Potentially Curable Pancreatic Adenocarcinoma Guideline Update
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An interview with Dr. AloK Khorana from Cleveland Clinic on "Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update." This guideline update adds another treatment regimen to the options for patients with resected pancreatic adenocarcinoma who did not receive preoperative therapy. 

Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines 

See all of ASCO's podcasts at www.asco.org/podcasts 

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello, and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Alok Khorana from The Cleveland Clinic, lead author on "Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update." Thank you for being here today, Dr. Khorana. Thank you for having me. So this guideline was first published in 2016. And then we saw an update in 2017. And now we've just updated it again. So can you tell the listeners what has prompted these updates? In the world of pancreatic cancer, this has been an evolution in adjuvant treatment, which is sort of a surprise, because we've been treating pancreatic cancer in a very similar fashion over the past several decades. And between the 1990s and until just a few years ago, there hasn't really been much progress in terms of what to do with pancreatic cancer patients after they've had their cancer resected. It's pretty clear that these patients should not have just the surgery, that they should have additional treatment after the surgery. And for decades, the standard treatment after surgery was either 5-fluorouracil or gemcitabine, but most oncologists are opting for gemcitabine. The two recent updates of the ASCO Guidelines reflect two large randomized trials that have been published in this area. The first changed-- added a new standard of care, which was a doublet adjuvant therapy with gemcitabine and capecitabine. And the reason for this most recent update is the publication of a large randomized trial of adjuvant FOLFIRINOX for patients with pancreatic cancer that was published in December 2018 in "The New England." And we felt that the results were so compelling that we needed to update the guidelines so oncologists and practitioners would have the most current data to help them make decisions for patients. So for our listeners who may not now, can you tell us what changes have been made to the recommendations in this newest version of the guideline? So this is a guideline on a potentially curable pancreatic adenocarcinoma, which is we are saying these are resectable pancreatic cancer patients. And the guideline update changes primarily one recommendation, recommendation 4.1, which is a listing of additional adjuvant therapy options. As I mentioned earlier, the most common monotherapy option used to be the gemcitabine 5-fluorouracil. And that recently changed to doublet therapy. And we've kept those recommendations, but we've added the modified combination regimen of 5-fluorouracil, oxaliplatin, and irinotecan, which is known as the FOLFIRINOX regimen. And we are making this the preferred regimen for patients in the absence of concerns for toxicity or tolerance. We are still keeping the recommendations for the doublet therapy with gemcitabine capecitabine as well as monotherapy with gemcitabine alone or fluorouracil with cholanic acid. But those are not the preferred regimens, because the data for FOLFIRINOX is much better than prior regimens. Having said that, there are concerns about using such an aggressive regimen and in patients who have undergone a major surgery. So patients have not recovered from operation, then it's reasonable to consider one of the other regimens. But the update primarily focuses on adding adjuvant FOLFIRINOX as the preferred option in the adjuvant setting. And how has this guideline and its updates affected care for patients with pancreatic adenocarcinoma? I think since the results of this trial, the PRODIGY 24 trial came out of post-operative FOLFIRINOX. Almost every oncologist I know that focuses on treating patients with pancreatic cancer has suddenly added its use in patients that respected pancreatic cancer who are healthy enough to tolerate adjuvant FOLFIRINOX therapy. So it's definitely a practice-changing landmark paper. The results of the study were really quite impressive. The use of adjuvant therapy with FOLFIRINOX led to much longer survival than we've seen in any trial of adjuvant therapy of pancreatic cancer, almost 54 months-- or actually just over 54 months, almost 55 months-- in patients who are randomized to the modified FOLFIRINOX group and about 35 months in the gemcitabine alone group. The overall survival at three years was 63% in FOLFIRINOX and nearly 49% in the gemcitabine group. So that's a big difference at three-year survival as well. The one thing clinicians should be aware of is that this adjuvant therapy trial used a modified dose of FOLFIRINOX. They initially started off at the full those, which is 85 milligrams per meter squared of oxaliplatin, 400 mg per meter squared of leucovorin, and 180 milligrams per meter square of irinotecan. But the dose of iriniotecan was reduced part way through the study to 150 milligrams per meter squared, along with, of course, the conventional 2.4 grams or 5-fluorouracil over 46 hours. This modification of the irinotecan dose from 180 down to 150 is what many patients on the study received and was the more tolerable regimen and allowed the study to be completed. So the Guidelines Panel felt quite strongly that when using FOLFIRINOX in the adjuvant setting, we should stick with this modified dose, which is a lower dose of irinotecan at 150 milligrams per meter squared. And I think it's important that clinicians be aware of this distinction. And so taking this into account, many of us have made this recommendation to patients who are healthy enough to tolerate adjuvant FOLFIRINOX. And the hope is that this guideline will inform this ongoing practice as it changes in response to new data. And finally, what trials or new research are you keeping an eye on that may prompt an update for this guideline in the future? The results of another large adjuvant therapy trial are expected, hopefully at ASCO this year. This trial is the APAC trial that utilizes gemcitabine and nab-paclitaxel or Abraxane. This doublet combination is quite widely used in patients with metastatic pancreas cancer, particularly those patients for whom we feel FOLFIRINOX may not be appropriate because of their performance status or functional status. And the hope was that the doublet combination would also have good success in the adjuvant therapy setting and perhaps be a better option than the gem-cape doublet. There has been a press release from the sponsor of that trial, and it looks like the trial was not successful, although the way the press release is worded is rather confusing. So we wait for the full results of that trial to be presented at ASCO before we have an understanding of whether that is an appropriate regimen to use or not in the adjuvant setting. So that's certainly one large trial that many of us have been looking forward to complete sort of the set of ongoing adjuvant therapy trials in this setting. Great. It sounds like there's some really exciting things happening in pancreatic cancer right now. And I look forward to seeing this guideline evolve with the research. So Dr. Khorana, thank you so much for coming on the podcast today and summarizing the Potentially Curable Pancreatic Adenocarcinoma: ASCO Clinical Practice Guideline Update. Thank you, Shannon. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

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