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Importance of HER2 Expression in CRC

Panelists: Johanna C. Bendell, MD, Sarah Cannon Research Institute; Cathy Eng, MD, FACP, The University of Texas MD Anderson Cancer Center; John L. Marshall, MD, The Ruesch Center for the Cure of GI Cancers ; Michael A. Morse, MD, Duke Cancer Institute; Dale R. Shepard, MD, PhD, FACP, Taussig Cancer Institute, Cleveland Clinic
Published: Tuesday, Apr 03, 2018



Transcript: 

John L. Marshall, MD: Other molecular tests?

Johanna C. Bendell, MD: HER2 testing.

John L. Marshall, MD: This is not a breast cancer discussion, right?

Johanna C. Bendell, MD: I know, thank goodness. I think of HER2 as what BRAF used to be. We were concerned. It was a small population of patients with a worse prognosis. And so, do you check BRAF? Do you not? I think HER2 is sort of coming along that way. Not that it’s a worse prognosis, and it’s a small percentage of patients, but this is a patient population that likely has another treatment option available to them—especially with ongoing clinical trials that are showing response rates of 35%, 40%. And when you look at the spider plots, they look very similar to immunotherapy, with targeted agent combinations, only.

Cathy Eng, MD, FACP: It’s associated with resistance, potentially, to anti-EGFR therapy. So, I think that’s important.

John L. Marshall, MD: So, if I have a patient with a HER2 mutation, I’m not going to give EGFR therapy? I think the data might say no, right?

Cathy Eng, MD, FACP: The data that was originally presented suggest that those patients don’t benefit from anti-EGFR therapy. But there’s an ongoing trial, for SWOG, specifically, in anti–EGFR-naive patients. Even if you’re on the control arm, you can basically go on to the investigational arm. That is allowed.

John L. Marshall, MD: HER2 frequency low, higher in rectals. It’s higher, like the opposite of MSI. Do I biopsy somebody to see if they’re HER2-positive?

Michael A. Morse, MD: Yes. If they’ve been treated with EGFR therapy, there’s certainly reason that they could now have HER2 overexpression.

John L. Marshall, MD: So, it is worth doing?

Michael A. Morse, MD: Absolutely.

John L. Marshall, MD: You should know it in everybody, right?

Michael A. Morse, MD: At least in refractory disease. Up front, I think it’s infrequent enough. Of course, if we’re already doing these expanded panels anyway, we’re going to have that information. But I think the key is to realize that even if it’s not there early, it could be there later.

John L. Marshall, MD: Does anybody care how I measure HER2?

Johanna C. Bendell, MD: Well, yes.

Cathy Eng, MD, FACP: Yes.

Johanna C. Bendell, MD: But I would actually pause really quickly. It depends what panel you’re sending off. If you’re sending a next-generation sequencing panel, you’re not going to get a HER2 IHC or FISH back. You’ll get HER2 mutations, which is a whole other ball of wax. That is another conversation to have.

John L. Marshall, MD: And it is less clear as to whether that correlates with benefit?

Johanna C. Bendell, MD: Correct.

John L. Marshall, MD: But these studies were done with IHC and FISH and not with…

Johanna C. Bendell, MD: Yes, and not with the mutation patients. There’s some thought that the mutation patients won’t benefit. But when you’re ordering that test, don’t think that you’re just getting the HER2 with it. So, make sure you order the right test. There are some out there that will do the IHC in connection with the next-generation sequencing.

Cathy Eng, MD, FACP: It’s important to mention that the SWOG 1613 study, that’s brand new and is opening up, is specifically for overexpression. It’s not for mutation.

John L. Marshall, MD: Yes.

Cathy Eng, MD, FACP: And it has to be centrally verified.

John L. Marshall, MD: OK. There’s no study. This comes back positive. It’s sitting in front of you. You measured by FISH. What drugs do I give? Who do I ask permission to give what drug? Do I give a single agent or a combination? What are you giving, if it’s you?

Johanna C. Bendell, MD: It looks like it’s a combination that you’re going to need to do. You can’t just do trastuzumab, alone. There are 2 trials out there.

Cathy Eng, MD, FACP: And not pertuzumab, alone, either.

Johanna C. Bendell, MD: You could do trastuzumab plus lapatinib or trastuzumab plus pertuzumab. Both are used in clinical trials, mostly in Italy, but one in the US. And then, I think there’s also Cooperative Group efforts. But it’s going to be a dual blockade.

John L. Marshall, MD: I’m a doctor. I’m as busy as could be. I know that they’re going to push back. I’m scared that I won’t get reimbursed for these drugs, if I prescribe them, even if I’ve got pre-authorization. Do I have to do this?

Dale R. Shepard, MD, PhD, FACP: Yes.

Michael A. Morse, MD: The response rates are high.

Cathy Eng, MD, FACP: In that original study, the median number of prior therapies was 4 or 5. The response rate of 30% was impressive, and they still had 2 complete responses.

Dale R. Shepard, MD, PhD, FACP: Yes.

Michael A. Morse, MD: Yes.

John L. Marshall, MD: Even risking that being reimbursed?

Michael A. Morse, MD: Yes.

John L. Marshall, MD: That’s a really big fear. It’s a real fear.

Cathy Eng, MD, FACP: To live, yes.

John L. Marshall, MD: Do you make the patient pay, if you had to pay yourself? Or would you pay?

Johanna C. Bendell, MD: For HER2 IHC?

John L. Marshall, MD: No.

Johanna C. Bendell, MD: For the drugs?

John L. Marshall, MD: For the drugs.

Cathy Eng, MD, FACP: I think we have to pursue all efforts to try to get the drug, in all fairness.

John L. Marshall, MD: A lot of times, those patients will be sent to us, institutions, because we either will eat it or we’ll figure out how to get paid.

Cathy Eng, MD, FACP: You can file an appeal for a second or third time.

John L. Marshall, MD: So, it’s worth doing everybody, right?

Dale R. Shepard, MD, PhD, FACP: Yes. It’s very reasonable. If they’re not comfortable, you can refer them to some place that may have more resources to try to get access.

Johanna C. Bendell, MD: It might be cheaper to fly for a trial than to pay for the drug.

John L. Marshall, MD: That’s right. There are some trials out there, right now, where you can get access. There is a study with a HER2-targeted therapy arm. They’re flying the patients to the sites, out there.

Transcript Edited for Clarity 

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Transcript: 

John L. Marshall, MD: Other molecular tests?

Johanna C. Bendell, MD: HER2 testing.

John L. Marshall, MD: This is not a breast cancer discussion, right?

Johanna C. Bendell, MD: I know, thank goodness. I think of HER2 as what BRAF used to be. We were concerned. It was a small population of patients with a worse prognosis. And so, do you check BRAF? Do you not? I think HER2 is sort of coming along that way. Not that it’s a worse prognosis, and it’s a small percentage of patients, but this is a patient population that likely has another treatment option available to them—especially with ongoing clinical trials that are showing response rates of 35%, 40%. And when you look at the spider plots, they look very similar to immunotherapy, with targeted agent combinations, only.

Cathy Eng, MD, FACP: It’s associated with resistance, potentially, to anti-EGFR therapy. So, I think that’s important.

John L. Marshall, MD: So, if I have a patient with a HER2 mutation, I’m not going to give EGFR therapy? I think the data might say no, right?

Cathy Eng, MD, FACP: The data that was originally presented suggest that those patients don’t benefit from anti-EGFR therapy. But there’s an ongoing trial, for SWOG, specifically, in anti–EGFR-naive patients. Even if you’re on the control arm, you can basically go on to the investigational arm. That is allowed.

John L. Marshall, MD: HER2 frequency low, higher in rectals. It’s higher, like the opposite of MSI. Do I biopsy somebody to see if they’re HER2-positive?

Michael A. Morse, MD: Yes. If they’ve been treated with EGFR therapy, there’s certainly reason that they could now have HER2 overexpression.

John L. Marshall, MD: So, it is worth doing?

Michael A. Morse, MD: Absolutely.

John L. Marshall, MD: You should know it in everybody, right?

Michael A. Morse, MD: At least in refractory disease. Up front, I think it’s infrequent enough. Of course, if we’re already doing these expanded panels anyway, we’re going to have that information. But I think the key is to realize that even if it’s not there early, it could be there later.

John L. Marshall, MD: Does anybody care how I measure HER2?

Johanna C. Bendell, MD: Well, yes.

Cathy Eng, MD, FACP: Yes.

Johanna C. Bendell, MD: But I would actually pause really quickly. It depends what panel you’re sending off. If you’re sending a next-generation sequencing panel, you’re not going to get a HER2 IHC or FISH back. You’ll get HER2 mutations, which is a whole other ball of wax. That is another conversation to have.

John L. Marshall, MD: And it is less clear as to whether that correlates with benefit?

Johanna C. Bendell, MD: Correct.

John L. Marshall, MD: But these studies were done with IHC and FISH and not with…

Johanna C. Bendell, MD: Yes, and not with the mutation patients. There’s some thought that the mutation patients won’t benefit. But when you’re ordering that test, don’t think that you’re just getting the HER2 with it. So, make sure you order the right test. There are some out there that will do the IHC in connection with the next-generation sequencing.

Cathy Eng, MD, FACP: It’s important to mention that the SWOG 1613 study, that’s brand new and is opening up, is specifically for overexpression. It’s not for mutation.

John L. Marshall, MD: Yes.

Cathy Eng, MD, FACP: And it has to be centrally verified.

John L. Marshall, MD: OK. There’s no study. This comes back positive. It’s sitting in front of you. You measured by FISH. What drugs do I give? Who do I ask permission to give what drug? Do I give a single agent or a combination? What are you giving, if it’s you?

Johanna C. Bendell, MD: It looks like it’s a combination that you’re going to need to do. You can’t just do trastuzumab, alone. There are 2 trials out there.

Cathy Eng, MD, FACP: And not pertuzumab, alone, either.

Johanna C. Bendell, MD: You could do trastuzumab plus lapatinib or trastuzumab plus pertuzumab. Both are used in clinical trials, mostly in Italy, but one in the US. And then, I think there’s also Cooperative Group efforts. But it’s going to be a dual blockade.

John L. Marshall, MD: I’m a doctor. I’m as busy as could be. I know that they’re going to push back. I’m scared that I won’t get reimbursed for these drugs, if I prescribe them, even if I’ve got pre-authorization. Do I have to do this?

Dale R. Shepard, MD, PhD, FACP: Yes.

Michael A. Morse, MD: The response rates are high.

Cathy Eng, MD, FACP: In that original study, the median number of prior therapies was 4 or 5. The response rate of 30% was impressive, and they still had 2 complete responses.

Dale R. Shepard, MD, PhD, FACP: Yes.

Michael A. Morse, MD: Yes.

John L. Marshall, MD: Even risking that being reimbursed?

Michael A. Morse, MD: Yes.

John L. Marshall, MD: That’s a really big fear. It’s a real fear.

Cathy Eng, MD, FACP: To live, yes.

John L. Marshall, MD: Do you make the patient pay, if you had to pay yourself? Or would you pay?

Johanna C. Bendell, MD: For HER2 IHC?

John L. Marshall, MD: No.

Johanna C. Bendell, MD: For the drugs?

John L. Marshall, MD: For the drugs.

Cathy Eng, MD, FACP: I think we have to pursue all efforts to try to get the drug, in all fairness.

John L. Marshall, MD: A lot of times, those patients will be sent to us, institutions, because we either will eat it or we’ll figure out how to get paid.

Cathy Eng, MD, FACP: You can file an appeal for a second or third time.

John L. Marshall, MD: So, it’s worth doing everybody, right?

Dale R. Shepard, MD, PhD, FACP: Yes. It’s very reasonable. If they’re not comfortable, you can refer them to some place that may have more resources to try to get access.

Johanna C. Bendell, MD: It might be cheaper to fly for a trial than to pay for the drug.

John L. Marshall, MD: That’s right. There are some trials out there, right now, where you can get access. There is a study with a HER2-targeted therapy arm. They’re flying the patients to the sites, out there.

Transcript Edited for Clarity 
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