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The Importance of Comprehensive Genomic Profiling

Panelists:Benjamin P. Levy, MD, Mount Sinai Health Systems;Chandra P. Belani, MD, Penn State Cancer Institute;Marina Garassino, MD, National Cancer Institute Milan, Italy;Sarah B. Goldberg, MD, MPH, Yale Cancer Center;Ramaswamy Govindan, MD, Washington University School of Medicine;Mark G. Kris, MD, Memorial Sloan-Kettering Cancer Center
Published: Friday, Jul 22, 2016


Transcript:

Benjamin P. Levy, MD:
I understand the need and the role for molecular interrogation for lung cancer, and the importance of a physician champion. I think it’s incumbent upon us to really educate others so that we can get this done in an efficient and a timely way. My question to you is, are you testing all stages of disease or just stage 4? Is this something that we should just be testing every single patient that walks through our door, irrespective of their stage?

Mark G. Kris, MD: Who can walk into an oncologist’s office not getting a CBC? Do they all need a CBC? Maybe not. But it’s becoming the way that we do things. You don’t know exactly what you’re going to need on day one. And because these multiplex testing systems are so efficient, both in terms of cost and tissue utilization, it does make the most sense to just get it on everyone. Now, you don’t have a drug for every target for every patient in 2016, but that changes a lot; 2 or 3 years ago who knew we’d be looking for MET. And 4 years ago who knew we’d be looking for RET or ROS. So, these things happen really quickly, and I urge you to just do the same thing on everybody.

Benjamin P. Levy, MD: I can understand the importance of comprehensive genomic profiling. To be honest, this is something that we hadn’t been doing routinely, at least in our patient population, up until 2 years ago, via an in-house test. And I’ve been encouraged by what we have found. I think there are nice data to show that comprehensive genomic profiling can pick up on EGFR mutations that were missed on the first go-around. I guess the challenge here is, how do you interpret all the data that you get from a comprehensive genomic profiling testing platform, what do you do with all that information, and how to discern between a driver mutation and a passenger mutation? Can you comment on that?

Mark G. Kris, MD: If somebody does a CAT scan of their chest, do they say, “Do I really need to see the adrenal gland? I’m interested in the lung”? No. You get that information, you get what you need, and sometimes that’s really helpful. In a patient with lung cancer it’s really helpful. In somebody with idiopathic pulmonary fibrosis, it’s not that helpful. But you get it, and you process it.

Benjamin P. Levy, MD: I agree with you. I think that comprehensive genomic profiling should be performed on all stages of disease, even those early stages. In the event that a patient’s disease recurs, we will have that information from the surgically resected tissue at the time of surgery. So, let me ask you, what are some of the barriers that you’re experiencing at Memorial Sloan Kettering, or your perceived barriers in the community, in terms of tissue procurement?

Mark G. Kris, MD: The biggest hurdle, frankly, is communication. I was part of a tumor board yesterday with a pathologist and an interventional radiologist. And they both went out of their way to educate me on how much better a job they can do, and how much more efficiently they can do their job, when they get the right information from us. If I could give one message to the medical oncologists, it is to make sure you have a conversation with the interventional radiologist, with your pathologist, about exactly what you’re looking for. And I’ll guarantee you, you’ll end up getting more than you asked for. But they have to be put into the equation. I think that’s one thing that came out in the discussions I was involved in a day or so ago, and I’ve urged people to have those conversations.

Benjamin P. Levy, MD: So, does that resonate with you, Sarah? Is that your routine approach at Yale?

Sarah B. Goldberg, MD, MPH: Yes, I agree with what you’re saying. I think the ideal situation is to get a comprehensive genomic testing on all patients, and that’s what we’re trying to do at Yale as well. The reality of the situation in some cases is that you have a patient who needs to urgently know what we need to know, what mutations they have, because we need to start treatment quickly. I would say that on average, it’s quicker to get specific gene testing done than to get a more comprehensive panel, and that’s true at Yale. We could fairly easily get a more comprehensive panel, but it takes more time. Whereas, if we just want to look at a few mutations—EGFR, KRAS, ALK—we’re able to get that really, really quickly. And I imagine that’s the case in a lot of hospitals in the community as well.

So, if I have a patient that’s sick and I need to start treatments, I might consider getting a more targeted genomic testing of just these mutations that are immediately actionable, and I’ll know the answer within a few days. And then if that’s negative, I would be thinking about being broader. I would say that’s the only exception to trying to get more broad testing.

Mark G. Kris, MD: I agree with you. So, what our pathologists do now is, whenever you have a specimen for lung cancer, they immediately do an IHC test for ALK and EGFR, and L858R. Probably two-thirds of the most common things are done automatically by a pathologist. Again, I didn’t think this up. Our pathologists thought that up.

Sarah B. Goldberg, MD, MPH: That’s the fastest way to do it, yes.

Mark G. Kris, MD: We got the best of both worlds.

Benjamin P. Levy, MD: Marina, just a global perspective in terms of what you’re doing and how you’re implementing comprehensive genomic profiling in Italy, and perhaps what’s being done in Europe?

Marina Garassino, MD: The situation is that you can do a multiplex or a comprehensive panel in the compressive cancer center. But in the general hospitals, you have to do at least the ALK and EGFR, and then you can ask the comprehensive cancer center to get more. But we have a multiplex, too, and so we started to sequence. Sometimes you find, for example, directive information and you don’t have the clinical trial, which is really frustrating for the patient. There is also a psychological aspect. So that must be managed very well, in Italy at least.

Transcript Edited for Clarity
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Transcript:

Benjamin P. Levy, MD:
I understand the need and the role for molecular interrogation for lung cancer, and the importance of a physician champion. I think it’s incumbent upon us to really educate others so that we can get this done in an efficient and a timely way. My question to you is, are you testing all stages of disease or just stage 4? Is this something that we should just be testing every single patient that walks through our door, irrespective of their stage?

Mark G. Kris, MD: Who can walk into an oncologist’s office not getting a CBC? Do they all need a CBC? Maybe not. But it’s becoming the way that we do things. You don’t know exactly what you’re going to need on day one. And because these multiplex testing systems are so efficient, both in terms of cost and tissue utilization, it does make the most sense to just get it on everyone. Now, you don’t have a drug for every target for every patient in 2016, but that changes a lot; 2 or 3 years ago who knew we’d be looking for MET. And 4 years ago who knew we’d be looking for RET or ROS. So, these things happen really quickly, and I urge you to just do the same thing on everybody.

Benjamin P. Levy, MD: I can understand the importance of comprehensive genomic profiling. To be honest, this is something that we hadn’t been doing routinely, at least in our patient population, up until 2 years ago, via an in-house test. And I’ve been encouraged by what we have found. I think there are nice data to show that comprehensive genomic profiling can pick up on EGFR mutations that were missed on the first go-around. I guess the challenge here is, how do you interpret all the data that you get from a comprehensive genomic profiling testing platform, what do you do with all that information, and how to discern between a driver mutation and a passenger mutation? Can you comment on that?

Mark G. Kris, MD: If somebody does a CAT scan of their chest, do they say, “Do I really need to see the adrenal gland? I’m interested in the lung”? No. You get that information, you get what you need, and sometimes that’s really helpful. In a patient with lung cancer it’s really helpful. In somebody with idiopathic pulmonary fibrosis, it’s not that helpful. But you get it, and you process it.

Benjamin P. Levy, MD: I agree with you. I think that comprehensive genomic profiling should be performed on all stages of disease, even those early stages. In the event that a patient’s disease recurs, we will have that information from the surgically resected tissue at the time of surgery. So, let me ask you, what are some of the barriers that you’re experiencing at Memorial Sloan Kettering, or your perceived barriers in the community, in terms of tissue procurement?

Mark G. Kris, MD: The biggest hurdle, frankly, is communication. I was part of a tumor board yesterday with a pathologist and an interventional radiologist. And they both went out of their way to educate me on how much better a job they can do, and how much more efficiently they can do their job, when they get the right information from us. If I could give one message to the medical oncologists, it is to make sure you have a conversation with the interventional radiologist, with your pathologist, about exactly what you’re looking for. And I’ll guarantee you, you’ll end up getting more than you asked for. But they have to be put into the equation. I think that’s one thing that came out in the discussions I was involved in a day or so ago, and I’ve urged people to have those conversations.

Benjamin P. Levy, MD: So, does that resonate with you, Sarah? Is that your routine approach at Yale?

Sarah B. Goldberg, MD, MPH: Yes, I agree with what you’re saying. I think the ideal situation is to get a comprehensive genomic testing on all patients, and that’s what we’re trying to do at Yale as well. The reality of the situation in some cases is that you have a patient who needs to urgently know what we need to know, what mutations they have, because we need to start treatment quickly. I would say that on average, it’s quicker to get specific gene testing done than to get a more comprehensive panel, and that’s true at Yale. We could fairly easily get a more comprehensive panel, but it takes more time. Whereas, if we just want to look at a few mutations—EGFR, KRAS, ALK—we’re able to get that really, really quickly. And I imagine that’s the case in a lot of hospitals in the community as well.

So, if I have a patient that’s sick and I need to start treatments, I might consider getting a more targeted genomic testing of just these mutations that are immediately actionable, and I’ll know the answer within a few days. And then if that’s negative, I would be thinking about being broader. I would say that’s the only exception to trying to get more broad testing.

Mark G. Kris, MD: I agree with you. So, what our pathologists do now is, whenever you have a specimen for lung cancer, they immediately do an IHC test for ALK and EGFR, and L858R. Probably two-thirds of the most common things are done automatically by a pathologist. Again, I didn’t think this up. Our pathologists thought that up.

Sarah B. Goldberg, MD, MPH: That’s the fastest way to do it, yes.

Mark G. Kris, MD: We got the best of both worlds.

Benjamin P. Levy, MD: Marina, just a global perspective in terms of what you’re doing and how you’re implementing comprehensive genomic profiling in Italy, and perhaps what’s being done in Europe?

Marina Garassino, MD: The situation is that you can do a multiplex or a comprehensive panel in the compressive cancer center. But in the general hospitals, you have to do at least the ALK and EGFR, and then you can ask the comprehensive cancer center to get more. But we have a multiplex, too, and so we started to sequence. Sometimes you find, for example, directive information and you don’t have the clinical trial, which is really frustrating for the patient. There is also a psychological aspect. So that must be managed very well, in Italy at least.

Transcript Edited for Clarity
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