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Molecular Testing for Newly Diagnosed mCRC

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:
Let’s turn now to metastatic disease. For people who have been diagnosed with metastases, we’re going to ask the same question that we asked initially for adjuvant therapy for the earlier-stage disease. Heinz, I’m coming back to you again: Does your answer change? You have a patient come in with metastatic disease, previously untreated: What do you have to test for? What could you test for? And what are the sprinkles on the sundae that you’d want for, maybe, clinical trials in the future?

Heinz-Josef Lenz, MD, FACP: I like sprinkles.

Johanna C. Bendell, MD: Sprinkles are good.

Heinz-Josef Lenz, MD, FACP: The minimum basis when you look at the treatment implication has to be RAS, MSI, and BRAF mutations. There is an increasing motion to include HER2 gene testing for ongoing clinical trials, at least in the United States. It was the whole next-gen sequencing panel. It may be important, not so much for the decision of the first-line treatments but also for subsequent treatments, depending on your target and the access to clinical trials.

My sprinkle is genome sequencing. It sounds completely out of control, because we are doing that in a research project, but the first data I got back were incredible, because mutations are missed. The sensitivity and deepness of sequencing is different. That is actually under the germline and on the tumor. I made treatment decisions based on the whole genome, which I didn’t see in the NGS. I wouldn’t recommend doing so, but what I’m saying is, you asked for the sprinkles.

Johanna C. Bendell, MD: That is the sprinkles. Now back to reality in Europe. Dirk, what’s your absolute necessity and sprinkles?

Dirk Arnold, MD, PhD: There’s no difference. We implemented RAS testing across Europe much earlier than was established in the United States. We do tests and recommend BRAF testing as per the European Society of Medical Oncology [ESMO] Guidelines. Of course, MSI [microsatellite instability] testing has become more popular, although we have differences in access to checkpoint inhibitors, as you know, since MSI-high patients may be receiving treatment more easily in the United States. In Europe, it’s simply not available and it’s not registered, despite the fact that penitents may be MSI high, at least at the time being. Hopefully, it will change quite early.

Johanna C. Bendell, MD: Do you check for the HER2 gene?

Dirk Arnold, MD, PhD: We do check for HER2, but we try to limit this a bit. It’s generally not done in the first-line setting. It’s mainly done in patients who are RAS wild-type and left sided. We have some clinical molecular characteristics that enhance the likelihood that patients may be candidates for HER2 amplification. In these patients, which underwent treatment, it’s very often done.

Zev A. Wainberg, MD: I agree. We do reflex testing and start with RAS and MSI. If it’s RAS mutated, we stop there, don’t do HER2, and if it’s RAS wild-type, then we do HER2 and a couple of other things. We also have an internal panel that runs 30 genes. I like Heinz’s sprinkles. We should start a franchise with Heinz’s sprinkles.

The NGS—I can’t tell you I do it on every patient. We do now on more patients than we ever used to, simply because of the interest and the availability of clinical trials, but I can’t say it’s routine on every patient, obviously.

Johanna C. Bendell, MD: What we’re coming down to is the value of tissue. If you’re a patient that’s been diagnosed with metastatic disease, maybe based on liver core biopsies, you have a certain amount of tissue that you have available. We need to preserve that tissue. For instance, regarding the next-generation sequencing, you’re usually able to get microsatellite instability, expanded RAS, and BRAF, as well as HER2 in some panels.

Heinz-Josef Lenz, MD, FACP: They all will have it.


Transcript Edited for Clarity
 

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Transcript: 

Johanna C. Bendell, MD:
Let’s turn now to metastatic disease. For people who have been diagnosed with metastases, we’re going to ask the same question that we asked initially for adjuvant therapy for the earlier-stage disease. Heinz, I’m coming back to you again: Does your answer change? You have a patient come in with metastatic disease, previously untreated: What do you have to test for? What could you test for? And what are the sprinkles on the sundae that you’d want for, maybe, clinical trials in the future?

Heinz-Josef Lenz, MD, FACP: I like sprinkles.

Johanna C. Bendell, MD: Sprinkles are good.

Heinz-Josef Lenz, MD, FACP: The minimum basis when you look at the treatment implication has to be RAS, MSI, and BRAF mutations. There is an increasing motion to include HER2 gene testing for ongoing clinical trials, at least in the United States. It was the whole next-gen sequencing panel. It may be important, not so much for the decision of the first-line treatments but also for subsequent treatments, depending on your target and the access to clinical trials.

My sprinkle is genome sequencing. It sounds completely out of control, because we are doing that in a research project, but the first data I got back were incredible, because mutations are missed. The sensitivity and deepness of sequencing is different. That is actually under the germline and on the tumor. I made treatment decisions based on the whole genome, which I didn’t see in the NGS. I wouldn’t recommend doing so, but what I’m saying is, you asked for the sprinkles.

Johanna C. Bendell, MD: That is the sprinkles. Now back to reality in Europe. Dirk, what’s your absolute necessity and sprinkles?

Dirk Arnold, MD, PhD: There’s no difference. We implemented RAS testing across Europe much earlier than was established in the United States. We do tests and recommend BRAF testing as per the European Society of Medical Oncology [ESMO] Guidelines. Of course, MSI [microsatellite instability] testing has become more popular, although we have differences in access to checkpoint inhibitors, as you know, since MSI-high patients may be receiving treatment more easily in the United States. In Europe, it’s simply not available and it’s not registered, despite the fact that penitents may be MSI high, at least at the time being. Hopefully, it will change quite early.

Johanna C. Bendell, MD: Do you check for the HER2 gene?

Dirk Arnold, MD, PhD: We do check for HER2, but we try to limit this a bit. It’s generally not done in the first-line setting. It’s mainly done in patients who are RAS wild-type and left sided. We have some clinical molecular characteristics that enhance the likelihood that patients may be candidates for HER2 amplification. In these patients, which underwent treatment, it’s very often done.

Zev A. Wainberg, MD: I agree. We do reflex testing and start with RAS and MSI. If it’s RAS mutated, we stop there, don’t do HER2, and if it’s RAS wild-type, then we do HER2 and a couple of other things. We also have an internal panel that runs 30 genes. I like Heinz’s sprinkles. We should start a franchise with Heinz’s sprinkles.

The NGS—I can’t tell you I do it on every patient. We do now on more patients than we ever used to, simply because of the interest and the availability of clinical trials, but I can’t say it’s routine on every patient, obviously.

Johanna C. Bendell, MD: What we’re coming down to is the value of tissue. If you’re a patient that’s been diagnosed with metastatic disease, maybe based on liver core biopsies, you have a certain amount of tissue that you have available. We need to preserve that tissue. For instance, regarding the next-generation sequencing, you’re usually able to get microsatellite instability, expanded RAS, and BRAF, as well as HER2 in some panels.

Heinz-Josef Lenz, MD, FACP: They all will have it.


Transcript Edited for Clarity
 
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