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ONCAlert | Upfront Therapy for mRCC

Case 3: TAS-102 Dose Adjustment in mCRC

Targeted Oncology
Published Online:1:34 PM, Wed November 21, 2018

Shubham Pant, MD: Richard, clinically when somebody is on TAS-102 [trifluridine/tipiracil], how often are you doing their counts? Neutropenia, as you know, was the big one. How often do you do the counts? Do you do any dose adjustments like you would do for regorafenib [Stivarga], but for different reasons?

Richard Kim, MD: Yes. There are some data for TAS-102 that demonstrates that it is dose dependent. It is a cytotoxic chemotherapy. Dose does matter. So there’s some trend, at least in the community, to start to underdose. This may be based on the experience with regorafenib. There’s clear data that [say] that dose does matter in TAS-102. The recommended dose is 35 mg/m2 BID [twice daily] on days 1 through 5. Per label, you’re supposed to see the patient back at day 15 to check their counts. I do see the patient back at day 15 to look at toxicity and to make sure the patient has no other toxicity, other than neutropenia, fatigue, or other problems.

However, there’s no correlation between day 15 counts and cycle 2/day 1 neutropenia. So we checked it. I don’t know what it really means, right? Therefore, when I see the patient back, at cycle 2/day 1, depending on their counts, we do have to dose delay. We sometimes have to dose delay if, for example, per the guidelines, they have a platelet count under 1000. If it’s below that, we have to delay for 1 week, then we start at the same dose. We do not dose reduce when the counts come up, but actually dose delay. There are certain indications that are recommended to dose reduce. For example, if you have febrile neutropenia, for example, you have to dose reduce.

Shubham Pant, MD: Thank you for that. Mike, is this the same in your practice?

Michael Morse, MD: Yes, absolutely. Richard emphasized the important point: It’s been observed, from the pivotal trial, that for most patients, if they have any alteration at all in the administration of the drug, it’s actually just a delay. About 50% of people ultimately needed a delay. A very small number of people needed a dose reduction. Almost nobody needed to stop the drug because of intolerance to it. It was mainly stopped for progression. I think it gives us comfort that you can keep people on the recommended dose and it will be tolerable for people, even if it requires a delay of 1 week before their next therapy.

Shubham Pant, MD: Thank you Greg, Mike, and Richard. This has been a great discussion. As take-home points, when patients present with metastatic colorectal cancer in the frontline setting, we need to at least do testing for extended KRAS and NRAS, BRAF, and microsatellite instability. Next-generation sequencing is dependent on the physician. What do you think about the clinical outcome of the patient? This can give us really good targets. One thing that we then talk about is HER2/neu. That’s a potential thing that should be tested for in these patients. About 2% to 2.5% of patients are HER2/neu-overamplified, and there are studies out there suggesting the use of targeted agents. So that’s very important. It’s physician dependent. You have to think about the performance status of the patient. Everything has to be taken into consideration.

For third-line therapy, you have to look at the clinical scenario that you are faced with and the different toxicities. Based on how your patient presents, you can either choose to use regorafenib or TAS-102. Depending on the unique toxicities, the dose adjustment is also unique with both of the oral drugs. It’s purely dependent on how your patient is doing. Thank you so much for that discussion.

Transcript edited for clarity.

Shubham Pant, MD: Richard, clinically when somebody is on TAS-102 [trifluridine/tipiracil], how often are you doing their counts? Neutropenia, as you know, was the big one. How often do you do the counts? Do you do any dose adjustments like you would do for regorafenib [Stivarga], but for different reasons?

Richard Kim, MD: Yes. There are some data for TAS-102 that demonstrates that it is dose dependent. It is a cytotoxic chemotherapy. Dose does matter. So there’s some trend, at least in the community, to start to underdose. This may be based on the experience with regorafenib. There’s clear data that [say] that dose does matter in TAS-102. The recommended dose is 35 mg/m2 BID [twice daily] on days 1 through 5. Per label, you’re supposed to see the patient back at day 15 to check their counts. I do see the patient back at day 15 to look at toxicity and to make sure the patient has no other toxicity, other than neutropenia, fatigue, or other problems.

However, there’s no correlation between day 15 counts and cycle 2/day 1 neutropenia. So we checked it. I don’t know what it really means, right? Therefore, when I see the patient back, at cycle 2/day 1, depending on their counts, we do have to dose delay. We sometimes have to dose delay if, for example, per the guidelines, they have a platelet count under 1000. If it’s below that, we have to delay for 1 week, then we start at the same dose. We do not dose reduce when the counts come up, but actually dose delay. There are certain indications that are recommended to dose reduce. For example, if you have febrile neutropenia, for example, you have to dose reduce.

Shubham Pant, MD: Thank you for that. Mike, is this the same in your practice?

Michael Morse, MD: Yes, absolutely. Richard emphasized the important point: It’s been observed, from the pivotal trial, that for most patients, if they have any alteration at all in the administration of the drug, it’s actually just a delay. About 50% of people ultimately needed a delay. A very small number of people needed a dose reduction. Almost nobody needed to stop the drug because of intolerance to it. It was mainly stopped for progression. I think it gives us comfort that you can keep people on the recommended dose and it will be tolerable for people, even if it requires a delay of 1 week before their next therapy.

Shubham Pant, MD: Thank you Greg, Mike, and Richard. This has been a great discussion. As take-home points, when patients present with metastatic colorectal cancer in the frontline setting, we need to at least do testing for extended KRAS and NRAS, BRAF, and microsatellite instability. Next-generation sequencing is dependent on the physician. What do you think about the clinical outcome of the patient? This can give us really good targets. One thing that we then talk about is HER2/neu. That’s a potential thing that should be tested for in these patients. About 2% to 2.5% of patients are HER2/neu-overamplified, and there are studies out there suggesting the use of targeted agents. So that’s very important. It’s physician dependent. You have to think about the performance status of the patient. Everything has to be taken into consideration.

For third-line therapy, you have to look at the clinical scenario that you are faced with and the different toxicities. Based on how your patient presents, you can either choose to use regorafenib or TAS-102. Depending on the unique toxicities, the dose adjustment is also unique with both of the oral drugs. It’s purely dependent on how your patient is doing. Thank you so much for that discussion.

Transcript edited for clarity.
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