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Maintenance Strategies for Patients With mCRC

Panelists: Howard Hochster, MD, FACP, Rutgers Cancer Institute; Joleen Hubbard, MD, Mayo Clinic; Christopher Lieu, MD, University of Colorado School of Medicine; John Marshall, MD, Georgetown University Hospital; Tony Saab, MD, Mayo Clinic
Published: Friday, Feb 22, 2019



Transcript: 

John L. Marshall, MD:
Tony, let’s shift gears a little bit to after initial lines of therapy—this very important concept of maintenance therapy, which I think is increasingly embedded into our treatment algorithms but not everybody does it the same or not everybody’s embracing this thought. I’ll have to give the preamble that we really must get away from this concept that there’s something magical about 12 cycles of chemotherapy. So, what’s your approach to maintenance with some of the supporting evidence? And we’ll get other folks to chime in on that.

Tanios S. Bekaii-Saab, MD: You know for the longest time we’ve been asking these questions. And primarily this was driven by the cumulative toxicities, from oxaliplatin, although the discussion applies to FOLFIRI or FOLFOX or what have you. It is interesting to see that through a lot of the studies that have been done, frankly the maximal response you obtain from any regimen is in the first 3 to 4 months. Beyond 3 to 4 months you’re probably exposing patients primarily to the toxicities of the regimen when foregoing some of the added benefits.

So, the first questions were, can we give the patients maintenance versus continuous therapy? And it sounds that you could give them maintenance and it sounds good, rather than just hammer them down. The next question was, can we give them a holiday versus continue the chemotherapy at a maintenance level? And it turns out that there’s probably a little advantage to do the maintenance level, primarily in delaying disease progression. The survival may be not as much affected. And then these were prior to the biologic areas. And then the CAIRO3, which I think establishes somewhat our standard and exposed patients to about 4-months, so about 16 weeks of chemotherapy, then went to capecitabine and bevacizumab—a low-dose capecitabine continuous, which is more merciful. And it actually did show, for its primary endpoint, which was primarily delaying disease progression, that it was positive.

Survival, again, was slightly improved, but there are many factors that affect that. So, in many ways, today when we think about our patients that come to the clinic, we’re thinking about a marathon. We’re not thinking about a sprint anymore. I mean these are patients that are living 3, 4, 5 years. Some of them are living for 10 years. So, what you do first is going to affect or set the tone for the rest of their lifetime on treatment. So, I think it is obligatory. I don’t think it’s an option any more. Every patient with colon cancer gets treated with 3, 4 months of what I call induction therapy, to borrow from our hematologic oncology colleagues, and then they go on maintenance. And frankly, for some patients, a holiday is okay.

John L. Marshall, MD:  Yeah, I sometimes wonder if our language maintenance was a bad choice. To me it’s sort of de-intensifying.

Tanios S. Bekaii-Saab, MD: De-intensifying.

John L. Marshall, MD: It’s like they’re dropping from 3 drugs to 2, or what not. Chris, I’ve been seeing all sorts of different strategies. I tend to be a capecitabine junky. I mean I take it pretty much twice a day and look at what it’s doing, it’s great. But you know I still see so many patients out there who are getting maintenance pump with their Bev [bevacizumab]. And I know, a lot of our community partners are like, “Well, I can’t really shift over to oral.” From a practical perspective, if the support that’s required for oral anticancer drugs is hard on practices, and so they’re sort of anti-capecitabine in some ways, what do you think about different approaches and how maintenance should be done?

Christopher Lieu, MD: Yeah, no, I would agree with you that I am also a capecitabine junky. And we really just framed this in terms of a discussion with the patient. “We want to de-intensify your treatment without any reduction in your survival benefit.” I think that’s an important thing because our patients are worried about that. “We’re doing this to preserve your quality of life.” I think that really resonates with patients. And just like Tony said, sometimes a treatment break is in a patient’s goals, right? Because that’s what we’re really trying to meet.

And then we also put this in the fame of, “Well, do you want to be hooked up to a pump for 4 to 6 hours every other week?” Or, “Do you want to take or try this? Do you want to take a pill twice a day?” We do treat patients that have very active lifestyles, and hopefully by this time they are doing well. And if we reduce chemotherapy, they’ll be even more active. And so, this idea of being connected to a pump is something that I think a lot of patients, if they have the option to, would choose not to do. And so, we do capecitabine and bevacizumab every 3 weeks. And then we do discuss a potential treatment break, which I’ve done in rare instances, where that lined up with our patients’ goals.

John L. Marshall, MD: Who is that patient that you’re offering a treatment break to?

Christopher Lieu, MD: So, it really depends on how they’re doing with chemotherapy. If they’re just absolutely miserable, and you know that even with the intensification of chemotherapy that the side effects are just going to be really, really poor, and, in addition, their disease is under good control, then that is something where you just have to have an honest conversation. “What is it that you really want to gain out of this treatment? Should we just try and get you to a lower dose of chemotherapy where quality of life is better, or are you just really done? And then we can continue to monitor you.” I think the data would always suggest that doing something is better than doing nothing, but that doesn’t necessarily mean it’s the right thing for every single patient.

John L. Marshall, MD: Is there somebody, Joleen, that you’d say, “No, you should stop.” Like their CEA goes from 100 to 2, and everything is now down to 3 mm and it’s hard to measure, but they’re not resectable. Is that a maintenance patient or is that a, “You should stop?”

Joleen M. Hubbard, MD: I do give the option to the patient. It is really patient preference. Some patients cannot handle the fact that they have cancer but they’re not on treatment. Mentally they just can’t get over that. And so, I really do leave it up to the patient. I present the data and say, “Look, we think that there’s definitely a progression-free survival benefit, but I can’t tell you with 100% certainty that there’s an overall survival benefit with this approach. And if you wanted to take a holiday, we certainly could. It wouldn’t necessarily be wrong.”

Howard S. Hochster, MD, FACP: I was going to say that I tend to continue on maintenance with CAPE [capecitabine]-Bev, and I’m not a CAPE junkie. I don’t really like capecitabine. I think it’s more toxic, more expensive, and the 14-day schedule is really not a good one. And it’s not taking a pill twice a day, it’s taking 2, 3, or 4 pills twice a day. So, it’s not my favorite drug. But I do use it in maintenance, and I think the low dose maintenance with the 3 weekly Bev is really very good for a patient’s quality of life.

What I tend to do is after induction I’ll go on maintenance for a while and then try them on observation or a treatment break to see how they do. There are clearly people that could go 6 to 12 months, and there are people that within 3 months you have to restart. And I wish I had a biomarker to tell, because you usually can’t tell except by just the test of time and repeating the CAT scan.

Tanios S. Bekaii-Saab, MD: I think there are 2 important things to keep in mind when you think about maintenance strategies. One, in my own clinic at least, and I realize capecitabine can be tough, we give it daily, but I do Monday to Friday, weekends off, consistently. The patients are able to understand Monday to Friday and weekends off. They don’t get confused.

John L. Marshall, MD: I’ve always said that if radiation doesn’t work on the weekends, neither does capecitabine.

Tanios S. Bekaii-Saab, MD: Yeah, neither does capecitabine. And I think that’s very important. The other very important point, that is very important to remind our colleagues, is that bevacizumab on its own should not be used for maintenance. It does not work. It does not help. If you want to maintain patients, it’s a fluoropyrimidine plus bevacizumab. Do not use the monoclonal antibody on its own.

Howard S. Hochster, MD, FACP: While I agree that 5 days of CAPE might be enough every 7 days, we don’t really have any good prospective data. Personally, if I were going to go to a less intense regimen in 14 days, at every 21 I’d tend to do a week on, a week off, because at least there are a couple of trials in that regard.

John L. Marshall, MD: We all have different recipes.


Transcript Edited for Clarity

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Transcript: 

John L. Marshall, MD:
Tony, let’s shift gears a little bit to after initial lines of therapy—this very important concept of maintenance therapy, which I think is increasingly embedded into our treatment algorithms but not everybody does it the same or not everybody’s embracing this thought. I’ll have to give the preamble that we really must get away from this concept that there’s something magical about 12 cycles of chemotherapy. So, what’s your approach to maintenance with some of the supporting evidence? And we’ll get other folks to chime in on that.

Tanios S. Bekaii-Saab, MD: You know for the longest time we’ve been asking these questions. And primarily this was driven by the cumulative toxicities, from oxaliplatin, although the discussion applies to FOLFIRI or FOLFOX or what have you. It is interesting to see that through a lot of the studies that have been done, frankly the maximal response you obtain from any regimen is in the first 3 to 4 months. Beyond 3 to 4 months you’re probably exposing patients primarily to the toxicities of the regimen when foregoing some of the added benefits.

So, the first questions were, can we give the patients maintenance versus continuous therapy? And it sounds that you could give them maintenance and it sounds good, rather than just hammer them down. The next question was, can we give them a holiday versus continue the chemotherapy at a maintenance level? And it turns out that there’s probably a little advantage to do the maintenance level, primarily in delaying disease progression. The survival may be not as much affected. And then these were prior to the biologic areas. And then the CAIRO3, which I think establishes somewhat our standard and exposed patients to about 4-months, so about 16 weeks of chemotherapy, then went to capecitabine and bevacizumab—a low-dose capecitabine continuous, which is more merciful. And it actually did show, for its primary endpoint, which was primarily delaying disease progression, that it was positive.

Survival, again, was slightly improved, but there are many factors that affect that. So, in many ways, today when we think about our patients that come to the clinic, we’re thinking about a marathon. We’re not thinking about a sprint anymore. I mean these are patients that are living 3, 4, 5 years. Some of them are living for 10 years. So, what you do first is going to affect or set the tone for the rest of their lifetime on treatment. So, I think it is obligatory. I don’t think it’s an option any more. Every patient with colon cancer gets treated with 3, 4 months of what I call induction therapy, to borrow from our hematologic oncology colleagues, and then they go on maintenance. And frankly, for some patients, a holiday is okay.

John L. Marshall, MD:  Yeah, I sometimes wonder if our language maintenance was a bad choice. To me it’s sort of de-intensifying.

Tanios S. Bekaii-Saab, MD: De-intensifying.

John L. Marshall, MD: It’s like they’re dropping from 3 drugs to 2, or what not. Chris, I’ve been seeing all sorts of different strategies. I tend to be a capecitabine junky. I mean I take it pretty much twice a day and look at what it’s doing, it’s great. But you know I still see so many patients out there who are getting maintenance pump with their Bev [bevacizumab]. And I know, a lot of our community partners are like, “Well, I can’t really shift over to oral.” From a practical perspective, if the support that’s required for oral anticancer drugs is hard on practices, and so they’re sort of anti-capecitabine in some ways, what do you think about different approaches and how maintenance should be done?

Christopher Lieu, MD: Yeah, no, I would agree with you that I am also a capecitabine junky. And we really just framed this in terms of a discussion with the patient. “We want to de-intensify your treatment without any reduction in your survival benefit.” I think that’s an important thing because our patients are worried about that. “We’re doing this to preserve your quality of life.” I think that really resonates with patients. And just like Tony said, sometimes a treatment break is in a patient’s goals, right? Because that’s what we’re really trying to meet.

And then we also put this in the fame of, “Well, do you want to be hooked up to a pump for 4 to 6 hours every other week?” Or, “Do you want to take or try this? Do you want to take a pill twice a day?” We do treat patients that have very active lifestyles, and hopefully by this time they are doing well. And if we reduce chemotherapy, they’ll be even more active. And so, this idea of being connected to a pump is something that I think a lot of patients, if they have the option to, would choose not to do. And so, we do capecitabine and bevacizumab every 3 weeks. And then we do discuss a potential treatment break, which I’ve done in rare instances, where that lined up with our patients’ goals.

John L. Marshall, MD: Who is that patient that you’re offering a treatment break to?

Christopher Lieu, MD: So, it really depends on how they’re doing with chemotherapy. If they’re just absolutely miserable, and you know that even with the intensification of chemotherapy that the side effects are just going to be really, really poor, and, in addition, their disease is under good control, then that is something where you just have to have an honest conversation. “What is it that you really want to gain out of this treatment? Should we just try and get you to a lower dose of chemotherapy where quality of life is better, or are you just really done? And then we can continue to monitor you.” I think the data would always suggest that doing something is better than doing nothing, but that doesn’t necessarily mean it’s the right thing for every single patient.

John L. Marshall, MD: Is there somebody, Joleen, that you’d say, “No, you should stop.” Like their CEA goes from 100 to 2, and everything is now down to 3 mm and it’s hard to measure, but they’re not resectable. Is that a maintenance patient or is that a, “You should stop?”

Joleen M. Hubbard, MD: I do give the option to the patient. It is really patient preference. Some patients cannot handle the fact that they have cancer but they’re not on treatment. Mentally they just can’t get over that. And so, I really do leave it up to the patient. I present the data and say, “Look, we think that there’s definitely a progression-free survival benefit, but I can’t tell you with 100% certainty that there’s an overall survival benefit with this approach. And if you wanted to take a holiday, we certainly could. It wouldn’t necessarily be wrong.”

Howard S. Hochster, MD, FACP: I was going to say that I tend to continue on maintenance with CAPE [capecitabine]-Bev, and I’m not a CAPE junkie. I don’t really like capecitabine. I think it’s more toxic, more expensive, and the 14-day schedule is really not a good one. And it’s not taking a pill twice a day, it’s taking 2, 3, or 4 pills twice a day. So, it’s not my favorite drug. But I do use it in maintenance, and I think the low dose maintenance with the 3 weekly Bev is really very good for a patient’s quality of life.

What I tend to do is after induction I’ll go on maintenance for a while and then try them on observation or a treatment break to see how they do. There are clearly people that could go 6 to 12 months, and there are people that within 3 months you have to restart. And I wish I had a biomarker to tell, because you usually can’t tell except by just the test of time and repeating the CAT scan.

Tanios S. Bekaii-Saab, MD: I think there are 2 important things to keep in mind when you think about maintenance strategies. One, in my own clinic at least, and I realize capecitabine can be tough, we give it daily, but I do Monday to Friday, weekends off, consistently. The patients are able to understand Monday to Friday and weekends off. They don’t get confused.

John L. Marshall, MD: I’ve always said that if radiation doesn’t work on the weekends, neither does capecitabine.

Tanios S. Bekaii-Saab, MD: Yeah, neither does capecitabine. And I think that’s very important. The other very important point, that is very important to remind our colleagues, is that bevacizumab on its own should not be used for maintenance. It does not work. It does not help. If you want to maintain patients, it’s a fluoropyrimidine plus bevacizumab. Do not use the monoclonal antibody on its own.

Howard S. Hochster, MD, FACP: While I agree that 5 days of CAPE might be enough every 7 days, we don’t really have any good prospective data. Personally, if I were going to go to a less intense regimen in 14 days, at every 21 I’d tend to do a week on, a week off, because at least there are a couple of trials in that regard.

John L. Marshall, MD: We all have different recipes.


Transcript Edited for Clarity
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