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Advances in Adjuvant Chemotherapy

Insights From: Tony Saab, MD, Mayo Clinic; Davendra Sohal, MD, MPH, Cleveland Clinic
Published: Tuesday, Feb 19, 2019



Transcript: 

Tanios Bekaii-Saab, MD:
So 2018 was a fantastic year, I think, for pancreatic cancer in early stage because of the PRODIGE 24 study that compared essentially modified FOLFIRINOX versus gemcitabine in the adjuvant setting. For the longest time, gemcitabine had been our standard, and then gemcitabine and capecitabine seem to take it 1 notch up. And then we have the results of the study with modified FOLFIRINOX versus gemcitabine in the adjuvant setting, and the result was just short of amazing for pancreatic cancer. Survival was up to 50-plus months from 30 months with gemcitabine. And then the disease-free survival at the median was 21 months. With gemcitabine alone, it’s about 12 months.

Now interestingly, the study truly reflects what we would expect from gemcitabine, in terms of progression-free survival or disease-free survival. All the studies, the CONKO study, looked at gem versus observation and had a median disease-free survival of about 11 months. So this is very close. It’s good to see that, because our control arm behaves similarly to all old controls.

The survival with gemcitabine was 30 months, which was very interesting. And that’s consistent. Now more and more, we see gemcitabine in the adjuvant setting producing results that are higher than expected. And the reason is not that gemcitabine is a better drug, because disease-free survival is about the same. It’s all these good salvage regimens we have after patients fail adjuvant therapy, such as FOLFIRINOX, gemcitabine, nab-paclitaxel, 5-fluorouracil and nanoliposomal irinotecan, Alfieri.

So these are salvaging patients and increasing the survival. But what we see with FOLFIRINOX is almost doubling of the median disease-free survival. And a survival that certainly outmatches gemcitabine by far, 50-plus months. And in pancreatic cancer years, that’s a lot. We like it. We want to see better, but we like it. It’s a good study. It tells us we can change how this disease behaves.

So today, modified FOLFIRINOX is the standard of care for all patients who are able to receive it. It’s still a rough regimen. There were a lot of toxicities as you would expect with FOLFIRINOX. You have to be very selective. You know, would you give it to a patient who’s older than 70 or 75? The answer is probably not, at least above 75. Between 70 and 75, you’d be judicious about it. A lot of these patients are pretty beat after their surgery, and it’s very tough to give them any form of therapy. And so these patients may not be able to go through FOLFIRINOX. So unfortunately it doesn’t apply to everyone.

I think we have a solution, though, to improve exposure, and that’s to move all this treatment to the neoadjuvant setting. We call this total neoadjuvant therapy. That may essentially change the course for more patients who may not be able to get it after surgery.

Davendra Sohal, MD, MPH: Adjuvant chemotherapy has also certainly evolved in pancreatic cancer, in the last 1 to 2 years, in fact. It used to be adjuvant gemcitabine single agent, or perhaps 5-fluorouracil single agent. And now it has become gemcitabine-capecitabine since ASCO [the American Society of Clinical Oncology] presentation in 2017, followed by the publication of the study. The gemcitabine-capecitabine doublet, however, increases median overall survival from 25.5 to only about 28 months—still a meaningful, statistically significant improvement, but it comes at the cost of toxicities.

More recently, however, just last month we had a publication following up on the presentation of data from the PRODIGE 24 study of FOLFIRINOX in the adjuvant setting. And that has shown a remarkable progress. The median overall survival, for example, increased from 35 to 54 months, which is unheard of, greater than 4 years, 4.5 years, approaching median overall survival in resected pancreatic cancer. So that certainly has become the frontline option now.

The caveat is that it is an aggressive regimen. It comes with a lot of toxicities, especially in the postoperative setting. So patient selection is key. And in the real-world setting, we’ll have to see how FOLFIRINOX pans out in the sense of deliverability of the regimen for 6 months.

The APACT is an interesting question that’s still out there. Gemcitabine, nab-paclitaxel versus gemcitabine alone for chemotherapy used for adjuvant treatment of pancreatic cancer that has been resected. As I mentioned, gemcitabine and capecitabine is a standard of care. FOLFIRINOX now is probably the standard of care, and we’ll see where gemcitabine and nab paclitaxel falls. Whether it is comparable to these regimens will have to be seen. The toxicities will have to be understood well. We cannot compare trial head-to-head of course, but we will probably get a sense. And it might actually honestly end up being like the metastatic setting where there are 2 options—FOLFIRINOX and gem and nab-paclitaxel.


Transcript Edited for Clarity 
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Transcript: 

Tanios Bekaii-Saab, MD:
So 2018 was a fantastic year, I think, for pancreatic cancer in early stage because of the PRODIGE 24 study that compared essentially modified FOLFIRINOX versus gemcitabine in the adjuvant setting. For the longest time, gemcitabine had been our standard, and then gemcitabine and capecitabine seem to take it 1 notch up. And then we have the results of the study with modified FOLFIRINOX versus gemcitabine in the adjuvant setting, and the result was just short of amazing for pancreatic cancer. Survival was up to 50-plus months from 30 months with gemcitabine. And then the disease-free survival at the median was 21 months. With gemcitabine alone, it’s about 12 months.

Now interestingly, the study truly reflects what we would expect from gemcitabine, in terms of progression-free survival or disease-free survival. All the studies, the CONKO study, looked at gem versus observation and had a median disease-free survival of about 11 months. So this is very close. It’s good to see that, because our control arm behaves similarly to all old controls.

The survival with gemcitabine was 30 months, which was very interesting. And that’s consistent. Now more and more, we see gemcitabine in the adjuvant setting producing results that are higher than expected. And the reason is not that gemcitabine is a better drug, because disease-free survival is about the same. It’s all these good salvage regimens we have after patients fail adjuvant therapy, such as FOLFIRINOX, gemcitabine, nab-paclitaxel, 5-fluorouracil and nanoliposomal irinotecan, Alfieri.

So these are salvaging patients and increasing the survival. But what we see with FOLFIRINOX is almost doubling of the median disease-free survival. And a survival that certainly outmatches gemcitabine by far, 50-plus months. And in pancreatic cancer years, that’s a lot. We like it. We want to see better, but we like it. It’s a good study. It tells us we can change how this disease behaves.

So today, modified FOLFIRINOX is the standard of care for all patients who are able to receive it. It’s still a rough regimen. There were a lot of toxicities as you would expect with FOLFIRINOX. You have to be very selective. You know, would you give it to a patient who’s older than 70 or 75? The answer is probably not, at least above 75. Between 70 and 75, you’d be judicious about it. A lot of these patients are pretty beat after their surgery, and it’s very tough to give them any form of therapy. And so these patients may not be able to go through FOLFIRINOX. So unfortunately it doesn’t apply to everyone.

I think we have a solution, though, to improve exposure, and that’s to move all this treatment to the neoadjuvant setting. We call this total neoadjuvant therapy. That may essentially change the course for more patients who may not be able to get it after surgery.

Davendra Sohal, MD, MPH: Adjuvant chemotherapy has also certainly evolved in pancreatic cancer, in the last 1 to 2 years, in fact. It used to be adjuvant gemcitabine single agent, or perhaps 5-fluorouracil single agent. And now it has become gemcitabine-capecitabine since ASCO [the American Society of Clinical Oncology] presentation in 2017, followed by the publication of the study. The gemcitabine-capecitabine doublet, however, increases median overall survival from 25.5 to only about 28 months—still a meaningful, statistically significant improvement, but it comes at the cost of toxicities.

More recently, however, just last month we had a publication following up on the presentation of data from the PRODIGE 24 study of FOLFIRINOX in the adjuvant setting. And that has shown a remarkable progress. The median overall survival, for example, increased from 35 to 54 months, which is unheard of, greater than 4 years, 4.5 years, approaching median overall survival in resected pancreatic cancer. So that certainly has become the frontline option now.

The caveat is that it is an aggressive regimen. It comes with a lot of toxicities, especially in the postoperative setting. So patient selection is key. And in the real-world setting, we’ll have to see how FOLFIRINOX pans out in the sense of deliverability of the regimen for 6 months.

The APACT is an interesting question that’s still out there. Gemcitabine, nab-paclitaxel versus gemcitabine alone for chemotherapy used for adjuvant treatment of pancreatic cancer that has been resected. As I mentioned, gemcitabine and capecitabine is a standard of care. FOLFIRINOX now is probably the standard of care, and we’ll see where gemcitabine and nab paclitaxel falls. Whether it is comparable to these regimens will have to be seen. The toxicities will have to be understood well. We cannot compare trial head-to-head of course, but we will probably get a sense. And it might actually honestly end up being like the metastatic setting where there are 2 options—FOLFIRINOX and gem and nab-paclitaxel.


Transcript Edited for Clarity 
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