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Rationale for Liquid Biopsies in NSCLC

Panelists: Benjamin P. Levy, MD, Johns Hopkins Sidney Kimmel Cancer Center; Lyudmila A. Bazhenova, MD, University of California San Diego; Alexander Drilon, MD, Memorial Sloan Kettering Cancer Center; Zofia Piotrowska, MD, Massachusetts General Hospital Cancer Center; Jonathan W. Riess, MD, MS, UC Davis Comprehensive Cancer Center
Published: Thursday, Sep 20, 2018



Transcript: 

Benjamin P. Levy, MD: We talked a little about this when we were talking about tissue plasma—the comfortability of people using plasma. Let’s say you have a patient who walks in. A biopsy is done. It’s non–small cell lung cancer, but it’s not able to be genotyped any further. It’s stage IV, based on a PET scan. Do people feel comfortable reflexing to plasma rather than sending for another biopsy, or do they do both? Or do they just send for another rebiopsy? Is there a best-practice pattern here or a best way to approach this?

Alexander Drilon, MD: I don’t know that there’s a best-practice pattern. Different doctors do different things. I prefer to do both at the same time. My take on liquid biopsies is that you can get an answer back very quickly. It’s very useful when you find something. But when you don’t find something, it doesn’t mean that it’s not there. Further testing should be done. In my mind, I think you should start the clock on both the plasma and the tumor testing and not wait for it to be done later. But people practice differently.

Benjamin P. Levy, MD: Any other thoughts on plasma?

Zofia Piotrowska, MD: I think there are certain places where there are approved indications—for example, in the setting of EGFR-mutant lung cancers and testing for T790M. That is actually an approved indication. If you find it in the plasma, you can treat with osimertinib. But again, I think the key point is, if you don’t find it, tissue should still be the next step. A negative plasma test doesn’t really mean that the patient is T790M negative. They could just be in a situation where they are not shedding enough DNA.

Benjamin P. Levy, MD: I agree. Nobody has drunk the plasma Kool-Aid more than I have. I really enjoy what it’s done, particularly in terms of genotyping these patients. But I think we need to be careful, not only in terms of the false negatives. The plasma test is a complex biospecimen. There are a lot of things in there, and we’re not sure where they’re coming from. And they may have some false positives as well. We have to be careful of the interpretability of these reports and what they mean. Certainly, not only looking at plasma as a static piece of information, I think there’s some future for looking at it in a longitudinal, dynamic way—in looking at changes in plasma levels with targeted therapies as early indicators of patients responding or not. I think there’s a lot of promise in that.
This has been an extremely informative panel discussion. Before we end, I’d like to hear some final thoughts from each of our panelists. Dr. Bazhenova?

Lyudmila A. Bazhenova, MD: There is a saying, “Location, location, location.” I would say, “Testing, testing, testing.”

Benjamin P. Levy, MD: OK. That is a good point. Alex?

Alexander Drilon, MD: I’m going to pursue a similar theme and say, “Tissue is the issue.” In order to do “testing, testing, testing,” you have to acquire enough tissue to do that. There’s also the plasma angle, as we mentioned, that’s complementary to those tumor tests.

Benjamin P. Levy, MD: Zofia?

Zofia Piotrowska, MD: I’m struck by the fact that across these different tumor types, when you have good drugs, they’re most effective in the earlier-line settings. As we develop better therapies, we’re really going to have to keep testing them in earlier lines of treatment, moving them to the frontline when possible. That seems to be true for EGFR and ALK and hopefully for other rearrangements and mutations as well.

Benjamin P. Levy, MD: Jonathan?

Jonathan W. Riess, MD, MS: I agree. Putting your best drugs first, particularly for EGFR and ALK, with activity against brain metastases, has really improved patient outcomes. I think that’s been an incredible advance. We’re still not curing patients, but it’s a step in the right direction.

Benjamin P. Levy, MD: Yes. In the world of the immunotherapy craze, my final impressions are “Be careful.” Genotype these patients first. At this time, single-agent immunotherapy probably doesn’t fit. Specifically, for EGFR and ALK, these probably are not the best settings for delivering immunotherapy. Certainly, we’ve learned this at this year’s ASCO Annual Meeting.

Thank you for all your contributions to this discussion. On behalf of our panel, we thank you for joining us. We hope that you found this Peer Exchange® discussion to be useful and informative.

Transcript Edited for Clarity 

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Transcript: 

Benjamin P. Levy, MD: We talked a little about this when we were talking about tissue plasma—the comfortability of people using plasma. Let’s say you have a patient who walks in. A biopsy is done. It’s non–small cell lung cancer, but it’s not able to be genotyped any further. It’s stage IV, based on a PET scan. Do people feel comfortable reflexing to plasma rather than sending for another biopsy, or do they do both? Or do they just send for another rebiopsy? Is there a best-practice pattern here or a best way to approach this?

Alexander Drilon, MD: I don’t know that there’s a best-practice pattern. Different doctors do different things. I prefer to do both at the same time. My take on liquid biopsies is that you can get an answer back very quickly. It’s very useful when you find something. But when you don’t find something, it doesn’t mean that it’s not there. Further testing should be done. In my mind, I think you should start the clock on both the plasma and the tumor testing and not wait for it to be done later. But people practice differently.

Benjamin P. Levy, MD: Any other thoughts on plasma?

Zofia Piotrowska, MD: I think there are certain places where there are approved indications—for example, in the setting of EGFR-mutant lung cancers and testing for T790M. That is actually an approved indication. If you find it in the plasma, you can treat with osimertinib. But again, I think the key point is, if you don’t find it, tissue should still be the next step. A negative plasma test doesn’t really mean that the patient is T790M negative. They could just be in a situation where they are not shedding enough DNA.

Benjamin P. Levy, MD: I agree. Nobody has drunk the plasma Kool-Aid more than I have. I really enjoy what it’s done, particularly in terms of genotyping these patients. But I think we need to be careful, not only in terms of the false negatives. The plasma test is a complex biospecimen. There are a lot of things in there, and we’re not sure where they’re coming from. And they may have some false positives as well. We have to be careful of the interpretability of these reports and what they mean. Certainly, not only looking at plasma as a static piece of information, I think there’s some future for looking at it in a longitudinal, dynamic way—in looking at changes in plasma levels with targeted therapies as early indicators of patients responding or not. I think there’s a lot of promise in that.
This has been an extremely informative panel discussion. Before we end, I’d like to hear some final thoughts from each of our panelists. Dr. Bazhenova?

Lyudmila A. Bazhenova, MD: There is a saying, “Location, location, location.” I would say, “Testing, testing, testing.”

Benjamin P. Levy, MD: OK. That is a good point. Alex?

Alexander Drilon, MD: I’m going to pursue a similar theme and say, “Tissue is the issue.” In order to do “testing, testing, testing,” you have to acquire enough tissue to do that. There’s also the plasma angle, as we mentioned, that’s complementary to those tumor tests.

Benjamin P. Levy, MD: Zofia?

Zofia Piotrowska, MD: I’m struck by the fact that across these different tumor types, when you have good drugs, they’re most effective in the earlier-line settings. As we develop better therapies, we’re really going to have to keep testing them in earlier lines of treatment, moving them to the frontline when possible. That seems to be true for EGFR and ALK and hopefully for other rearrangements and mutations as well.

Benjamin P. Levy, MD: Jonathan?

Jonathan W. Riess, MD, MS: I agree. Putting your best drugs first, particularly for EGFR and ALK, with activity against brain metastases, has really improved patient outcomes. I think that’s been an incredible advance. We’re still not curing patients, but it’s a step in the right direction.

Benjamin P. Levy, MD: Yes. In the world of the immunotherapy craze, my final impressions are “Be careful.” Genotype these patients first. At this time, single-agent immunotherapy probably doesn’t fit. Specifically, for EGFR and ALK, these probably are not the best settings for delivering immunotherapy. Certainly, we’ve learned this at this year’s ASCO Annual Meeting.

Thank you for all your contributions to this discussion. On behalf of our panel, we thank you for joining us. We hope that you found this Peer Exchange® discussion to be useful and informative.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
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