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Adjuvant 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
Published: Monday, Oct 30, 2017



Transcript: 

Johanna C. Bendell, MD: Let’s transition and discuss that 20% of patients who don’t present with systemic disease. We know that surgery is the only way to cure these patients, who often have micrometastatic disease that we can’t detect. There has been a lot of discussion lately, and Tony and I were just at a fascinating meeting where we listened to some surgeons talk and I’m now completely taken with some of your Mayo Clinic surgeons. Tell me about the multidisciplinary approach to these patients and how you now define—because it’s changing and evolving—the resectable patient versus the borderline resectable patient?

Tanios Bekaii-Saab, MD, FACP: Really, at this point, the way you want to think about it—before you think about a discussion, because the surgeon, ultimately, and the results will, help you decide—there’s the resectable, the borderline, and the unresectable. The clearly resectable patients are those that are free of any involvement or abutment of any blood vessels or major vessels or celiac plexus. And then, the borderline resectable are those that are somewhat in the gray zone. You’re not sure that you’re going to get a clear R0 resection, but you think there’s a 50% chance you may. So, you clump them in that borderline category. And the clearly unresectable are those that involve the superior mesenteric artery and celiac plexus—just wrap around it completely. And that takes us, essentially, to the importance of all of this. Even in that white, black, and gray area, there’s still a lot of grayness. This is why it’s incredibly important for those patients to be assessed. Every single one of them needs to be assessed in a multidisciplinary setting with a surgeon, radiologist, and the medical oncologist.

Johanna C. Bendell, MD: I think, and I want to get into this discussion in a minute, there’s this whole concept of going with a neoadjuvant approach rather than straight to surgery in the resectable patient. But before we go there, I want to talk a little bit more about the data that we’ve seen for adjuvant therapy for pancreas cancer. Manuel, what have we used? What are you using now? There’s a little controversy going on, and there’s a randomized phase III study that we’re waiting on for a readout (which will hopefully happen relatively soon).

Manuel Hidalgo, MD, PhD: There is the FOLFIRINOX study, as well, and that is completely enrolled. We have the APACT study and the FOLFIRINOX study that are about to be released, as well as ESPAC-4, which was published a few months ago, actually. In the adjuvant setting, we have moved away from radiation. We’re not using radiation in any form—neither external beam, nor SBRT, nor CyberKnife. Most patients are getting gemcitabine and capecitabine these days. ESPAC-4 is a study that is complicated to understand. To me, it’s very clear that in the R0 resection group of patients, the benefit appears to be quite substantial. In the R1 resection group of patients, which was about 70% of the patients, the benefit of adding capecitabine is not that impressive. That’s number 1. Number 2 is that, and I don’t know how much detail we need to get into, it’s very interesting that the study was powered to detect a hazard ratio of 0.74, right?

Johanna C. Bendell, MD: Yes.

Manuel Hidalgo, MD, PhD: The hazard ratio is 0.82. The P values are still significant. I think that with how the statistics work; it’s still a little bit of an enigma. There is no difference in the 2-year survival. The projective 5-year survival is better, but that’s projected. We need to wait for the follow-up. So, I think that gemcitabine and capecitabine is a good drug regimen. It’s more toxic, of course. I think it’s a good regimen, but there are still some patients that could be managed with gemcitabine, alone. And, of course, if we were in Japan, we would be using S-1s. But, we are not, right?

Johanna C. Bendell, MD: Yes.

Thomas Seufferlein, MD: The important thing is that patients get adjuvant treatment. That’s what we can clearly say from all the trials. In ESPAC-4, what I take is that it’s the right way. That combination may confer additional benefit, but we don’t know whether this is the optimal combination. We will see the data, and maybe we’ll have to identify the subgroup of patients that really benefit from this treatment. The problem with adjuvant therapy is we only treat those who can get it, and this is down to 50% (postoperatively) because of perioperative morbidity. This is one of the problems. We’re already selecting the good ones, in this case.

Manuel Hidalgo, MD, PhD: There are a lot of issues because, of course, these studies have been conducted over the past 15 years and things have changed, fortunately. Something that changed is the management of metastatic disease. The survival differences that we see now are because we have better regimens when the patients relapse. Perhaps their relapses are being detected even earlier, as we monitor them more aggressively. And we’re treating oligometastatic disease in a much more aggressive manner than we did before. So, it’s all complicated.

Johanna C. Bendell, MD: I still have a lot of people that send patients to me for second opinions. They’re using gemcitabine and nab-paclitaxel, early, as adjuvant therapy. We’re waiting for results from the APACT study. Winson, can you tell us a little bit about APACT?

Winson Y. Cheung, MD, MPH: We’re all waiting anxiously for the results. I think we’re optimistic that it might show some improvement. For the time being, we haven’t jumped on board, yet, and adopted that therapy. I agree with Manuel. Right now, gemcitabine and capecitabine is a standard in Canada for the adjuvant setting. There is a very little role for radiation in Canada as well. It’s not used very heavily at all. So, until we see phase III evidence, we haven’t really extrapolated and done that.

Transcript Edited for Clarity 

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Transcript: 

Johanna C. Bendell, MD: Let’s transition and discuss that 20% of patients who don’t present with systemic disease. We know that surgery is the only way to cure these patients, who often have micrometastatic disease that we can’t detect. There has been a lot of discussion lately, and Tony and I were just at a fascinating meeting where we listened to some surgeons talk and I’m now completely taken with some of your Mayo Clinic surgeons. Tell me about the multidisciplinary approach to these patients and how you now define—because it’s changing and evolving—the resectable patient versus the borderline resectable patient?

Tanios Bekaii-Saab, MD, FACP: Really, at this point, the way you want to think about it—before you think about a discussion, because the surgeon, ultimately, and the results will, help you decide—there’s the resectable, the borderline, and the unresectable. The clearly resectable patients are those that are free of any involvement or abutment of any blood vessels or major vessels or celiac plexus. And then, the borderline resectable are those that are somewhat in the gray zone. You’re not sure that you’re going to get a clear R0 resection, but you think there’s a 50% chance you may. So, you clump them in that borderline category. And the clearly unresectable are those that involve the superior mesenteric artery and celiac plexus—just wrap around it completely. And that takes us, essentially, to the importance of all of this. Even in that white, black, and gray area, there’s still a lot of grayness. This is why it’s incredibly important for those patients to be assessed. Every single one of them needs to be assessed in a multidisciplinary setting with a surgeon, radiologist, and the medical oncologist.

Johanna C. Bendell, MD: I think, and I want to get into this discussion in a minute, there’s this whole concept of going with a neoadjuvant approach rather than straight to surgery in the resectable patient. But before we go there, I want to talk a little bit more about the data that we’ve seen for adjuvant therapy for pancreas cancer. Manuel, what have we used? What are you using now? There’s a little controversy going on, and there’s a randomized phase III study that we’re waiting on for a readout (which will hopefully happen relatively soon).

Manuel Hidalgo, MD, PhD: There is the FOLFIRINOX study, as well, and that is completely enrolled. We have the APACT study and the FOLFIRINOX study that are about to be released, as well as ESPAC-4, which was published a few months ago, actually. In the adjuvant setting, we have moved away from radiation. We’re not using radiation in any form—neither external beam, nor SBRT, nor CyberKnife. Most patients are getting gemcitabine and capecitabine these days. ESPAC-4 is a study that is complicated to understand. To me, it’s very clear that in the R0 resection group of patients, the benefit appears to be quite substantial. In the R1 resection group of patients, which was about 70% of the patients, the benefit of adding capecitabine is not that impressive. That’s number 1. Number 2 is that, and I don’t know how much detail we need to get into, it’s very interesting that the study was powered to detect a hazard ratio of 0.74, right?

Johanna C. Bendell, MD: Yes.

Manuel Hidalgo, MD, PhD: The hazard ratio is 0.82. The P values are still significant. I think that with how the statistics work; it’s still a little bit of an enigma. There is no difference in the 2-year survival. The projective 5-year survival is better, but that’s projected. We need to wait for the follow-up. So, I think that gemcitabine and capecitabine is a good drug regimen. It’s more toxic, of course. I think it’s a good regimen, but there are still some patients that could be managed with gemcitabine, alone. And, of course, if we were in Japan, we would be using S-1s. But, we are not, right?

Johanna C. Bendell, MD: Yes.

Thomas Seufferlein, MD: The important thing is that patients get adjuvant treatment. That’s what we can clearly say from all the trials. In ESPAC-4, what I take is that it’s the right way. That combination may confer additional benefit, but we don’t know whether this is the optimal combination. We will see the data, and maybe we’ll have to identify the subgroup of patients that really benefit from this treatment. The problem with adjuvant therapy is we only treat those who can get it, and this is down to 50% (postoperatively) because of perioperative morbidity. This is one of the problems. We’re already selecting the good ones, in this case.

Manuel Hidalgo, MD, PhD: There are a lot of issues because, of course, these studies have been conducted over the past 15 years and things have changed, fortunately. Something that changed is the management of metastatic disease. The survival differences that we see now are because we have better regimens when the patients relapse. Perhaps their relapses are being detected even earlier, as we monitor them more aggressively. And we’re treating oligometastatic disease in a much more aggressive manner than we did before. So, it’s all complicated.

Johanna C. Bendell, MD: I still have a lot of people that send patients to me for second opinions. They’re using gemcitabine and nab-paclitaxel, early, as adjuvant therapy. We’re waiting for results from the APACT study. Winson, can you tell us a little bit about APACT?

Winson Y. Cheung, MD, MPH: We’re all waiting anxiously for the results. I think we’re optimistic that it might show some improvement. For the time being, we haven’t jumped on board, yet, and adopted that therapy. I agree with Manuel. Right now, gemcitabine and capecitabine is a standard in Canada for the adjuvant setting. There is a very little role for radiation in Canada as well. It’s not used very heavily at all. So, until we see phase III evidence, we haven’t really extrapolated and done that.

Transcript Edited for Clarity 
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Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Integrating Novel Targeted Treatment Strategies to Advance Pancreatic Cancer CareNov 30, 20181.0
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