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Response Rates in Treatment of MET-Amplified NSCLC

Panelists: Benjamin P. Levy, MD, Sibley Memorial Hospital; Shirish M. Gadgeel, MD, University of Michigan; Lyudmila A. Bazhenova, MD, UCSD Morris Cancer Center; Anne S. Tsao, MD, MD Anderson Cancer Center; Mohammad Jahanzeb, MD, FACP, University of Miami, Miller School of Medicine
Published: Tuesday, Nov 20, 2018



Transcript: 

Benjamin P. Levy, MD:
Let’s move on for the sake of time to another mutation which we’re questioning. Anne, do you want to talk also about the importance or lack thereof of MET [tyrosine kinase receptor] amplification and how we use that in everyday practice in our patients?

Anne S. Tsao, MD: This is a tough one because all of us have known about MET amplification since it was considered to be a possible resistant mechanism to the EGFR [epidermal growth factor receptor] inhibitors during the early stages of lung cancer research. We had several drugs—MET and mAbs [monoclonal antibodies]—which we thought were going to yield high efficacy, which they didn’t.

Benjamin P. Levy, MD: These two showed a lot of promise.

Anne S. Tsao, MD: It was certainly a disappointment. It’s important to distinguish, again, genetic mutations from gene copy numbers gained. There is the MET exon 14 skip mutation, which everybody should consider treating with crizotinib. [There’re] also data showing possibilities with alectinib [Alecensa]. That, without a doubt, should be considered a standard practice.

Mohammad Jahanzeb, MD, FACP: Actionable.

Anne S. Tsao, MD: Actionable mutations. What this abstract from ASCO [American Society of Clinical Oncology] showed was that patients with MET amplification are different: These were patients who had more than 1 copy number of the gene and amplification along different levels. They considered it low, medium, or high and used different rations to determine the level of gene amplification a patient had, and they treated these patients with crizotinib, which is known as a MET inhibitor. The interesting thing about this in the low and high levels was the rate of responsiveness, which ranged from 33% to 40%.

And so for this population of patients, which we don’t have a lot of great targeted options for, I certainly would consider giving crizotinib to a patient with MET amplification after they progressed on chemotherapy or any other reasonable regimen.

Benjamin P. Levy, MD: We certainly used it in some patients who were post TKI [tyrosine kinase inhibitor] for the EGFR space if they’re MET amplified and off label. This is not approved, and I certainly think chemotherapy is the right choice in these patients—but have in some instances been able to do get that approved. I don’t think, however, that it should be done routinely.
Any other thoughts on MET amplification and its role?

Lyudmila A. Bazhenova, MD:
When you get the report from whatever company you use, and it says, “MET Amplification,” it typically doesn’t mention the amplification, so you might want to give them a phone call; they will then be able to tell you the amplification number. After I’ve administered standard treatment and I still see MET amplification, I don’t see why I shouldn’t try crizotinib, for example. The data presented at ASCO, though, showed a small frequency of use. The fact that the low and high performed similarly makes me think that this could be a numbers game. But past [the] second-line and third-line, we have no start-up care, which is why I think it’s a reasonable option.

Shirish M. Gadgeel, MD: That brings up an important point that you mentioned in the report. I can tell you that it is common to not understand some of the results that are mentioned. I don’t think a physician should feel shy about calling the lab and seeking clarification on the results, because I think sometimes we feel as if it’s not actionable, whereas it may be.

Anne S. Tsao, MD:
Absolutely. And we actually do MET FISH [fluorescence in situ hybridizations] because there are several agents under development, that we probably don’t have time to go into, that are specifically trying to target this, because MET is such an easy target to go after.


Transcript Edited for Clarity
 

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Transcript: 

Benjamin P. Levy, MD:
Let’s move on for the sake of time to another mutation which we’re questioning. Anne, do you want to talk also about the importance or lack thereof of MET [tyrosine kinase receptor] amplification and how we use that in everyday practice in our patients?

Anne S. Tsao, MD: This is a tough one because all of us have known about MET amplification since it was considered to be a possible resistant mechanism to the EGFR [epidermal growth factor receptor] inhibitors during the early stages of lung cancer research. We had several drugs—MET and mAbs [monoclonal antibodies]—which we thought were going to yield high efficacy, which they didn’t.

Benjamin P. Levy, MD: These two showed a lot of promise.

Anne S. Tsao, MD: It was certainly a disappointment. It’s important to distinguish, again, genetic mutations from gene copy numbers gained. There is the MET exon 14 skip mutation, which everybody should consider treating with crizotinib. [There’re] also data showing possibilities with alectinib [Alecensa]. That, without a doubt, should be considered a standard practice.

Mohammad Jahanzeb, MD, FACP: Actionable.

Anne S. Tsao, MD: Actionable mutations. What this abstract from ASCO [American Society of Clinical Oncology] showed was that patients with MET amplification are different: These were patients who had more than 1 copy number of the gene and amplification along different levels. They considered it low, medium, or high and used different rations to determine the level of gene amplification a patient had, and they treated these patients with crizotinib, which is known as a MET inhibitor. The interesting thing about this in the low and high levels was the rate of responsiveness, which ranged from 33% to 40%.

And so for this population of patients, which we don’t have a lot of great targeted options for, I certainly would consider giving crizotinib to a patient with MET amplification after they progressed on chemotherapy or any other reasonable regimen.

Benjamin P. Levy, MD: We certainly used it in some patients who were post TKI [tyrosine kinase inhibitor] for the EGFR space if they’re MET amplified and off label. This is not approved, and I certainly think chemotherapy is the right choice in these patients—but have in some instances been able to do get that approved. I don’t think, however, that it should be done routinely.
Any other thoughts on MET amplification and its role?

Lyudmila A. Bazhenova, MD:
When you get the report from whatever company you use, and it says, “MET Amplification,” it typically doesn’t mention the amplification, so you might want to give them a phone call; they will then be able to tell you the amplification number. After I’ve administered standard treatment and I still see MET amplification, I don’t see why I shouldn’t try crizotinib, for example. The data presented at ASCO, though, showed a small frequency of use. The fact that the low and high performed similarly makes me think that this could be a numbers game. But past [the] second-line and third-line, we have no start-up care, which is why I think it’s a reasonable option.

Shirish M. Gadgeel, MD: That brings up an important point that you mentioned in the report. I can tell you that it is common to not understand some of the results that are mentioned. I don’t think a physician should feel shy about calling the lab and seeking clarification on the results, because I think sometimes we feel as if it’s not actionable, whereas it may be.

Anne S. Tsao, MD:
Absolutely. And we actually do MET FISH [fluorescence in situ hybridizations] because there are several agents under development, that we probably don’t have time to go into, that are specifically trying to target this, because MET is such an easy target to go after.


Transcript Edited for Clarity
 
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