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Puzzling Together the Pieces in mCRC

Insights From: John L. Marshall, MD, MedStar Georgetown University Hospital; Tanios S. Bekaii-Saab, MD, Mayo Clinic
Published: Friday, Apr 05, 2019



Transcript: 

John L. Marshall, MD:
So paint for us a couple of distinctive patients, where 1 you might go with sort of reintensification and one where you might be a little kinder, gentler.

Tanios S. Bekaii-Saab, MD: So we think about our patients, there are multiple elements as you said to me. All of us are so excited about molecular and genetic stuff. Now if you ask an oncologist who takes care of colorectal cancer, “How do you think about your patient?” They will recite you know the RASes and the HER2s and all this. That’s only 1 piece of the puzzle. Age … sidedness, response to prior therapy, tolerance.

John L. Marshall, MD: Location of METs [metastases]?

Tanios S. Bekaii-Saab, MD: Location of METs, tolerance to other therapy, patient’s preferences, etcetera. So I think there’s a lot of important factors that go in. You know, an 82-year-old patient that comes to my clinic first-line, usually it’s capecitabine and bevacizumab. I don’t feel like I have to go to FOLFOX [folinic acid/fluorouracil/oxaliplatin], and certainly FOLFIRI [folinic acid/fluorouracil/irinotecan] may be rough on those patients, and definitely not FOLFOXIRI [folinic acid/fluorouracil/oxaliplatin/irinotecan]. But, before I even do that I run the slew of genetic testing. Because if they have a HER2, I do a dual HER2. If they have an MSI [microsatellite instability]-high, PD-1 [programmed cell death protein 1] inhibitor.

John L. Marshall, MD: Right for the first line.

Tanios S. Bekaii-Saab, MD: Absolutely. I wouldn’t even care for chemotherapy, and some of these patients will never need or will never see chemotherapy. Some of the MSI-high, if you put them on that....

John L. Marshall, MD: Cause we’ll kill them with something else first, or?

Tanios S. Bekaii-Saab, MD: Because you have some really beautiful responses that; I mean for years now I’ve followed patients who have never even needed chemotherapy. It’s amazing. And then we have the NTRK fusions and all this. For a younger patient, let’s say your 45 year old coming through; you know, very symptomatic, left-sided tumor, all the good stuff,  we’ll go with FOLFOXIRI/bevacizumab. Then we go on capecitabine/bevacizumab, and 9 months down the line the patient progresses back. If there is no neuropathy, very low neuropathy, I probably will reinitiate FOLFOXIRI. On the other hand, if that patient progressed within 2 to 3 months on maintenance, then I would shift to an EGFR inhibitor.

John L. Marshall, MD: And they’re in trouble too, that patient.

Tanios S. Bekaii-Saab, MD: Yes, so maximum response to first-line therapy that includes, by the way, the duration of response. That also includes the time spent on the maintenance therapy, and when they essentially progressed goes into the equation about decisions regarding biologics or switch of chemotherapeutics, or reintroduction and reintensification.

John L. Marshall, MD: You know I’m probably bending a rule here a little bit or sort of bending the data in my favor. That patient with liver dominant disease who doesn’t have a gangbuster initial response. So some response, but a lot of liver disease on frontline therapy, maybe progressing back in the 9-month range, that’s a patient that I’m actually thinking about early liver-directed therapy. And the data’s soft here. We didn’t have a survival benefit in an overall study, but it’s not the same setting. Now when I think about how many tools I have left and that patient’s quality of life and the impact that Y90 [yttrium-90] can have, or some sort of liver-directed therapy, I’m partnering with our IR [interventional radiologist] guys, and I see that falling off, less doing that. So I [was] kind of hanging on when it was quite popular a while ago, less popular now. You’re in the less popular, or are you still using it on occasion in the right window?

Tanios S. Bekaii-Saab, MD: I’ve never really gone on the bandwagon all gung ho, but at the same time I’ve used it in select patients. So, for example, the scenario you just talked about, I think that’s an appropriate patient. You know, doing it in the right setting. I remember 1 of my patients who had essentially 3 liver spots, so liver dominant disease, but they were very few. Got through chemotherapy. Hated chemotherapy, just absolutely hated chemotherapy. Had a good response and 1 was a candidate, but they’re unresectable.

We actually talked to her about liver-directed therapy, and she essentially ended up on SIRT [selective internal radiation therapy]. Two years after she was still in remission. Now the biology for disease was favorable. Or what I did is I gave her modality that helped control disease. The rule of thumb is, if they’re chemosensitive, they’re radiosensitive. So this is relatively chemosensitive, and she ended up having further response with the SIRT, and ultimately didn’t need chemotherapy. And at this point she’s still chemotherapy-free.

So there is a role, whether it’s in the relative maintenance setting for the very few patients that may have a truly very well controlled liver disease. They still use it sometimes in the more refractory setting, although I haven’t really seen any significant outcomes when you go more refractory, regardless if the disease is still in the liver. So I’d say I’m somewhat in the middle road.

John L. Marshall, MD: It’s not crazy but it passes your mind.


Transcript Edited for Clarity
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Transcript: 

John L. Marshall, MD:
So paint for us a couple of distinctive patients, where 1 you might go with sort of reintensification and one where you might be a little kinder, gentler.

Tanios S. Bekaii-Saab, MD: So we think about our patients, there are multiple elements as you said to me. All of us are so excited about molecular and genetic stuff. Now if you ask an oncologist who takes care of colorectal cancer, “How do you think about your patient?” They will recite you know the RASes and the HER2s and all this. That’s only 1 piece of the puzzle. Age … sidedness, response to prior therapy, tolerance.

John L. Marshall, MD: Location of METs [metastases]?

Tanios S. Bekaii-Saab, MD: Location of METs, tolerance to other therapy, patient’s preferences, etcetera. So I think there’s a lot of important factors that go in. You know, an 82-year-old patient that comes to my clinic first-line, usually it’s capecitabine and bevacizumab. I don’t feel like I have to go to FOLFOX [folinic acid/fluorouracil/oxaliplatin], and certainly FOLFIRI [folinic acid/fluorouracil/irinotecan] may be rough on those patients, and definitely not FOLFOXIRI [folinic acid/fluorouracil/oxaliplatin/irinotecan]. But, before I even do that I run the slew of genetic testing. Because if they have a HER2, I do a dual HER2. If they have an MSI [microsatellite instability]-high, PD-1 [programmed cell death protein 1] inhibitor.

John L. Marshall, MD: Right for the first line.

Tanios S. Bekaii-Saab, MD: Absolutely. I wouldn’t even care for chemotherapy, and some of these patients will never need or will never see chemotherapy. Some of the MSI-high, if you put them on that....

John L. Marshall, MD: Cause we’ll kill them with something else first, or?

Tanios S. Bekaii-Saab, MD: Because you have some really beautiful responses that; I mean for years now I’ve followed patients who have never even needed chemotherapy. It’s amazing. And then we have the NTRK fusions and all this. For a younger patient, let’s say your 45 year old coming through; you know, very symptomatic, left-sided tumor, all the good stuff,  we’ll go with FOLFOXIRI/bevacizumab. Then we go on capecitabine/bevacizumab, and 9 months down the line the patient progresses back. If there is no neuropathy, very low neuropathy, I probably will reinitiate FOLFOXIRI. On the other hand, if that patient progressed within 2 to 3 months on maintenance, then I would shift to an EGFR inhibitor.

John L. Marshall, MD: And they’re in trouble too, that patient.

Tanios S. Bekaii-Saab, MD: Yes, so maximum response to first-line therapy that includes, by the way, the duration of response. That also includes the time spent on the maintenance therapy, and when they essentially progressed goes into the equation about decisions regarding biologics or switch of chemotherapeutics, or reintroduction and reintensification.

John L. Marshall, MD: You know I’m probably bending a rule here a little bit or sort of bending the data in my favor. That patient with liver dominant disease who doesn’t have a gangbuster initial response. So some response, but a lot of liver disease on frontline therapy, maybe progressing back in the 9-month range, that’s a patient that I’m actually thinking about early liver-directed therapy. And the data’s soft here. We didn’t have a survival benefit in an overall study, but it’s not the same setting. Now when I think about how many tools I have left and that patient’s quality of life and the impact that Y90 [yttrium-90] can have, or some sort of liver-directed therapy, I’m partnering with our IR [interventional radiologist] guys, and I see that falling off, less doing that. So I [was] kind of hanging on when it was quite popular a while ago, less popular now. You’re in the less popular, or are you still using it on occasion in the right window?

Tanios S. Bekaii-Saab, MD: I’ve never really gone on the bandwagon all gung ho, but at the same time I’ve used it in select patients. So, for example, the scenario you just talked about, I think that’s an appropriate patient. You know, doing it in the right setting. I remember 1 of my patients who had essentially 3 liver spots, so liver dominant disease, but they were very few. Got through chemotherapy. Hated chemotherapy, just absolutely hated chemotherapy. Had a good response and 1 was a candidate, but they’re unresectable.

We actually talked to her about liver-directed therapy, and she essentially ended up on SIRT [selective internal radiation therapy]. Two years after she was still in remission. Now the biology for disease was favorable. Or what I did is I gave her modality that helped control disease. The rule of thumb is, if they’re chemosensitive, they’re radiosensitive. So this is relatively chemosensitive, and she ended up having further response with the SIRT, and ultimately didn’t need chemotherapy. And at this point she’s still chemotherapy-free.

So there is a role, whether it’s in the relative maintenance setting for the very few patients that may have a truly very well controlled liver disease. They still use it sometimes in the more refractory setting, although I haven’t really seen any significant outcomes when you go more refractory, regardless if the disease is still in the liver. So I’d say I’m somewhat in the middle road.

John L. Marshall, MD: It’s not crazy but it passes your mind.


Transcript Edited for Clarity
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