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Managing Patients on TRK Inhibitors

Panelists: Benjamin Levy, MD, Johns Hopkins Sidney Kimmel Cancer Center, Sibley Memorial Hospitale; Mark Agulnik, MD, Northwestern University Feinberg School of Medicine; Marcia Brose, MD, PhD, University of Pennsylvania; Edward Kim, MD, Levine Cancer Institute, Atrium Health ; John Marshall, MD, Georgetown University; Philip Agop Philip, MD, PhD, FRCP, Barbara Ann Karmanos Cancer Institute
Published: Wednesday, May 15, 2019



Transcript: 

Benjamin P. Levy, MD: Before we talk about NGS [next-generation sequencing] testing, do people have experience with these drugs, larotrectinib? Has anyone treated a patient yet, or been involved in the treatment of patients with NTRK fusions on larotrectinib, or entrectinib for that matter? Personal anecdotal experience.

Marcia S. Brose, MD, PhD: I mentioned the patient who came in thinking that he had to get his affairs in order in 3 months. And, of course, that was 5 years ago. Now he complains bitterly about the CT [computed tomography] scans he has to have.

Edward S. Kim, MD: Life’s unfair.

Marcia S. Brose, MD, PhD: Right? He doesn’t like the number of times he has to actually come in and see me. What a wonderful problem to have. The adverse effect profile is very manageable, with dizziness being the main thing. I think he actually was one of the patients who was dose reduced because of that. He still has that, but it is really tolerable. And one interesting part about that is he’s now a complete responder for several years. Do you keep giving it, and for how long?

John L. Marshall, MD: I would.

Benjamin P. Levy, MD: Yes.

Marcia S. Brose, MD, PhD: Well, we are. But at some point, somebody might actually say, “Should we try a year off and see if it comes back?” I think that there might be data coming up. I think there are some people who may have had to stop for other reasons. But it will be interesting to see whether these complete responses….

Philip Agop Philip, MD, PhD, FRCP: We had a recent patient with pancreatic adenocarcinoma who went on a trial and was still within the window of 1.8 months, which is the time we see a response with these, or the first CT scan, basically. We haven’t done that yet.

Benjamin P. Levy, MD: Any other experience?

John L. Marshall, MD: We have a pancreas patient on the study, the larotrectinib study. This is my partner’s patient. The patient has been doing very well. So we’re all very proud. But I also think we share in that we were the funnel site in our region, as you guys were in your regions. And so, what I think is much less common is that general practicing oncologist out there who’s going to find one of these and use this. We all need this learning curve. I think the nice part about this is if you find the right fusion, the drug is pretty easy to give and the benefit rate is high. So it’s not a tricky thing to do once you’ve found it.

Philip Agop Philip, MD, PhD, FRCP: But unfortunately, you only can find it if you look for it.

Edward S. Kim, MD: Yes, we’ve actually enrolled 2 people onto entrectinib: One with brain metastases that had been multiply treated and is actually now stabilized from the drug, and another with glioblastoma. We see a ton of glioblastomas at our place, and so I think that’s an area where we’ll probably have the highest number of hits, to be very frank.

Benjamin P. Levy, MD: As a lung cancer doctor in the field of precision medicine, not to besmirch the other disease states here, I feel like we’re the leading edge of targeted therapy. Put this in the context of what you usually see for an ALK-rearranged lung cancer treated with alectinib. Similar response? Duration similar? Timing of response? Intracranial response? I know it’s an N of 2.

Edward S. Kim, MD: Yes, it’s an N of 2.

Benjamin P. Levy, MD: Is it a similar story as we’re seeing in the other genotype…?

Edward S. Kim, MD: The first patient had such refractory disease with radiation, SRS [stereotactic radiosurgery], etcetera, and that was more stabilization. And so, I thought, “Well, maybe it doesn’t work as well.” But the second patient had a pretty dramatic response. And so, I do think it is one, maybe. It’s hard to say things are osimertinib or alectinib, because those are just super drugs right now. But certainly, this is a very active drug and a great alternative to what the subsequent therapies would have been in these patient populations.

Transcript Edited for Clarity

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Transcript: 

Benjamin P. Levy, MD: Before we talk about NGS [next-generation sequencing] testing, do people have experience with these drugs, larotrectinib? Has anyone treated a patient yet, or been involved in the treatment of patients with NTRK fusions on larotrectinib, or entrectinib for that matter? Personal anecdotal experience.

Marcia S. Brose, MD, PhD: I mentioned the patient who came in thinking that he had to get his affairs in order in 3 months. And, of course, that was 5 years ago. Now he complains bitterly about the CT [computed tomography] scans he has to have.

Edward S. Kim, MD: Life’s unfair.

Marcia S. Brose, MD, PhD: Right? He doesn’t like the number of times he has to actually come in and see me. What a wonderful problem to have. The adverse effect profile is very manageable, with dizziness being the main thing. I think he actually was one of the patients who was dose reduced because of that. He still has that, but it is really tolerable. And one interesting part about that is he’s now a complete responder for several years. Do you keep giving it, and for how long?

John L. Marshall, MD: I would.

Benjamin P. Levy, MD: Yes.

Marcia S. Brose, MD, PhD: Well, we are. But at some point, somebody might actually say, “Should we try a year off and see if it comes back?” I think that there might be data coming up. I think there are some people who may have had to stop for other reasons. But it will be interesting to see whether these complete responses….

Philip Agop Philip, MD, PhD, FRCP: We had a recent patient with pancreatic adenocarcinoma who went on a trial and was still within the window of 1.8 months, which is the time we see a response with these, or the first CT scan, basically. We haven’t done that yet.

Benjamin P. Levy, MD: Any other experience?

John L. Marshall, MD: We have a pancreas patient on the study, the larotrectinib study. This is my partner’s patient. The patient has been doing very well. So we’re all very proud. But I also think we share in that we were the funnel site in our region, as you guys were in your regions. And so, what I think is much less common is that general practicing oncologist out there who’s going to find one of these and use this. We all need this learning curve. I think the nice part about this is if you find the right fusion, the drug is pretty easy to give and the benefit rate is high. So it’s not a tricky thing to do once you’ve found it.

Philip Agop Philip, MD, PhD, FRCP: But unfortunately, you only can find it if you look for it.

Edward S. Kim, MD: Yes, we’ve actually enrolled 2 people onto entrectinib: One with brain metastases that had been multiply treated and is actually now stabilized from the drug, and another with glioblastoma. We see a ton of glioblastomas at our place, and so I think that’s an area where we’ll probably have the highest number of hits, to be very frank.

Benjamin P. Levy, MD: As a lung cancer doctor in the field of precision medicine, not to besmirch the other disease states here, I feel like we’re the leading edge of targeted therapy. Put this in the context of what you usually see for an ALK-rearranged lung cancer treated with alectinib. Similar response? Duration similar? Timing of response? Intracranial response? I know it’s an N of 2.

Edward S. Kim, MD: Yes, it’s an N of 2.

Benjamin P. Levy, MD: Is it a similar story as we’re seeing in the other genotype…?

Edward S. Kim, MD: The first patient had such refractory disease with radiation, SRS [stereotactic radiosurgery], etcetera, and that was more stabilization. And so, I thought, “Well, maybe it doesn’t work as well.” But the second patient had a pretty dramatic response. And so, I do think it is one, maybe. It’s hard to say things are osimertinib or alectinib, because those are just super drugs right now. But certainly, this is a very active drug and a great alternative to what the subsequent therapies would have been in these patient populations.

Transcript Edited for Clarity
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