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Current and Future Biomarker Testing in Lung Cancer

Panelists: Gerald J. Berry, MD, Stanford University; David Spigel, MD, Sarah Cannon Research Institute; Heather Wakelee, MD, Stanford University; Anne S. Tsao, MD, MD Anderson Cancer Center
Published Online: Monday, Jun 12, 2017



Transcript:

Anne S. Tsao, MD:
In nonsquamous non–small cell lung cancer, we typically do a genetic profile panel. At our institution, we do get a full panel for the genetic mutations, but it is generally recommended that you cover EGFR mutation, ALK mutation, and—I would argue—PD-L1 immunohistochemistry.

For some of the other mutations, I do recommend looking for BRAF mutations, V600E mutations, and ROS1 mutations. We also like to test for the MET exon 14 skipping mutation because we do have FDA-approved agents for other tumor types that can be used for these patients to help treat their cancer. In addition, RET mutations can be treated off protocol or on a clinical study. So, I think it’s very important to look for all of these mutations in our patients.

Heather Wakelee, MD: In my practice, which is in northern California, I have a very high percentage of patients who have actionable driver mutations, so we are testing all of our patients at the point of diagnosis. I’m waiting until a few days from now, when I’ll be able to know what to treat a patient with who was just diagnosed this week. So, I think it’s really critical that we think about testing at the point of diagnosis for all of our patients with advanced stage disease and also retesting for patients who weren’t found to have a driver mutation or who had a driver mutation and then developed a resistance. It’s important to retest, especially in that setting.

Gerald J. Berry, MD: What’s new and what’s coming, in terms biomarkers in cancer therapy and cancer diagnostics, I think there’s a 2-fold answer to that. There’s a tremendous amount of information that’s currently available through biomarkers. In fact, there’s probably too much information, and now we’re in that phase of trying to sift through and sort out what’s important and what’s not important.

So, for example, the whole of PD-L1 testing right now is an alphabet soup of testing because there are at least 4 different drugs. There are 4 different antibodies associated with each of those drugs. The clones for those antibodies are different. Some require that they be done on specific testing platforms, and so there’s an attempt underway to try and evaluate and compare and contract these different antibodies to see if some have a better sensitivity than others. I think those tests are still ongoing. There are some preliminary data, but I think there are still ongoing data that need to be done. So, I think we’ve got a lot of information now, and much of our effort is trying to distill that information, to combine it with molecular testing results and other modalities to try and then figure out the best options for the patient.

In terms of up-and-coming biomarkers, certainly much of the biomarker investigation has been directed toward adenocarcinomas. I think now there has been some very interesting work done to look to see if there are particular biomarkers for squamous cell carcinomas. And it looks as though there are some encouraging data with regard to the fibroblastic growth factor receptors, the PTENs, and the PIK3 gene alterations. So, I think that’s quite preliminary.

I think that, hopefully, in time, the squamous cell therapeutics will catch up with all of the different options that we currently have available for adenocarcinomas. That said, we already have PD-L1 in place for squamous cell carcinomas, but I think some of these other novel factors are up-and-coming.

Transcript Edited for Clarity
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Transcript:

Anne S. Tsao, MD:
In nonsquamous non–small cell lung cancer, we typically do a genetic profile panel. At our institution, we do get a full panel for the genetic mutations, but it is generally recommended that you cover EGFR mutation, ALK mutation, and—I would argue—PD-L1 immunohistochemistry.

For some of the other mutations, I do recommend looking for BRAF mutations, V600E mutations, and ROS1 mutations. We also like to test for the MET exon 14 skipping mutation because we do have FDA-approved agents for other tumor types that can be used for these patients to help treat their cancer. In addition, RET mutations can be treated off protocol or on a clinical study. So, I think it’s very important to look for all of these mutations in our patients.

Heather Wakelee, MD: In my practice, which is in northern California, I have a very high percentage of patients who have actionable driver mutations, so we are testing all of our patients at the point of diagnosis. I’m waiting until a few days from now, when I’ll be able to know what to treat a patient with who was just diagnosed this week. So, I think it’s really critical that we think about testing at the point of diagnosis for all of our patients with advanced stage disease and also retesting for patients who weren’t found to have a driver mutation or who had a driver mutation and then developed a resistance. It’s important to retest, especially in that setting.

Gerald J. Berry, MD: What’s new and what’s coming, in terms biomarkers in cancer therapy and cancer diagnostics, I think there’s a 2-fold answer to that. There’s a tremendous amount of information that’s currently available through biomarkers. In fact, there’s probably too much information, and now we’re in that phase of trying to sift through and sort out what’s important and what’s not important.

So, for example, the whole of PD-L1 testing right now is an alphabet soup of testing because there are at least 4 different drugs. There are 4 different antibodies associated with each of those drugs. The clones for those antibodies are different. Some require that they be done on specific testing platforms, and so there’s an attempt underway to try and evaluate and compare and contract these different antibodies to see if some have a better sensitivity than others. I think those tests are still ongoing. There are some preliminary data, but I think there are still ongoing data that need to be done. So, I think we’ve got a lot of information now, and much of our effort is trying to distill that information, to combine it with molecular testing results and other modalities to try and then figure out the best options for the patient.

In terms of up-and-coming biomarkers, certainly much of the biomarker investigation has been directed toward adenocarcinomas. I think now there has been some very interesting work done to look to see if there are particular biomarkers for squamous cell carcinomas. And it looks as though there are some encouraging data with regard to the fibroblastic growth factor receptors, the PTENs, and the PIK3 gene alterations. So, I think that’s quite preliminary.

I think that, hopefully, in time, the squamous cell therapeutics will catch up with all of the different options that we currently have available for adenocarcinomas. That said, we already have PD-L1 in place for squamous cell carcinomas, but I think some of these other novel factors are up-and-coming.

Transcript Edited for Clarity
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Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Clinical Application of Biomarker Testing in NSCLCAug 02, 20172.0
Community Practice Connections™: Oncogenic Tumor Board in NSCLC: Targeting Driver Mutations to Maximize Therapeutic OutcomesAug 31, 20171.5
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