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Acting on Molecular Testing Results in NSCLC

Panelists: Joshua Bauml, MD, University of Pennsylvania; D. Ross Camidge, MD, University of Colorado School of Medicine; Robert Doebele, MD, PhD, University of Colorado School of Medicine; Benjamin Levy, MD, Johns Hopkins Sidney Kimmel Cancer Center; Zofia Piotrowska, MD, Harvard Medical School
Published: Friday, Jul 19, 2019



Transcript:

Benjamin Levy, MD: What is your role, Josh, within your institution as physician champion coordinating this and educating other members of the team about what the right spots are to biopsy? How much communication goes down within different members of the team to get this achieved?

Joshua Bauml, MD: We speak frequently with our pathologists. I work very closely with our interventional pulmonary team to talk about this to say, “Look, we need as much tissue as we can get.” And when our oncology consult service is seeing patients in the hospital and they have a patient who has lots of bone metastases, I think the temptation to say, “Oh well, just biopsy that and then we’ll get everything we need.” We counsel our Fellows and talk with the people who are on service to say, “Please don’t do that because it’s really going to cause a problem later on.”

Benjamin Levy, MD: There’s a lot of onus I think on the medical oncologist to make sure this gets executed in the right way and at least identify someone in the institution as a part of the team to be a physician champion who can carry this out because it’s getting more complicated as we need more tissue for comprehensive genomic profiling. I want to mention a piece of data and get people’s thoughts about what’s going on.

We had a publication mining some real-world data recently published in JAMA Oncology looking at about 4000 patients, non–small cell lung cancer patients, mining again electronic health records [EHRs]. And of those 4000, roughly 1200 patients had an identifiable target that was identified within the medical record. But only about half of those patients ended up getting a targeted therapy. These were patients who had enough tissue, who had completed molecular testing, who had a biomarker identified. These are real-world data, and only half of those patients ended up getting a targeted therapy. What do we think is going on out there and how do we get the message across?

D. Ross Camidge, MD: There are a couple of things I’m going to ask you there. The first thing is what stage were the patients?

Benjamin Levy, MD: These were advanced-stage patients.

D. Ross Camidge, MD: OK, that’s the first thing. And then, the second thing is, what were these identified abnormalities, because often when you see these bits where people are saying, “Oh, look what our assay picked up,” what they’re reporting as actionable are things like, well, KRAS until today wasn’t an actionable abnormality, and TP53 and all these other things that aren’t really actionable.

Benjamin Levy, MD: These were NCCN [National Comprehensive Cancer Network] guideline biomarkers recommended for targeted therapies. This is not KRAS, these were druggable mutations that were captured within the EHR and then looking at whether these patients got a targeted therapy or not. This is real-world, this is within, a lot in the community. Half of these patients didn’t get targeted therapies, and I’m just curious about people’s thoughts of what may be going on and where is the gap there.

Robert Doebele, MD, PhD: I think there are a few things that could be going on. If you look specifically, for example, at EGFR, there are some mutations that currently don’t have approved therapies like exon 20 insertions. That could be a reflection of a community oncologist in the system understanding that perhaps EGFR TKIs [tyrosine kinase inhibitors] are not the best first therapy, although there are emerging trial data in this area to support, hopefully, eventual use of this. I think the other worry is that they’re not waiting for that testing to come back, so they’re doing the test and they’re starting chemotherapy. And then for one reason or another, they’re not making it on the targeted therapy once chemotherapy stops working. And I think that’s one of the concerns.

Joshua Bauml, MD: If they were given chemotherapy and immunotherapy, for instance, then there’s reason to believe that they might have increased toxicity if they have EGFR-mutated disease. It really is important for us to give the best possible therapy first, and so waiting for that molecular data I think is critical. I think that not waiting for the results is probably the issue. But the other issue that does arise is that when you look at these test reports, it can be dizzying. And for a busy clinician who’s seeing lots of patients with different types of tumors, that can be very overwhelming to know exactly where to go with that data. I think that that could also be a major problem.

Robert Doebele, MD, PhD: A lot of patients can really wait for this testing to come back, too. And there are some temporizing measures. If a patient has really bad pleural disease, consider thoracentesis or a VATS [video-assisted thoracoscopic surgery] pleurodesis; that’s a good therapeutic intervention while you’re waiting for testing to come back. If they have brain metastases, perhaps SRS [stereotactic radiosurgery] to a dominant lesion. There are some things you can do to help the patient while you’re waiting for the results. If they’re borderline, you can check in with the patients to make sure that they’re doing OK on a frequent basis, to make sure they don’t immediately need therapy.

Zofia Piotrowska, MD: I think that’s so important, too, for patient anxiety, of course. You’re a patient, you get told you have lung cancer, of course you want to start treatment. I think we all would. But I’ve often found that if you really explain the reason why it’s important to wait for the testing and about making sure we’re picking the best first therapy for these patients, and explaining to them that you’re going to follow them closely, maybe see them weekly, check in with them and manage that anxiety, I think for the vast majority of patients it’s doable. Sure, there are patients where you can’t wait and then you have to think about how to approach that.

D. Ross Camidge, MD: I’ve found that it doesn’t make great health economic sense, but if you send off the cfDNA [cell-free DNA], the circulating blood, at the same time, sometimes that’s coming back in a week. If it’s there I can act on it. If it’s not, I’ve already started the process for the tissue.

Joshua Bauml, MD: The other thing that you can do if you have a highly symptomatic patient who’s the appropriate patient population is that, we’ve discussed NGS [next-generation sequencing] can take 2 weeks, and that can take time. But if you have a patient who is a young, never-smoker, with highly symptomatic disease, I will call my pathologist and say, can we do a PCR [polymerase chain reaction] for EGFR and a FISH [fluorescence in situ hybridization] for ALK, and those tests can happen very quickly. So, if you have a symptomatic patient, there’s not always a need to jump in, and there you’re using more tissue, but it means you’ll have an answer much faster. And I’ve found that to be very helpful.

Transcript Edited for Clarity

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Transcript:

Benjamin Levy, MD: What is your role, Josh, within your institution as physician champion coordinating this and educating other members of the team about what the right spots are to biopsy? How much communication goes down within different members of the team to get this achieved?

Joshua Bauml, MD: We speak frequently with our pathologists. I work very closely with our interventional pulmonary team to talk about this to say, “Look, we need as much tissue as we can get.” And when our oncology consult service is seeing patients in the hospital and they have a patient who has lots of bone metastases, I think the temptation to say, “Oh well, just biopsy that and then we’ll get everything we need.” We counsel our Fellows and talk with the people who are on service to say, “Please don’t do that because it’s really going to cause a problem later on.”

Benjamin Levy, MD: There’s a lot of onus I think on the medical oncologist to make sure this gets executed in the right way and at least identify someone in the institution as a part of the team to be a physician champion who can carry this out because it’s getting more complicated as we need more tissue for comprehensive genomic profiling. I want to mention a piece of data and get people’s thoughts about what’s going on.

We had a publication mining some real-world data recently published in JAMA Oncology looking at about 4000 patients, non–small cell lung cancer patients, mining again electronic health records [EHRs]. And of those 4000, roughly 1200 patients had an identifiable target that was identified within the medical record. But only about half of those patients ended up getting a targeted therapy. These were patients who had enough tissue, who had completed molecular testing, who had a biomarker identified. These are real-world data, and only half of those patients ended up getting a targeted therapy. What do we think is going on out there and how do we get the message across?

D. Ross Camidge, MD: There are a couple of things I’m going to ask you there. The first thing is what stage were the patients?

Benjamin Levy, MD: These were advanced-stage patients.

D. Ross Camidge, MD: OK, that’s the first thing. And then, the second thing is, what were these identified abnormalities, because often when you see these bits where people are saying, “Oh, look what our assay picked up,” what they’re reporting as actionable are things like, well, KRAS until today wasn’t an actionable abnormality, and TP53 and all these other things that aren’t really actionable.

Benjamin Levy, MD: These were NCCN [National Comprehensive Cancer Network] guideline biomarkers recommended for targeted therapies. This is not KRAS, these were druggable mutations that were captured within the EHR and then looking at whether these patients got a targeted therapy or not. This is real-world, this is within, a lot in the community. Half of these patients didn’t get targeted therapies, and I’m just curious about people’s thoughts of what may be going on and where is the gap there.

Robert Doebele, MD, PhD: I think there are a few things that could be going on. If you look specifically, for example, at EGFR, there are some mutations that currently don’t have approved therapies like exon 20 insertions. That could be a reflection of a community oncologist in the system understanding that perhaps EGFR TKIs [tyrosine kinase inhibitors] are not the best first therapy, although there are emerging trial data in this area to support, hopefully, eventual use of this. I think the other worry is that they’re not waiting for that testing to come back, so they’re doing the test and they’re starting chemotherapy. And then for one reason or another, they’re not making it on the targeted therapy once chemotherapy stops working. And I think that’s one of the concerns.

Joshua Bauml, MD: If they were given chemotherapy and immunotherapy, for instance, then there’s reason to believe that they might have increased toxicity if they have EGFR-mutated disease. It really is important for us to give the best possible therapy first, and so waiting for that molecular data I think is critical. I think that not waiting for the results is probably the issue. But the other issue that does arise is that when you look at these test reports, it can be dizzying. And for a busy clinician who’s seeing lots of patients with different types of tumors, that can be very overwhelming to know exactly where to go with that data. I think that that could also be a major problem.

Robert Doebele, MD, PhD: A lot of patients can really wait for this testing to come back, too. And there are some temporizing measures. If a patient has really bad pleural disease, consider thoracentesis or a VATS [video-assisted thoracoscopic surgery] pleurodesis; that’s a good therapeutic intervention while you’re waiting for testing to come back. If they have brain metastases, perhaps SRS [stereotactic radiosurgery] to a dominant lesion. There are some things you can do to help the patient while you’re waiting for the results. If they’re borderline, you can check in with the patients to make sure that they’re doing OK on a frequent basis, to make sure they don’t immediately need therapy.

Zofia Piotrowska, MD: I think that’s so important, too, for patient anxiety, of course. You’re a patient, you get told you have lung cancer, of course you want to start treatment. I think we all would. But I’ve often found that if you really explain the reason why it’s important to wait for the testing and about making sure we’re picking the best first therapy for these patients, and explaining to them that you’re going to follow them closely, maybe see them weekly, check in with them and manage that anxiety, I think for the vast majority of patients it’s doable. Sure, there are patients where you can’t wait and then you have to think about how to approach that.

D. Ross Camidge, MD: I’ve found that it doesn’t make great health economic sense, but if you send off the cfDNA [cell-free DNA], the circulating blood, at the same time, sometimes that’s coming back in a week. If it’s there I can act on it. If it’s not, I’ve already started the process for the tissue.

Joshua Bauml, MD: The other thing that you can do if you have a highly symptomatic patient who’s the appropriate patient population is that, we’ve discussed NGS [next-generation sequencing] can take 2 weeks, and that can take time. But if you have a patient who is a young, never-smoker, with highly symptomatic disease, I will call my pathologist and say, can we do a PCR [polymerase chain reaction] for EGFR and a FISH [fluorescence in situ hybridization] for ALK, and those tests can happen very quickly. So, if you have a symptomatic patient, there’s not always a need to jump in, and there you’re using more tissue, but it means you’ll have an answer much faster. And I’ve found that to be very helpful.

Transcript Edited for Clarity
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