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Treatment Options for First- and Second-Line Left-Sided CRC

Panelists: Johanna C. Bendell,MD, Sarah Cannon Research Institute; Dirk Arnold, MD, PhD, KTB Klinik fur Tumorbiologie GmbH & Co. KG ; Heinz-Josef Lenz, MD, FACP, USC Center for Molecular Pathway and Drug Discovery; Zev A. Wainberg, MD, UCLA Medical Center
Published: Friday, Dec 14, 2018



Transcript: 

Johanna C. Bendell, MD:
So, now turning to the other 85% of the population, we talked about a lot of these rare patients. So I love asking this question of Dirk first, because you have been put on the hot seat—no pun intended—many times to speak about this. You have a left-sided RAS wild-type patient, first-line therapy. What’s your go-to?

Dirk Arnold, MD, PhD: Well, that’s a clear indication for an anti-EGF receptor antibody. So from a European perspective, it’s a no-brainer that these patients should be treated with an anti-EGFR in combination with a doublet chemotherapy.

Heinz-Josef Lenz, MD, FACP: You tell him.

Dirk Arnold, MD, PhD: I tell him.

Johanna C. Bendell, MD: Do you purposely choose an irinotecan-based treatment over an oxaliplatin-based treatment?

Dirk Arnold, MD, PhD: Depends. I think it’s still open. I think it’s a bit about handling management of toxicity, etc. Since there is some overlap in toxicity with the skin toxicity and neuropathy with oxaliplatin, some feel more familiar to use them or feel safer to use them with an irinotecan-based chemotherapy, but it works either way.

Johanna C. Bendell, MD: OK. Zev, you live in LA [Los Angeles], where the beautiful people are. What would your choice be for treating a first-line left-sided RAS wild-type patient?

Zev A. Wainberg, MD: So, I used to use much more bevacizumab [Avastin], obviously, but I actually started to use more EGFR inhibitors in that kind of patient too. I find the data compelling. I find it reproducible, and I’m not going to say every patient is necessarily starting on an EGFR. But definitely, my own personal use of an EGFR inhibitor has gone up dramatically in the frontline setting in left-sided tumors over the last few years.

Johanna C. Bendell, MD: Now, do you get any pushback from your patients about the rash?

Zev A. Wainberg, MD: We do. We get pushback. But the rash now I find easier to deal with than it has ever been with prophylactic antibiotics and with aggressive skin management. Actually, many times I find the rash to be less of a problem than just the dryness of the skin. The rash itself is OK when they’re on antibiotics. It’s the dryness of the skin that is somewhat cumulative, which is a struggle, particularly in Southern California. But nonetheless, you have enough data now to suggest a survival advantage in some of these cohorts. So I think that has compelled a lot of people to move more in that direction.

Johanna C. Bendell, MD: Now then, what do you do for second line. Do you ever bring bevacizumab in?

Zev A. Wainberg, MD: Bevacizumab in second line, yes. I mean, I still think that there’s a role for bevacizumab in second line, even in left-sided tumors. In the CALGB/SWOG 80405 study, they all crossed over to FOLFIRI [irinotecan/5-FU/leucovorin] plus bevacizumab, if they got FOLFOX [oxaliplatin/5-FU/leucovorin] plus cetuximab. So I don’t see any contradiction in that at all. In second line, you know the response rates are so low with chemotherapy. The role, even of an EGFR inhibitor there, it’s not going to have as good of a response as it does in the frontline, so I don’t have a problem with that.


Transcript Edited for Clarity
 

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Transcript: 

Johanna C. Bendell, MD:
So, now turning to the other 85% of the population, we talked about a lot of these rare patients. So I love asking this question of Dirk first, because you have been put on the hot seat—no pun intended—many times to speak about this. You have a left-sided RAS wild-type patient, first-line therapy. What’s your go-to?

Dirk Arnold, MD, PhD: Well, that’s a clear indication for an anti-EGF receptor antibody. So from a European perspective, it’s a no-brainer that these patients should be treated with an anti-EGFR in combination with a doublet chemotherapy.

Heinz-Josef Lenz, MD, FACP: You tell him.

Dirk Arnold, MD, PhD: I tell him.

Johanna C. Bendell, MD: Do you purposely choose an irinotecan-based treatment over an oxaliplatin-based treatment?

Dirk Arnold, MD, PhD: Depends. I think it’s still open. I think it’s a bit about handling management of toxicity, etc. Since there is some overlap in toxicity with the skin toxicity and neuropathy with oxaliplatin, some feel more familiar to use them or feel safer to use them with an irinotecan-based chemotherapy, but it works either way.

Johanna C. Bendell, MD: OK. Zev, you live in LA [Los Angeles], where the beautiful people are. What would your choice be for treating a first-line left-sided RAS wild-type patient?

Zev A. Wainberg, MD: So, I used to use much more bevacizumab [Avastin], obviously, but I actually started to use more EGFR inhibitors in that kind of patient too. I find the data compelling. I find it reproducible, and I’m not going to say every patient is necessarily starting on an EGFR. But definitely, my own personal use of an EGFR inhibitor has gone up dramatically in the frontline setting in left-sided tumors over the last few years.

Johanna C. Bendell, MD: Now, do you get any pushback from your patients about the rash?

Zev A. Wainberg, MD: We do. We get pushback. But the rash now I find easier to deal with than it has ever been with prophylactic antibiotics and with aggressive skin management. Actually, many times I find the rash to be less of a problem than just the dryness of the skin. The rash itself is OK when they’re on antibiotics. It’s the dryness of the skin that is somewhat cumulative, which is a struggle, particularly in Southern California. But nonetheless, you have enough data now to suggest a survival advantage in some of these cohorts. So I think that has compelled a lot of people to move more in that direction.

Johanna C. Bendell, MD: Now then, what do you do for second line. Do you ever bring bevacizumab in?

Zev A. Wainberg, MD: Bevacizumab in second line, yes. I mean, I still think that there’s a role for bevacizumab in second line, even in left-sided tumors. In the CALGB/SWOG 80405 study, they all crossed over to FOLFIRI [irinotecan/5-FU/leucovorin] plus bevacizumab, if they got FOLFOX [oxaliplatin/5-FU/leucovorin] plus cetuximab. So I don’t see any contradiction in that at all. In second line, you know the response rates are so low with chemotherapy. The role, even of an EGFR inhibitor there, it’s not going to have as good of a response as it does in the frontline, so I don’t have a problem with that.


Transcript Edited for Clarity
 
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Oncology Briefings™: Individualizing Treatment After Second-Line Therapy for Patients With mCRCAug 29, 20191.0
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