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Next-Generation Sequencing for Metastatic CRC

Panelists: John L. Marshall, MD, Georgetown University; Bert H. ONeil, MD, Indiana University School of Medicine; Marwan Fakih, MD, City of Hope Comprehensive Care Center; Gabriela Chiorean, MD, University of Washington School of Medicine; Wells A. Messersmith, MD, FACP, University of Colorado Cancer Center
Published: Thursday, Aug 30, 2018



Transcript: 

John L. Marshall, MD: All right, gang, you’re amazing. Let’s shift gears from sort of adjuvant therapy in rectal cancer to metastatic disease. A lot of stuff going on here. Clearly, colon cancer is more than one disease right now, anatomically and molecularly. Bert, how and when do I do molecular testing? I would never, ever, ever take care of a breast cancer patient without knowing HER2 [human epidermal growth factor receptor 2), ER [estrogen receptor], PR [progesterone receptor], and the like. And yet I see lots and lots of patients with colon cancer with 0 molecular testing when we start out. What’s the right answer to when and what do you send?

Bert H. O’Neil, MD: Well, I think off the bat you should ideally have their RAS status, KRAS and NRAS. You should probably know their RAF status up front, BRAF. We should definitely know their MSI [microsatellite instable] status. Tougher question is, should you order a bigger panel than that early on versus waiting until later? It’s interesting. For us, our own pathology department was running sort of a small colon panel for a while. They’ve shifted gears recently and told us go ahead and just send these to Foundation. So now I don’t even have a choice. I’m getting more than the information I just mentioned right off the bat.

John L. Marshall, MD: Some of the next-generation panels give you MSI maybe better than that, and you get some TML and some other things. I think there’s clearly a shift toward broad panels. But let me ask the hard question, Marwan. Do you start therapy? That patient wants treatment, right? And often the only biopsy you got is a little alligator snip from the colon primary with maybe not a biopsy of the metastases, right? And that’s going to take what, 10 to 14 days for that result to come back? Do you wait, or do you start?

Marwan Fakih, MD: I start. Let’s face it, there’s zero evidence that lack of 2 cycles of targeted therapies does anything bad to a patient, right? So patients are anxious, you want to start, you want to attack the cancer, and they have extensive disease. I think starting with FOLFOX, FOLFIRI if you prefer, or for some, FOLFOXIRI in some instances may not be an unreasonable approach while waiting for the next-generation sequencing data. And that’s what we do in our practice.

John L. Marshall, MD: I’ve got right now a patient who’s 34 years old with a tight sigmoid lesion and a liver full of tumors, symptomatic. Her profile is cooking. I happen to know she’s microsatellite stable. What should I give her while I’m waiting on my RAS to come back?

Gabriela Chiorean, MD: First of all, how tight is that sigmoid?

John L. Marshall, MD: Tight. She was needing significant laxatives to move.

Gabriela Chiorean, MD: Because I think that really the emergent situation is, do we need to put a stent in that sigmoid to keep it open?

John L. Marshall, MD: I hate stents. I don’t want to put a stent.

Gabriela Chiorean, MD: So, I think start chemotherapy right away.

John L. Marshall, MD: Which drug? What should I use?

Gabriela Chiorean, MD: This is a left-sided tumor?

John L. Marshall, MD: Left-sided. I don’t know her RAS or BRAF yet.

Gabriela Chiorean, MD: You don’t know her RAS.

John L. Marshall, MD: I will in 4 days.

Gabriela Chiorean, MD: You will in 4 days. So I think start with chemotherapy, such as either FOLFOX or FOLFIRI, depending on if she is concerned about neuropathy or not or other GI toxicities. I think either one of the regimens is an acceptable way. And consider potentially adding an EGFR-targeted agent if your RAS comes back wild type.

Transcript Edited for Clarity 

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Transcript: 

John L. Marshall, MD: All right, gang, you’re amazing. Let’s shift gears from sort of adjuvant therapy in rectal cancer to metastatic disease. A lot of stuff going on here. Clearly, colon cancer is more than one disease right now, anatomically and molecularly. Bert, how and when do I do molecular testing? I would never, ever, ever take care of a breast cancer patient without knowing HER2 [human epidermal growth factor receptor 2), ER [estrogen receptor], PR [progesterone receptor], and the like. And yet I see lots and lots of patients with colon cancer with 0 molecular testing when we start out. What’s the right answer to when and what do you send?

Bert H. O’Neil, MD: Well, I think off the bat you should ideally have their RAS status, KRAS and NRAS. You should probably know their RAF status up front, BRAF. We should definitely know their MSI [microsatellite instable] status. Tougher question is, should you order a bigger panel than that early on versus waiting until later? It’s interesting. For us, our own pathology department was running sort of a small colon panel for a while. They’ve shifted gears recently and told us go ahead and just send these to Foundation. So now I don’t even have a choice. I’m getting more than the information I just mentioned right off the bat.

John L. Marshall, MD: Some of the next-generation panels give you MSI maybe better than that, and you get some TML and some other things. I think there’s clearly a shift toward broad panels. But let me ask the hard question, Marwan. Do you start therapy? That patient wants treatment, right? And often the only biopsy you got is a little alligator snip from the colon primary with maybe not a biopsy of the metastases, right? And that’s going to take what, 10 to 14 days for that result to come back? Do you wait, or do you start?

Marwan Fakih, MD: I start. Let’s face it, there’s zero evidence that lack of 2 cycles of targeted therapies does anything bad to a patient, right? So patients are anxious, you want to start, you want to attack the cancer, and they have extensive disease. I think starting with FOLFOX, FOLFIRI if you prefer, or for some, FOLFOXIRI in some instances may not be an unreasonable approach while waiting for the next-generation sequencing data. And that’s what we do in our practice.

John L. Marshall, MD: I’ve got right now a patient who’s 34 years old with a tight sigmoid lesion and a liver full of tumors, symptomatic. Her profile is cooking. I happen to know she’s microsatellite stable. What should I give her while I’m waiting on my RAS to come back?

Gabriela Chiorean, MD: First of all, how tight is that sigmoid?

John L. Marshall, MD: Tight. She was needing significant laxatives to move.

Gabriela Chiorean, MD: Because I think that really the emergent situation is, do we need to put a stent in that sigmoid to keep it open?

John L. Marshall, MD: I hate stents. I don’t want to put a stent.

Gabriela Chiorean, MD: So, I think start chemotherapy right away.

John L. Marshall, MD: Which drug? What should I use?

Gabriela Chiorean, MD: This is a left-sided tumor?

John L. Marshall, MD: Left-sided. I don’t know her RAS or BRAF yet.

Gabriela Chiorean, MD: You don’t know her RAS.

John L. Marshall, MD: I will in 4 days.

Gabriela Chiorean, MD: You will in 4 days. So I think start with chemotherapy, such as either FOLFOX or FOLFIRI, depending on if she is concerned about neuropathy or not or other GI toxicities. I think either one of the regimens is an acceptable way. And consider potentially adding an EGFR-targeted agent if your RAS comes back wild type.

Transcript Edited for Clarity 
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