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Trifluridine/Tipiracil in Advanced Colorectal Cancer

Panelists: John Marshall, MD, Lombardi Comprehensive Cancer Center; Alan P. Venook, MD, Helen Diller Family Comprehensive Cancer Center; Tanios Bekaii-Saab, MD, The Mayo Clinic; Johanna Bendell, MD, The Sarah Cannon Research Institute
Published Online: Monday, Mar 20, 2017



Transcript:

John Marshall, MD:
Johanna, I’m going to ask you to start about managing the trifluridine/tipiracil, or TAS-102. The schedule, the dose, it’s a little complicated, and the side effects. How are you doing it?

Johanna Bendell, MD: So, we talked about oral treatments. I think one of the biggest things I talk to my patients about is just because these are pills, doesn’t mean that they can’t be dangerous. I think a lot of patients think, “Oh, I’m taking a pill.” They think it’s like a multivitamin, so I’ve seen people miss a dose a lot. And so, there’s a lot of education that goes when you’re trusting the patient to take these certain pills. One of the things that I try to do for my TAS-102 patients is I say, “Monday through Friday, Monday through Friday, 2 weeks off.” Because I think it’s easier for them to remember Monday through Friday than trying to count out 5 days and 2 days. For some patients, they want to start on a different day and I say, “Mark it on your calendar.” So, we talk a lot about treatment calendars. What we see with TAS-102, and as Tony alluded to, is mostly neutropenia as the biggest side effect. And, in fact, there have been data published that suggest that the more neutropenia that you have or treatment delays due to neutropenia, the better you’re going to do on the TAS-102, which is ironic. That doesn’t say take more. But what I do is often times—and I think for a good chunk of the patients, maybe 20% to 25%—I end up delaying it. It becomes, instead of a 4-week cycle, a 5-week cycle. So, I tend to just give them a little extra time off rather than dose-reduce and try to keep them more at full dose.

John Marshall, MD: I don’t use a lot of growth factor in my practice. Is this a place you think about it?

Johanna Bendell, MD: Yes, I’ve seen people do it. The timing is right to do it. Have I done it before? A couple of times where people really fell low and it was more than a 1-week delay.

John Marshall, MD: And then, do you do anything funky with the 2 pills sizes? Now that you’ve got this 5-day on, 2-day off schedule and 2 pill sizes, what do you do?

Johanna Bendell, MD: I never use both pill sizes, I round. I do the same thing with capecitabine. I think it’s too confusing for patients to figure out, “How many of these pills do I take versus how many of those pills do I take?”

John Marshall, MD: You guys are going to get mad at me, but I tend to believe VEGF inhibition is a good thing. And when I give this drug, I try to keep the bevacizumab going. Anybody else with me?

Alan P. Venook, MD: Well, of course, if you’re using regorafenib, you probably are continuing the anti-VEGF. I’ve actually evolved to believe that as well. I do think, in many patients, there’s an apparent rebound from the discontinuation of bevacizumab. We see that after all in the TML study, which there was not a huge difference in outcome, but clearly in earlier line. And so, I actually do agree with you. I think the truth is that many folks in the community do it, and I’ve come to believe that, in fact, it may be a difference maker for some patients.

John Marshall, MD: And, of course, we’re going to get more data, right? These drugs are moving earlier, combinations are being done.

Tanios Bekaii-Saab, MD: Well, I think that we do have earlier data with 5-FU and bevacizumab in third-line, which essentially seem to add very little benefit or not.

John Marshall, MD: But, to be fair, it’s not randomized discontinuation, so it’s not against a placebo.

Tanios Bekaii-Saab, MD: Understood, but when I look at even bevacizumab beyond progression when you get to second-line, you lose significant benefit already. So, I’m not sure that I would venture down that way with minimal data. I can’t say that it’s wrong. I just think that I wouldn’t use it in clinic before I see more convincing data.

John Marshall, MD: Every time I think about it and do it, I’m hearing both sides of this argument. And there are times when if that patient has been a long-termer and has very quiet disease, I might do it, whereas that patient says, “I might not.”

Alan P. Venook, MD: If you think about it as the patient, the patient is saying, “If it isn’t broke, don’t fix it.” And I do think that as we get older and perhaps we have our own infirmities, or we deal with these things, you realize that there’s a logic to that. I do think patients having some say or feeling like that. I think that’s important, within reason.

Transcript Edited for Clarity

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Transcript:

John Marshall, MD:
Johanna, I’m going to ask you to start about managing the trifluridine/tipiracil, or TAS-102. The schedule, the dose, it’s a little complicated, and the side effects. How are you doing it?

Johanna Bendell, MD: So, we talked about oral treatments. I think one of the biggest things I talk to my patients about is just because these are pills, doesn’t mean that they can’t be dangerous. I think a lot of patients think, “Oh, I’m taking a pill.” They think it’s like a multivitamin, so I’ve seen people miss a dose a lot. And so, there’s a lot of education that goes when you’re trusting the patient to take these certain pills. One of the things that I try to do for my TAS-102 patients is I say, “Monday through Friday, Monday through Friday, 2 weeks off.” Because I think it’s easier for them to remember Monday through Friday than trying to count out 5 days and 2 days. For some patients, they want to start on a different day and I say, “Mark it on your calendar.” So, we talk a lot about treatment calendars. What we see with TAS-102, and as Tony alluded to, is mostly neutropenia as the biggest side effect. And, in fact, there have been data published that suggest that the more neutropenia that you have or treatment delays due to neutropenia, the better you’re going to do on the TAS-102, which is ironic. That doesn’t say take more. But what I do is often times—and I think for a good chunk of the patients, maybe 20% to 25%—I end up delaying it. It becomes, instead of a 4-week cycle, a 5-week cycle. So, I tend to just give them a little extra time off rather than dose-reduce and try to keep them more at full dose.

John Marshall, MD: I don’t use a lot of growth factor in my practice. Is this a place you think about it?

Johanna Bendell, MD: Yes, I’ve seen people do it. The timing is right to do it. Have I done it before? A couple of times where people really fell low and it was more than a 1-week delay.

John Marshall, MD: And then, do you do anything funky with the 2 pills sizes? Now that you’ve got this 5-day on, 2-day off schedule and 2 pill sizes, what do you do?

Johanna Bendell, MD: I never use both pill sizes, I round. I do the same thing with capecitabine. I think it’s too confusing for patients to figure out, “How many of these pills do I take versus how many of those pills do I take?”

John Marshall, MD: You guys are going to get mad at me, but I tend to believe VEGF inhibition is a good thing. And when I give this drug, I try to keep the bevacizumab going. Anybody else with me?

Alan P. Venook, MD: Well, of course, if you’re using regorafenib, you probably are continuing the anti-VEGF. I’ve actually evolved to believe that as well. I do think, in many patients, there’s an apparent rebound from the discontinuation of bevacizumab. We see that after all in the TML study, which there was not a huge difference in outcome, but clearly in earlier line. And so, I actually do agree with you. I think the truth is that many folks in the community do it, and I’ve come to believe that, in fact, it may be a difference maker for some patients.

John Marshall, MD: And, of course, we’re going to get more data, right? These drugs are moving earlier, combinations are being done.

Tanios Bekaii-Saab, MD: Well, I think that we do have earlier data with 5-FU and bevacizumab in third-line, which essentially seem to add very little benefit or not.

John Marshall, MD: But, to be fair, it’s not randomized discontinuation, so it’s not against a placebo.

Tanios Bekaii-Saab, MD: Understood, but when I look at even bevacizumab beyond progression when you get to second-line, you lose significant benefit already. So, I’m not sure that I would venture down that way with minimal data. I can’t say that it’s wrong. I just think that I wouldn’t use it in clinic before I see more convincing data.

John Marshall, MD: Every time I think about it and do it, I’m hearing both sides of this argument. And there are times when if that patient has been a long-termer and has very quiet disease, I might do it, whereas that patient says, “I might not.”

Alan P. Venook, MD: If you think about it as the patient, the patient is saying, “If it isn’t broke, don’t fix it.” And I do think that as we get older and perhaps we have our own infirmities, or we deal with these things, you realize that there’s a logic to that. I do think patients having some say or feeling like that. I think that’s important, within reason.

Transcript Edited for Clarity
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