The Evolution of Sequencing Strategies in Pancreatic Cancer - Episode 11

Adjuvant Therapy in Pancreatic Cancer

Transcript:Johanna Bendell, MD: So, the patient goes to the operating room and has their resection. George, what do you want to do?

George Kim, MD: I want to give them chemotherapy.

Johanna Bendell, MD: Really?

George Kim, MD: Yes.

Johanna Bendell, MD: What kind of chemotherapy? That’s the question.

George Kim, MD: Recently at ASCO, there was a presentation by our colleagues from the UK. It was regarding the ESPAC 4 trial, and it showed that the combination of capecitabine with gemcitabine was superior to gemcitabine in the postoperative setting. I think that has become the standard in the United States. It’s an interesting trial, so I think it’s reasonable to give capecitabine. In the trial, it was 1660 mg/m2 per day. So, what is it, 830 mg/m2 twice a day? Patients were given capecitabine for 21 out of 28 days and they did pretty well. Seventy-eight percent of patients were able to tolerate the capecitabine, and the gemcitabine was also well tolerated.

So, there’s some problems that I have with the trial—60% were R1 resections. That’s a big number. We’ll have to see if that is real. We know they don’t use a lot of radiation in the UK or at least we know that the quality, again, may be in question. That’s important. In the future, though, we’ll have more information about Abraxane-gemcitabine from the APACT trial; that study’s been completed. It was accrued in 2 years, so hopefully we’ll have that data very soon.

We also have the FOLFIRINOX regimen. The French are doing that. They’ve taken up the bolus. They reduced the irinotecan by 20%. We tried to bring that to the US, but we were not successful. But we’ll have to see what that trial does. I think, unfortunately, they are selecting patients in that study. So, it’s a slow accrual and we’ll have the same debate: is it better to use Abraxane-gemcitabine or FOLFIRINOX in the adjuvant setting? No matter what, at least we’ll have moved the field forward in having treatments that are available.

But for today, I think capecitabine-gemcitabine is a very reasonable regimen. Again, I’d be careful with your PPIs (proton pump inhibitors) because there’s an interaction that’s being reported more and more between capecitabine and those agents. And as you know, most patients that come out of surgery are on PPI. So, just, again, we should consider patient management issues.

Johanna Bendell, MD: And that’s if the PPI makes the capecitabine less effective?

George Kim, MD: Potentially.

Johanna Bendell, MD: We’ve touched on locally advanced pancreas cancer. John, does your treatment approach change for locally advanced? We’ve talked a little bit about the role of radiation (plus or minus), but does that change your choice of chemotherapy? Let’s say this is somebody that’s not going to go to resection.

John Marshall, MD: I’d still probably use the same parameters I would use for a metastatic patient, quite honestly—age, performance status—and factor that in. So, I’d probably use gemcitabine, then paclitaxel, and then why would I not? There will be some cases when I might not.

Johanna Bendell, MD: Okay. Eileen?

Eileen O’Reilly, MD: For the truly locally advanced and unresectable, the question for me is whether or not to use radiation in that group. But the idea of consolidating and the idea of providing an opportunity to stop treatment and watch and monitor, I think that’s a nice goal. And as we all know, these patients get tired. Six months of these heavy duty cytotoxic regimens is wearing for even the fittest of the fittest. So, I’m a little uncomfortable with just stopping after chemotherapy (on its own) because I think the probability is that it’s not going to result with a sustained disease control for too long.

And you know, your group’s approach is intriguing, right? Low-intensity treatment on an ongoing basis and trying to push off the inevitable, but maintaining a quality of life at lesser toxicity, I think it’s a strategy that, maybe, we need to explore more in pancreas cancer. In metastatic disease, after we’ve debulked patients and have gotten their disease under control, maybe this is a setting where we can, for some, ease off the pressure but maintain some level of treatment.

Johanna Bendell, MD: We’ve seen some interesting data. There’s an abstract at this year’s GI ASCO meeting that’s looking at gemcitabine and nab-paclitaxel in the local advanced setting and doing the approach that all of you suggested along the way, which is giving some chemotherapy and then potentially consolidating with radiation therapy versus continuing on with the chemotherapy. And I think as that study and more studies like that come through, we’ll get more of a sense as to whether or not this radiation consolidation helps for these patients.

Eileen O’Reilly, MD: Yes. The LAPACT study, or Locally Advanced Pancreatic Cancer Trial study, was evaluating that theme. We had 1 unfortunate failure in the cooperative group systems last year, which was a very similar study using 3 gemcitabine nab-paclitaxel backbone regimens in locally advanced disease, looking at intensifying the radiation versus chemotherapy versus standard—but it didn’t accrue.

Transcript Edited for Clarity