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Challenges With NGS for TRK Inhibition

Insights From: David S. Hong, MD, MD Anderson Cancer Center; Alexander Drilon, MD, Memorial Sloan Kettering Cancer Center; David Hyman, MD, Memorial Sloan Kettering Cancer Center
Published: Thursday, Jul 19, 2018



Transcript: 

David S. Hong, MD: I believe that reimbursement is going to be key in how next-generation sequencing is going to be utilized. Without reimbursement, I think it will not gain widespread traction across communities, community hospitals, and community oncologists. I think reimbursement is going to be key, ultimately, for that. I think one of the things that’s going to drive that is economies of scale and the actual cost of the underlying technology. If it gets to a certain threshold of cost, I think it will be reimbursed more readily.

David Hyman, MD: The turnaround times for next-generation sequencing have really been dropping. We see many of the commercial laboratories, depending on whether it’s a tumor-based or a blood-based test, returning results in as short as 2 weeks or sometimes even more quickly. Obviously, the turnaround time for a tumor-based test is often limited by the ability to locate the tumor and get it to the appropriate lab.

I think what’s really important is that as we have real drugs to offer patients as approved therapies in a tumor-agnostic manner, this testing should be done relatively early. When patients initially present with an advanced or an incurable cancer, that’s really when I would advocate for sending this test. If you wait for having exhausted all the standard options for that patient, you could potentially run into a problem where the test result comes back too late for the patient to benefit. We have seen examples of that, and it’s very heartbreaking when you see that happen.

When we have a patient who unfortunately develops metastatic cancer, we know that that patient is very likely to die from that cancer eventually. It seems that to maximize the chance of utility for this test, we plan ahead a little bit and order this test before we’re in a last-minute situation where 1 week could really make a difference.

Alexander Drilon, MD: Recognizing that next-generation sequencing with comprehensive assays can take a few weeks, when you sit down with a patient, it’s important to recognize whether or not they’re fit enough to wait for the most appropriate therapy. Considering that you might find a molecular signature that’s actionable in their cancer—or if you need the result—resort to standard-of-care therapy, like chemotherapy or immunotherapy for cases where patients may be sick. Certainly, in my practice and in my lung cancer clinic, I have patients who meet me and have a poor performance status that’s mostly mediated by advanced and widely metastatic disease. If I can’t get an answer off the next-generation sequencing, or even complementary plasma profiling or liquid biopsies, then I immediately jump to giving them chemotherapy that may hopefully turn things around.

Once I get the next-generation sequencing or complementary plasma testing results back, assuming the patient isn’t responding to therapy, I will then switch to targeted therapy or immunotherapy if appropriate. Or, if they’re responding well to the therapy that I instituted prior to the results of sequencing, if it ain’t broke, don’t fix it. Keep them on the same therapy and keep the matched therapy based on the results of sequencing in your back pocket for when they need to switch gears and do something different.

David S. Hong, MD: The turnaround time is something that we use in the context of, does it affect whether or not we immediately use next-generation sequencing testing? Clearly, there are some technologies like hotspot mutation analysis, which can be turned around within several days, versus NGS, which can take several weeks. I think it just depends on the platform and a number of issues. I think in the community, in some instances, you just can’t wait several weeks for a next-generation sequencing platform to turn around.

Oftentimes, in the community, they will order it in anticipation of a chemotherapy that is not going to work or a standard chemotherapy that may not work in the future, so that the patient may have alternatives later on. In my practice, which is primarily a clinical trials practice, for every patient who comes into our clinic—if they do not have an NGS panel—we do order an NGS panel that is available at MD Anderson. Part of that is because it will help us identify, if not early on but later, possible actionable mutations that we can use to enroll patients in clinical trials.

Transcript Edited for Clarity 
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Transcript: 

David S. Hong, MD: I believe that reimbursement is going to be key in how next-generation sequencing is going to be utilized. Without reimbursement, I think it will not gain widespread traction across communities, community hospitals, and community oncologists. I think reimbursement is going to be key, ultimately, for that. I think one of the things that’s going to drive that is economies of scale and the actual cost of the underlying technology. If it gets to a certain threshold of cost, I think it will be reimbursed more readily.

David Hyman, MD: The turnaround times for next-generation sequencing have really been dropping. We see many of the commercial laboratories, depending on whether it’s a tumor-based or a blood-based test, returning results in as short as 2 weeks or sometimes even more quickly. Obviously, the turnaround time for a tumor-based test is often limited by the ability to locate the tumor and get it to the appropriate lab.

I think what’s really important is that as we have real drugs to offer patients as approved therapies in a tumor-agnostic manner, this testing should be done relatively early. When patients initially present with an advanced or an incurable cancer, that’s really when I would advocate for sending this test. If you wait for having exhausted all the standard options for that patient, you could potentially run into a problem where the test result comes back too late for the patient to benefit. We have seen examples of that, and it’s very heartbreaking when you see that happen.

When we have a patient who unfortunately develops metastatic cancer, we know that that patient is very likely to die from that cancer eventually. It seems that to maximize the chance of utility for this test, we plan ahead a little bit and order this test before we’re in a last-minute situation where 1 week could really make a difference.

Alexander Drilon, MD: Recognizing that next-generation sequencing with comprehensive assays can take a few weeks, when you sit down with a patient, it’s important to recognize whether or not they’re fit enough to wait for the most appropriate therapy. Considering that you might find a molecular signature that’s actionable in their cancer—or if you need the result—resort to standard-of-care therapy, like chemotherapy or immunotherapy for cases where patients may be sick. Certainly, in my practice and in my lung cancer clinic, I have patients who meet me and have a poor performance status that’s mostly mediated by advanced and widely metastatic disease. If I can’t get an answer off the next-generation sequencing, or even complementary plasma profiling or liquid biopsies, then I immediately jump to giving them chemotherapy that may hopefully turn things around.

Once I get the next-generation sequencing or complementary plasma testing results back, assuming the patient isn’t responding to therapy, I will then switch to targeted therapy or immunotherapy if appropriate. Or, if they’re responding well to the therapy that I instituted prior to the results of sequencing, if it ain’t broke, don’t fix it. Keep them on the same therapy and keep the matched therapy based on the results of sequencing in your back pocket for when they need to switch gears and do something different.

David S. Hong, MD: The turnaround time is something that we use in the context of, does it affect whether or not we immediately use next-generation sequencing testing? Clearly, there are some technologies like hotspot mutation analysis, which can be turned around within several days, versus NGS, which can take several weeks. I think it just depends on the platform and a number of issues. I think in the community, in some instances, you just can’t wait several weeks for a next-generation sequencing platform to turn around.

Oftentimes, in the community, they will order it in anticipation of a chemotherapy that is not going to work or a standard chemotherapy that may not work in the future, so that the patient may have alternatives later on. In my practice, which is primarily a clinical trials practice, for every patient who comes into our clinic—if they do not have an NGS panel—we do order an NGS panel that is available at MD Anderson. Part of that is because it will help us identify, if not early on but later, possible actionable mutations that we can use to enroll patients in clinical trials.

Transcript Edited for Clarity 
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