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Identifying Rare Mutations in NSCLC

Insights From: Edward B. Garon, MD, David Geffen School of Medicine at UCLA; Alexander Spira, MD, PhD, FACP, US Oncology Virginia Cancer Specialists
Published: Friday, Nov 08, 2019



Transcript: 

Alexander Spira, MD, PhD, FACP:
Exon 14 skipping mutations in the MET gene are relatively rare. They occur in only about 4% of lung cancer patients overall. Interestingly, while most of the driver mutations tend to occur in nonsmokers at a very high percentage—and it’s still the case with MET—only about 30% of patients with skipping mutations in the MET gene are nonsmokers. The patients tend to be a little bit of an older population. Average age of onset is still around 60. They tend to be adenocarcinomas, although interestingly, they can be in any subtype of non–small cell lung cancer. And it interestingly makes up about 20% to 30% of sarcomatoid lung cancer, which is a very rare subtype but is uniquely seen in that group.

Exon 14 skipping mutations in MET are very important to look for and very important to understand. Obviously, we know about the major drivers: EGFR, ALK, ROS, etc. But this is relatively new, and it’s very important to identify because there are drugs in development that can be used, in addition to some off-label drugs that can now be used as well to treat this. So it’s really important to test for it and understand that it exists.

Edward B. Garon, MD: There’s significant debate as to what the appropriate molecular testing is for individual patients. In my part of the country, in the United States, there’s a strong penetration of Kaiser. Kaiser has had a focus on cost-effective care.

They have said that either there’s an approved therapy for a specific target or it is a research test. And so some drivers over time, of course, change from a research test to a clinical test. EGFR has been a clinical test for a long time. ALK also has been a clinical test for a long time. ROS1 followed those as a clinical test. And now BRAF is clearly a clinical test that needs to be performed, because there are FDA-approved therapies that are given for BRAF-mutant non–small cell lung cancer.

But it becomes trickier over time. NTRK mutations are seen very uncommonly in lung cancer, but they are seen. And so now there is an approved therapy. There are other mutations that are looking quite promising in clinical trials. The MET exon 14 skipping mutation is 1 of them, but is not the only 1. RET would be another example of a target for which clinical trials of agents look quite promising.
If one draws a firm line, one would say those are research tests. In my clinic, I view them more like clinical tests. And this is a continuum that keeps shifting as more and more is understood about various mutations. I think we are probably entering a period in which there will continue to be debate over how broadly to test patients for these mutations. But one thing I think everyone recognizes is important is if there are approved therapeutics against a target, patients should be tested so that they can have access to those agents.


Transcript Edited for Clarity
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Transcript: 

Alexander Spira, MD, PhD, FACP:
Exon 14 skipping mutations in the MET gene are relatively rare. They occur in only about 4% of lung cancer patients overall. Interestingly, while most of the driver mutations tend to occur in nonsmokers at a very high percentage—and it’s still the case with MET—only about 30% of patients with skipping mutations in the MET gene are nonsmokers. The patients tend to be a little bit of an older population. Average age of onset is still around 60. They tend to be adenocarcinomas, although interestingly, they can be in any subtype of non–small cell lung cancer. And it interestingly makes up about 20% to 30% of sarcomatoid lung cancer, which is a very rare subtype but is uniquely seen in that group.

Exon 14 skipping mutations in MET are very important to look for and very important to understand. Obviously, we know about the major drivers: EGFR, ALK, ROS, etc. But this is relatively new, and it’s very important to identify because there are drugs in development that can be used, in addition to some off-label drugs that can now be used as well to treat this. So it’s really important to test for it and understand that it exists.

Edward B. Garon, MD: There’s significant debate as to what the appropriate molecular testing is for individual patients. In my part of the country, in the United States, there’s a strong penetration of Kaiser. Kaiser has had a focus on cost-effective care.

They have said that either there’s an approved therapy for a specific target or it is a research test. And so some drivers over time, of course, change from a research test to a clinical test. EGFR has been a clinical test for a long time. ALK also has been a clinical test for a long time. ROS1 followed those as a clinical test. And now BRAF is clearly a clinical test that needs to be performed, because there are FDA-approved therapies that are given for BRAF-mutant non–small cell lung cancer.

But it becomes trickier over time. NTRK mutations are seen very uncommonly in lung cancer, but they are seen. And so now there is an approved therapy. There are other mutations that are looking quite promising in clinical trials. The MET exon 14 skipping mutation is 1 of them, but is not the only 1. RET would be another example of a target for which clinical trials of agents look quite promising.
If one draws a firm line, one would say those are research tests. In my clinic, I view them more like clinical tests. And this is a continuum that keeps shifting as more and more is understood about various mutations. I think we are probably entering a period in which there will continue to be debate over how broadly to test patients for these mutations. But one thing I think everyone recognizes is important is if there are approved therapeutics against a target, patients should be tested so that they can have access to those agents.


Transcript Edited for Clarity
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