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Osimertinib in EGFR-Positive NSCLC With Brain Metastases

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: Friday, Jul 27, 2018



Transcript: 

Benjamin P. Levy, MD: We see that this drug crosses the blood-brain barrier. It can elicit responses. Does that change the way that we manage patients who come in, are treatment-naïve, and have de novo brain metastases? If they are EGFR positive, given that we have this data, what’s our comfort level with starting osimertinib and not referring them to radiation therapy? Is there some way that we can follow these patients carefully and just give them osimertinib or do we need to send patients to radiation therapy?

Zofia Piotrowska, MD: Definitely, with the introduction of osimertinib, and it’s great seeing this activity, we have moved away from radiation whenever we can avoid it. Of course, there are patients who are highly symptomatic. In those cases, radiation is sometimes necessary. But for many patients with small asymptomatic brain metastases, we will try to get them on to osimertinib as quickly as possible and will do short-term follow-up to make sure that they’re responding appropriately. Certainly, as a field, we’re generally moving away from whole-brain radiation therapy for these patients and even targeted therapy. I think the other take-home message is that patients are living for a longer period of time than ever before. They’re young patients. They experience and notice the side effects of radiation. When you’re living for years with those side effects, it can really become quite meaningful. So, I try to avoid radiation and move to the CNS-penetrant drugs whenever possible. I’m sure that’s something we’ll cover again in the other sections, as well, with other targets.

Lyudmila A. Bazhenova, MD: The data of osimertinib support us. If you look at the FLAURA study, the CNS response rate with osimertinib was 81%. The complete response rate was 13%. Those are not small numbers. I think we will move away from just sending everybody to radiation right away. As long as you follow that patient, I would recommend not getting an MRI for 4 months after you started osimertinib; but if you follow it very closely, I think it’s very reasonable.

Jonathan W. Riess, MD, MS: I agree. I think that you should try to spare whole-brain radiation in these patients. New drugs are developing. Sparing them from the effects that can sometimes be devastating, that can occur years after getting whole-brain radiation, is really critical in these often young patients.

Benjamin P. Levy, MD: Yes. I’m on board with what everyone is saying here. I think there are patients who may need whole-brain radiation therapy up front, who are heavily symptomatic with edema where I may not feel comfortable starting them on a TKI. But I think this builds on the story that we’ve learned for erlotinib and the first- and second-generation TKIs. These drugs do cross the blood-brain barrier. I think osimertinib has done a better job at that and, certainly, at eliciting responses in the brain. In patients with asymptomatic brain metastases, I have felt more comfortable starting them on osimertinib and following them, without having them move to radiation.

Zofia Piotrowska, MD: I would add that I do this in close collaboration with my radiation oncology colleagues. These are patients who I will refer early to radiation. Even if I don’t think that they need radiation up front, I want to have radiation kind of following along and helping me to make decisions—as to whether the response we are seeing is adequate, when to get the follow up MRIs, and those types of things.

Transcript Edited for Clarity

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Transcript: 

Benjamin P. Levy, MD: We see that this drug crosses the blood-brain barrier. It can elicit responses. Does that change the way that we manage patients who come in, are treatment-naïve, and have de novo brain metastases? If they are EGFR positive, given that we have this data, what’s our comfort level with starting osimertinib and not referring them to radiation therapy? Is there some way that we can follow these patients carefully and just give them osimertinib or do we need to send patients to radiation therapy?

Zofia Piotrowska, MD: Definitely, with the introduction of osimertinib, and it’s great seeing this activity, we have moved away from radiation whenever we can avoid it. Of course, there are patients who are highly symptomatic. In those cases, radiation is sometimes necessary. But for many patients with small asymptomatic brain metastases, we will try to get them on to osimertinib as quickly as possible and will do short-term follow-up to make sure that they’re responding appropriately. Certainly, as a field, we’re generally moving away from whole-brain radiation therapy for these patients and even targeted therapy. I think the other take-home message is that patients are living for a longer period of time than ever before. They’re young patients. They experience and notice the side effects of radiation. When you’re living for years with those side effects, it can really become quite meaningful. So, I try to avoid radiation and move to the CNS-penetrant drugs whenever possible. I’m sure that’s something we’ll cover again in the other sections, as well, with other targets.

Lyudmila A. Bazhenova, MD: The data of osimertinib support us. If you look at the FLAURA study, the CNS response rate with osimertinib was 81%. The complete response rate was 13%. Those are not small numbers. I think we will move away from just sending everybody to radiation right away. As long as you follow that patient, I would recommend not getting an MRI for 4 months after you started osimertinib; but if you follow it very closely, I think it’s very reasonable.

Jonathan W. Riess, MD, MS: I agree. I think that you should try to spare whole-brain radiation in these patients. New drugs are developing. Sparing them from the effects that can sometimes be devastating, that can occur years after getting whole-brain radiation, is really critical in these often young patients.

Benjamin P. Levy, MD: Yes. I’m on board with what everyone is saying here. I think there are patients who may need whole-brain radiation therapy up front, who are heavily symptomatic with edema where I may not feel comfortable starting them on a TKI. But I think this builds on the story that we’ve learned for erlotinib and the first- and second-generation TKIs. These drugs do cross the blood-brain barrier. I think osimertinib has done a better job at that and, certainly, at eliciting responses in the brain. In patients with asymptomatic brain metastases, I have felt more comfortable starting them on osimertinib and following them, without having them move to radiation.

Zofia Piotrowska, MD: I would add that I do this in close collaboration with my radiation oncology colleagues. These are patients who I will refer early to radiation. Even if I don’t think that they need radiation up front, I want to have radiation kind of following along and helping me to make decisions—as to whether the response we are seeing is adequate, when to get the follow up MRIs, and those types of things.

Transcript Edited for Clarity
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