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Personal Experience With Liposomal Irinotecan

Insights From: Tony Saab, MD, Mayo Clinic; Davendra Sohal, MD, MPH, Cleveland Clinic
Published: Thursday, Mar 07, 2019



Transcript: 

Tanios Bekaii-Saab, MD:
Now that we know that we have that option in the salvage setting, it makes a lot of sense to move it to the first-line setting. Just to track back a little bit, nanoliposomal irinotecan is a formulation of irinotecan. It’s a novel formulation of irinotecan, and it essentially packs a lot of irinotecan and liposome and allows that delivery to the bloodstream to the tumor to trickle down over about a week. So this actually circulates through for about a week. So it has a long half-life.

Theoretical advantage is of course you get more targeted delivery of the irinotecan. Because you’re packing 18,000 molecules of irinotecan in every nanoliposome, you don’t expect the toxicity profile to change much, so it’s primarily a delivery system than anything else. So it makes sense to bring this to the first-line. And there are 2 strategies that are being built around bringing nanoliposomal irinotecan to the first-line.

One is essentially looking at this regimen called Nanox with nanoliposomal irinotecan, oxaliplatin, and 5-FU [fluorouracil], which essentially is FOLFIRINOX [5-FU/irinotecan/oxaliplatin] but replacing the irinotecan with nanoliposomal irinotecan. The good news with this regimen is that you could essentially make the triplet less toxic figuring out a way to essentially adjust the dosages accordingly and make it equally effective. And there’s a study that’s looking at the combination of the triplet versus gemcitabine and nab-paclitaxel in the first-line.

Another study that is being considered is essentially going back to that concept of sequencing. And the importance of sequencing is thinking about strategies to take nanoliposomal irinotecan plus 5-FU, into the first-line given that it has very little cumulative toxicities, unlike gemcitabine/nab-paclitaxel where you can have neuropathy if you use the weekly regimen. I prefer the biweekly regimen where you essentially abrogate a lot of the issues with neuropathy, and that’s what I use in my clinic for all patients. And then the FOLFIRINOX, for the oxaliplatin, has the issues with the cumulative toxicity. So it makes sense with this principle of sequencing to bring it to the first-line.

The toxicities that we see around nanoliposomal irinotecan and 5-FU are very similar to what you would expect with FOLFIRI [folinic acid/fluorouracil/irinotecan], except for 1. We almost don’t see alopecia. In fact, only 20% of the patients will experience some level of alopecia. That’s probably the biggest difference between nanoliposomal irinotecan and irinotecan. The 2 have not been formally compared to each other in large settings, so we don’t know if there will be major differences. But at least in my practice, and I use a lot of FOLFIRI given the nature of our practice and the same with 5-FU/nanoliposomal irinotecan, I don’t see much of a difference between the 2 frankly.

I think it remains very important to consider educating patients about the risk of diarrhea, what it means, and how to preempt it, a good education about when to use loperamide and how frequently to use loperamide helps a lot. Because the biggest toxicity with all irinotecan compounds is diarrhea. And if you manage it well, patients actually go through it. In fact, many patients would prefer to have limited diarrhea than to have neuropathy, as long as they learn how to control it.

So I think that’s going to be key, sitting with the patient, doing the education, and allowing them to go through their tough journey with minimal toxicities if possible.

The other thing is, we just recently presented and are about to publish some data from NAPOLI-1 that’s looking at dose modifications, and if they affect or alter the outcome. And it turns out that no, you can really feel comfortable about modifying the dose of the drug according to guidelines and allow patients essentially to maintain a good outcome. I think that’s a very important thing. We’ve seen it also with gemcitabine/nab-paclitaxel in pancreas cancer. This is key for our patients to give them the comfort and the understanding that, hey, listen, don’t worry. If you hit the wall of toxicity, you don’t have to toughen up. We can bring it 1 notch down and it will still help you. So that allows the patients essentially to be more up front.

With neuropathy and diarrhea, you really don’t have a way to measure other than what the patient tells you. And oftentimes they hide it because they think that that drug is their lifeline. And if they cut down on the dose, or they tell you that they’re not doing well on it, you will essentially cut down on the dose and they will lose benefits. So I think it’s important to know that the data support those modifications as indicated and the outcome is not compromised. In fact, in some studies it makes it that the outcome may be better if you do the right thing for the patient, meaning adjust the dose accordingly.


Transcript Edited for Clarity

 
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Transcript: 

Tanios Bekaii-Saab, MD:
Now that we know that we have that option in the salvage setting, it makes a lot of sense to move it to the first-line setting. Just to track back a little bit, nanoliposomal irinotecan is a formulation of irinotecan. It’s a novel formulation of irinotecan, and it essentially packs a lot of irinotecan and liposome and allows that delivery to the bloodstream to the tumor to trickle down over about a week. So this actually circulates through for about a week. So it has a long half-life.

Theoretical advantage is of course you get more targeted delivery of the irinotecan. Because you’re packing 18,000 molecules of irinotecan in every nanoliposome, you don’t expect the toxicity profile to change much, so it’s primarily a delivery system than anything else. So it makes sense to bring this to the first-line. And there are 2 strategies that are being built around bringing nanoliposomal irinotecan to the first-line.

One is essentially looking at this regimen called Nanox with nanoliposomal irinotecan, oxaliplatin, and 5-FU [fluorouracil], which essentially is FOLFIRINOX [5-FU/irinotecan/oxaliplatin] but replacing the irinotecan with nanoliposomal irinotecan. The good news with this regimen is that you could essentially make the triplet less toxic figuring out a way to essentially adjust the dosages accordingly and make it equally effective. And there’s a study that’s looking at the combination of the triplet versus gemcitabine and nab-paclitaxel in the first-line.

Another study that is being considered is essentially going back to that concept of sequencing. And the importance of sequencing is thinking about strategies to take nanoliposomal irinotecan plus 5-FU, into the first-line given that it has very little cumulative toxicities, unlike gemcitabine/nab-paclitaxel where you can have neuropathy if you use the weekly regimen. I prefer the biweekly regimen where you essentially abrogate a lot of the issues with neuropathy, and that’s what I use in my clinic for all patients. And then the FOLFIRINOX, for the oxaliplatin, has the issues with the cumulative toxicity. So it makes sense with this principle of sequencing to bring it to the first-line.

The toxicities that we see around nanoliposomal irinotecan and 5-FU are very similar to what you would expect with FOLFIRI [folinic acid/fluorouracil/irinotecan], except for 1. We almost don’t see alopecia. In fact, only 20% of the patients will experience some level of alopecia. That’s probably the biggest difference between nanoliposomal irinotecan and irinotecan. The 2 have not been formally compared to each other in large settings, so we don’t know if there will be major differences. But at least in my practice, and I use a lot of FOLFIRI given the nature of our practice and the same with 5-FU/nanoliposomal irinotecan, I don’t see much of a difference between the 2 frankly.

I think it remains very important to consider educating patients about the risk of diarrhea, what it means, and how to preempt it, a good education about when to use loperamide and how frequently to use loperamide helps a lot. Because the biggest toxicity with all irinotecan compounds is diarrhea. And if you manage it well, patients actually go through it. In fact, many patients would prefer to have limited diarrhea than to have neuropathy, as long as they learn how to control it.

So I think that’s going to be key, sitting with the patient, doing the education, and allowing them to go through their tough journey with minimal toxicities if possible.

The other thing is, we just recently presented and are about to publish some data from NAPOLI-1 that’s looking at dose modifications, and if they affect or alter the outcome. And it turns out that no, you can really feel comfortable about modifying the dose of the drug according to guidelines and allow patients essentially to maintain a good outcome. I think that’s a very important thing. We’ve seen it also with gemcitabine/nab-paclitaxel in pancreas cancer. This is key for our patients to give them the comfort and the understanding that, hey, listen, don’t worry. If you hit the wall of toxicity, you don’t have to toughen up. We can bring it 1 notch down and it will still help you. So that allows the patients essentially to be more up front.

With neuropathy and diarrhea, you really don’t have a way to measure other than what the patient tells you. And oftentimes they hide it because they think that that drug is their lifeline. And if they cut down on the dose, or they tell you that they’re not doing well on it, you will essentially cut down on the dose and they will lose benefits. So I think it’s important to know that the data support those modifications as indicated and the outcome is not compromised. In fact, in some studies it makes it that the outcome may be better if you do the right thing for the patient, meaning adjust the dose accordingly.


Transcript Edited for Clarity

 
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