that’s a tougher question because they’ve never been compared. Similar to borderline resectable, they’ve never been compared. I think historically they look very similar, and I frankly don’t think I have a major preference for 1 versus the other, given the results of LAPACT.

Davendra Sohal, MD, MPH: That’s a very important question, how to decide between the use of FOLFIRINOX or gem, nab-paclitaxel or other options for first-line treatment of metastatic pancreatic cancer? A couple of years ago we came out with ASCO’s [the American Society of Clinical Oncology’s] guidelines for the treatment of metastatic pancreatic cancer, and we tried to define in as much granular details as possible, the reasons to choose 1 regimen versus the other. The frontline option, the primary option remains FOLFIRINOX for “the perfect patient.” An ECOG [Eastern Cooperative Oncology Group] performance score of 0 or 1; no significant comorbidities; adequate organ function, and interest and agreement to use chemotherapy pumps, chemotherapy ports and infusion pumps.

For a slightly softer case, for example, with some comorbidities perhaps, and an inclination not to use chemotherapy port or infusion pumps, and the ability to modify the treatment regimen a little easier, gem, nab-paclitaxel would be the frontline option.

Transcript Edited for Clarity