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EGFR Therapy for Right-Sided CRC

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: Thursday, Feb 14, 2019



Transcript: 

John L. Marshall, MD:
Chris, is there ever a time when you’re going to use an EGFR therapy in a right-sided colon cancer?

Christopher Lieu, MD: Yeah. I think it’s very clear that in the front-line setting we should not be using EGFR inhibitors, regardless of the RAS subtype. So, RAS wild-type, RAS mutation, you don’t want to use it. And it’s amazing in this day and age of next-generation sequencing that the sidedness is actually more predictive than the genetic alterations.

Howard S. Hochster, MD, FACP: And it’s free.

Christopher Lieu, MD: That’s right. The part that we don’t know is what to do in the second-line setting, right? So, if you have a right-sided tumor that you’ve treated with FOLFOX/bevacizumab in a front-line setting, and they’re RAS wild-type, and they have a right-sided tumor, in the second-line setting, do you opt for an EGFR inhibitor in that setting? And I think that’s where the data starts to fall apart. We don’t have really great retrospective data a lot of times because the sidedness wasn’t collected in some of the trials that were done. We have some hints from small retrospective looks that it’s just truly a bad prognostic marker.

John L. Marshall, MD: What are you doing? Let’s make them third-line [therapy], and you’ve gone Bev [bevacizumab] beyond progression, for example, and now you’re third-line [therapy] in a patient who you’d like to try another line of therapy. Are you trying it?

Christopher Lieu, MD: Yeah. So, in this situation I think you have the leeway to do it, right? There isn’t data to suggest that you shouldn’t do it, and you want to give these patients every chance possible, and you know that the patients that are most likely to benefit are going to be RAS wild-type, and so I think in later lines it is something that you can use, but not in the frontline setting.

John L. Marshall, MD: Is anybody against what Chris is saying?

Tanios S. Bekaii-Saab, MD: Actually, to support what Chris said, a study with cetuximab versus best supportive care reported on the right verses left. Again, they had some missing data. But it was interesting to see that on the right-sided tumors, cetuximab versus best supportive care did not affect progression-free survival. But, there was a survival benefit. It was small, but there was a survival benefit. It should remain an option. I wouldn’t use it in the first line; frankly, I wouldn’t use it in the second line. But for third line and beyond, I think it’s reasonable to expose those patients to an EGFR inhibitor, whether it’s cetuximab or panitumumab.

John L. Marshall, MD: And personally, right now I’m not expecting the response. If I’ve got a left-sided RAS wild-type, BRAF wild-type tumor, I’m expecting a good card I’m going to play here. But in these right-sided ones, you know I haven’t really been, now that I’m looking, I’m not really seeing much of a response there. Do you have a difference of opinion?

Joleen M. Hubbard, MD: No, I completely agree. I think we try to maximize all the potential options that we have for patients. So, saving this as a third-line option for patients I think is very appropriate.

John L. Marshall, MD: Howard, why is this? Why are left-sided cancers better than right?

Howard S. Hochster, MD, FACP: Well, I think staying away from the politics of left versus right, the right-sided tumors clearly have a worse overall prognosis. And I kind of think it’s like a poor man’s molecular biology test. We don’t know what we’re looking at when we see that, but some of it’s due to more BRAF on the right side, some of it’s due to, like in the CMS [consensus molecular subtypes] classification, some of the poorer prognosis groups are more on the right side. So, I think if we really understood the molecular biology, we’d probably be able to account for all of the issues that make the prognosis worse. But, you know, it’s hard to beat that test for cost effectiveness. You know from the first CAT scan if it’s right side or left side, and even the surgeons can figure it out.

John L. Marshall, MD: Are patients aware of this, Joleen? Do they know that they’ve got a right-sided tumor and it’s bad or?

Joleen M. Hubbard, MD: Surprisingly patients don’t really talk about that. They talk about results of the IDEA trial and things like that, but they’re not saying, “Hey, I’ve got a left-sided tumor, aren’t you going to do this?” So, I’m not sure why the left versus right hasn’t made it into the patient advocacy space. But patients don’t really bring that up. I don’t know about anyone else’s experience?

John L. Marshall, MD: Maybe there’s not much we can do about it.

I mean, it limits maybe drug choices, but it’s sort of like beating them over the head and then, “Sorry, I can’t …”

Joleen M. Hubbard, MD: Yeah, exactly.

John L. Marshall, MD: But the same, because I haven’t really seen a lot of patient awareness.


Transcript Edited for Clarity
 

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Transcript: 

John L. Marshall, MD:
Chris, is there ever a time when you’re going to use an EGFR therapy in a right-sided colon cancer?

Christopher Lieu, MD: Yeah. I think it’s very clear that in the front-line setting we should not be using EGFR inhibitors, regardless of the RAS subtype. So, RAS wild-type, RAS mutation, you don’t want to use it. And it’s amazing in this day and age of next-generation sequencing that the sidedness is actually more predictive than the genetic alterations.

Howard S. Hochster, MD, FACP: And it’s free.

Christopher Lieu, MD: That’s right. The part that we don’t know is what to do in the second-line setting, right? So, if you have a right-sided tumor that you’ve treated with FOLFOX/bevacizumab in a front-line setting, and they’re RAS wild-type, and they have a right-sided tumor, in the second-line setting, do you opt for an EGFR inhibitor in that setting? And I think that’s where the data starts to fall apart. We don’t have really great retrospective data a lot of times because the sidedness wasn’t collected in some of the trials that were done. We have some hints from small retrospective looks that it’s just truly a bad prognostic marker.

John L. Marshall, MD: What are you doing? Let’s make them third-line [therapy], and you’ve gone Bev [bevacizumab] beyond progression, for example, and now you’re third-line [therapy] in a patient who you’d like to try another line of therapy. Are you trying it?

Christopher Lieu, MD: Yeah. So, in this situation I think you have the leeway to do it, right? There isn’t data to suggest that you shouldn’t do it, and you want to give these patients every chance possible, and you know that the patients that are most likely to benefit are going to be RAS wild-type, and so I think in later lines it is something that you can use, but not in the frontline setting.

John L. Marshall, MD: Is anybody against what Chris is saying?

Tanios S. Bekaii-Saab, MD: Actually, to support what Chris said, a study with cetuximab versus best supportive care reported on the right verses left. Again, they had some missing data. But it was interesting to see that on the right-sided tumors, cetuximab versus best supportive care did not affect progression-free survival. But, there was a survival benefit. It was small, but there was a survival benefit. It should remain an option. I wouldn’t use it in the first line; frankly, I wouldn’t use it in the second line. But for third line and beyond, I think it’s reasonable to expose those patients to an EGFR inhibitor, whether it’s cetuximab or panitumumab.

John L. Marshall, MD: And personally, right now I’m not expecting the response. If I’ve got a left-sided RAS wild-type, BRAF wild-type tumor, I’m expecting a good card I’m going to play here. But in these right-sided ones, you know I haven’t really been, now that I’m looking, I’m not really seeing much of a response there. Do you have a difference of opinion?

Joleen M. Hubbard, MD: No, I completely agree. I think we try to maximize all the potential options that we have for patients. So, saving this as a third-line option for patients I think is very appropriate.

John L. Marshall, MD: Howard, why is this? Why are left-sided cancers better than right?

Howard S. Hochster, MD, FACP: Well, I think staying away from the politics of left versus right, the right-sided tumors clearly have a worse overall prognosis. And I kind of think it’s like a poor man’s molecular biology test. We don’t know what we’re looking at when we see that, but some of it’s due to more BRAF on the right side, some of it’s due to, like in the CMS [consensus molecular subtypes] classification, some of the poorer prognosis groups are more on the right side. So, I think if we really understood the molecular biology, we’d probably be able to account for all of the issues that make the prognosis worse. But, you know, it’s hard to beat that test for cost effectiveness. You know from the first CAT scan if it’s right side or left side, and even the surgeons can figure it out.

John L. Marshall, MD: Are patients aware of this, Joleen? Do they know that they’ve got a right-sided tumor and it’s bad or?

Joleen M. Hubbard, MD: Surprisingly patients don’t really talk about that. They talk about results of the IDEA trial and things like that, but they’re not saying, “Hey, I’ve got a left-sided tumor, aren’t you going to do this?” So, I’m not sure why the left versus right hasn’t made it into the patient advocacy space. But patients don’t really bring that up. I don’t know about anyone else’s experience?

John L. Marshall, MD: Maybe there’s not much we can do about it.

I mean, it limits maybe drug choices, but it’s sort of like beating them over the head and then, “Sorry, I can’t …”

Joleen M. Hubbard, MD: Yeah, exactly.

John L. Marshall, MD: But the same, because I haven’t really seen a lot of patient awareness.


Transcript Edited for Clarity
 
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