Search Videos by Topic or Participant
Browse by Series:

Second-Line Therapy Options in mCRC

Panelists:Tanios Bekaii-Saab, MD, Ohio State University – James Cancer Hospital; Johanna Bendell, MD, Sarah Cannon Research Institute; Charles S. Fuchs, MD, Dana-Farber Cancer Institute; Richard Kim, MD, Moffitt Cancer Center; John L. Marshall, MD, Georgetown University Hospital
Published: Friday, Apr 22, 2016


Transcript:

John L. Marshall, MD:
Let’s shift gears. Second-line. I want to do this quickly. We have 3 VEGF inhibitors approved in second-line. We actually don’t have any EGFR inhibitors approved in second-line. We have guidelines on them on second-line. What’s your various approaches? Richard, I’ll start again with you. Use of biologics, and I’ll make it a RAS wild-type patient in second-line?

Richard Kim, MD: It has to be individualized, and not everybody in second-line will get EGFR or bevacizumab. There’s data to support using antiangiogenic agents beyond progression. There’s some data using EGFR even though there is no OS data on it. It really depends on the patient, how they progress after first-line. For example, if they’re KRAS wild-type and they progress within three to six months, which I call a rapid progressor, then I will change the backbone, I will change the biologic. However, if they’re on FOLFOX or 5-FU/bevacizumab for two to three years because [of] toxicity associated with EGFR, I will just continue bevacizumab and just change the backbone.

John L. Marshall, MD: And everybody pretty much agrees with that summary?

Tanios Bekaii-Saab, MD: No, it’s a reasonable approach. But I’ll be frank with you: since most patients actually respond and have a durable response, that’s what most patients in the first-line do. I go with FOLFIRI/bevacizumab, and at progression, if they’re RAS wild-type, I switch the biologic and keep the chemotherapy backbone the same. And it’s not better, but I just find it simpler to continue with the same chemotherapy backbone, flip the biologics, and leave FOLFOX to third-line.

John L. Marshall, MD: Yeah. There’s more and more evidence for an EGFR beyond progression and re-challenging, but it’s not really been a big US effort. We’ve been more second, more third-line with EGFR.

Charles S. Fuchs, MD: We have evidence that continuing bevacizumab into second-line improves survival. And we don’t really know that giving EGFR antibody sooner improves outcome.

John L. Marshall, MD: And who would have ever thought that bevacizumab would be the bargain among the VEGF inhibitors? We have aflibercept, we have ramucirumab. They’re approved in this setting. Is anybody using those routinely? I still see a lot of folks in community using those as single agents in the refractory setting because they get them approved. Would anybody support that as an approach?

Richard Kim, MD: Only reason why I would change the biologic, in terms of a different VEGF, would be, once again, same scenario where you give FOLFOX/bevacizumab, they progress rapidly after 3 months, and they’re KRAS-mutant. Then I may change the VEGF inhibitor, knowing that the mechanism is a little bit different. There’s no data to support this, but just a caveat to say if it didn’t work—FOLFOX/bevacizumab first-line—it’s a very poor prognosis.

Tanios Bekaii-Saab, MD: But that’s your 5%, 5% less of your patients will ever face this scenario. And those technically do worse anyway.

Richard Kim, MD: I agree.

Charles S. Fuchs, MD: Do you ever get any mileage from switching the VEGF inhibitor?

Richard Kim, MD: There’s no data, yeah.

John L. Marshall, MD: The more and more we’re doing biopsies and molecular profiles, the more changes in RAS status, both directions actually. Like in breast cancer, they routinely repeat biopsy around HER2. Should we be doing that in colorectal cancer?

Johanna Bendell, MD: I’ve been repeating biopsies as patients go down the line of therapies, and the question is, is it the same lesion you biopsy? Has the tumor itself actually changed? And this is where the liquid biopsy question comes in—though I don’t know, even though we have commercial assays available, that it’s ready to make decisions on. But, certainly, the more progressed patients get, we’ll check the tumor again.

John L. Marshall, MD: If I have a RAS wild-type in the bank, should I repeat biopsy or can I go?

Charles S. Fuchs, MD: I don’t think there’s any evidence that you actually have to change it, realizing that what we do know is that patients who got an EGFR antibody who become resistant will have evidence of a RAS mutation where they didn’t previously. But that’s different than your patient because you’re talking about a patient who hasn’t gotten EGFR antibody yet.

Transcript Edited for Clarity
Slider Left
Slider Right


Transcript:

John L. Marshall, MD:
Let’s shift gears. Second-line. I want to do this quickly. We have 3 VEGF inhibitors approved in second-line. We actually don’t have any EGFR inhibitors approved in second-line. We have guidelines on them on second-line. What’s your various approaches? Richard, I’ll start again with you. Use of biologics, and I’ll make it a RAS wild-type patient in second-line?

Richard Kim, MD: It has to be individualized, and not everybody in second-line will get EGFR or bevacizumab. There’s data to support using antiangiogenic agents beyond progression. There’s some data using EGFR even though there is no OS data on it. It really depends on the patient, how they progress after first-line. For example, if they’re KRAS wild-type and they progress within three to six months, which I call a rapid progressor, then I will change the backbone, I will change the biologic. However, if they’re on FOLFOX or 5-FU/bevacizumab for two to three years because [of] toxicity associated with EGFR, I will just continue bevacizumab and just change the backbone.

John L. Marshall, MD: And everybody pretty much agrees with that summary?

Tanios Bekaii-Saab, MD: No, it’s a reasonable approach. But I’ll be frank with you: since most patients actually respond and have a durable response, that’s what most patients in the first-line do. I go with FOLFIRI/bevacizumab, and at progression, if they’re RAS wild-type, I switch the biologic and keep the chemotherapy backbone the same. And it’s not better, but I just find it simpler to continue with the same chemotherapy backbone, flip the biologics, and leave FOLFOX to third-line.

John L. Marshall, MD: Yeah. There’s more and more evidence for an EGFR beyond progression and re-challenging, but it’s not really been a big US effort. We’ve been more second, more third-line with EGFR.

Charles S. Fuchs, MD: We have evidence that continuing bevacizumab into second-line improves survival. And we don’t really know that giving EGFR antibody sooner improves outcome.

John L. Marshall, MD: And who would have ever thought that bevacizumab would be the bargain among the VEGF inhibitors? We have aflibercept, we have ramucirumab. They’re approved in this setting. Is anybody using those routinely? I still see a lot of folks in community using those as single agents in the refractory setting because they get them approved. Would anybody support that as an approach?

Richard Kim, MD: Only reason why I would change the biologic, in terms of a different VEGF, would be, once again, same scenario where you give FOLFOX/bevacizumab, they progress rapidly after 3 months, and they’re KRAS-mutant. Then I may change the VEGF inhibitor, knowing that the mechanism is a little bit different. There’s no data to support this, but just a caveat to say if it didn’t work—FOLFOX/bevacizumab first-line—it’s a very poor prognosis.

Tanios Bekaii-Saab, MD: But that’s your 5%, 5% less of your patients will ever face this scenario. And those technically do worse anyway.

Richard Kim, MD: I agree.

Charles S. Fuchs, MD: Do you ever get any mileage from switching the VEGF inhibitor?

Richard Kim, MD: There’s no data, yeah.

John L. Marshall, MD: The more and more we’re doing biopsies and molecular profiles, the more changes in RAS status, both directions actually. Like in breast cancer, they routinely repeat biopsy around HER2. Should we be doing that in colorectal cancer?

Johanna Bendell, MD: I’ve been repeating biopsies as patients go down the line of therapies, and the question is, is it the same lesion you biopsy? Has the tumor itself actually changed? And this is where the liquid biopsy question comes in—though I don’t know, even though we have commercial assays available, that it’s ready to make decisions on. But, certainly, the more progressed patients get, we’ll check the tumor again.

John L. Marshall, MD: If I have a RAS wild-type in the bank, should I repeat biopsy or can I go?

Charles S. Fuchs, MD: I don’t think there’s any evidence that you actually have to change it, realizing that what we do know is that patients who got an EGFR antibody who become resistant will have evidence of a RAS mutation where they didn’t previously. But that’s different than your patient because you’re talking about a patient who hasn’t gotten EGFR antibody yet.

Transcript Edited for Clarity
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Working Group to Optimize Outcomes in EGFR-mutated Lung Cancers: Evolving Concepts for Nurses to Facilitate and Improve Patient CareJun 30, 20181.5
Oncology Briefings™: Overcoming Chronic Iron Overload in Pediatric AML and MDSJun 30, 20181.0
Publication Bottom Border
Border Publication
x