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Managing Brain Mets in Melanoma

Panelists: Jeffrey S. Weber, MD, PhD, Laura and Isaac Perlmutter Cancer Center; Robert Andtbacka, MD, CM, Huntsman Cancer Institute; Omid Hamid, MD, The Angeles Clinic and Research Institute ; Jason J. Luke, MD, FACP, University of Chicago; Michael A. Postow, MD, Memorial Sloan Kettering Cancer Center; Hussein Tawbi, MD, PhD, UT MD Anderson Cancer Center
Published: Wednesday, Sep 05, 2018



Transcript: 

Jeffrey S. Weber, MD, PhD: Hussein, you probably know as much as anyone about the treatment of melanoma with brain metastases. At the 2018 ASCO Annual Meeting, we are hearing an update on the Australian report. It’s recently published. You’ve certainly seen a lot of data from the CheckMate-204 study. How does that change practice? How has the data impacted on how you treat patients? Has it impacted the community?

Hussein Tawbi, MD, PhD: That’s a great question. I can actually add to the 3 Rs that Michael spoke about, in terms of the choice of ipilimumab/nivolumab. Maybe we can say “B” for “brain metastases.” The data are now quite consistent across multiple trials. The use of single-agent PD-1 gives you a response rate. It’s safe, and it gives you a response rate in the brain. But it’s in the order of about 20%, as opposed to extracranial disease where you can see rates from 35% to 40%. For the ipilimumab/nivolumab combination regimen, again, it’s safe. We don’t induce as much increased brain edema, with concerns that you may actually worsen your patients’ neurologic condition. We’ve established that it’s been safe in a couple hundred patients who have been treated across multiple trials.

The most important aspect is that the response rate is actually maintained. You get a response rate of 55% to 58%, which is consistent with extracranial disease, and those responses are actually durable. Some of them are complete responses, which, again, is very important. If these patients don’t have disease in the brain anymore, you do not need to radiate. You do not need to operate with all of the neurologic deficits that can come with that. So, we do believe that that is practice-changing. We’ve generally been delaying the start of immunotherapy in patients with brain metastases until the brain is controlled with radiation, SRS, or even surgery.

I should add that BRAF-targeted therapy has shown activity in the brain as well. For BRAF-mutated patients, that is an option. The response rates are also somewhat comparable, about 58%. The main difference is that the responses are actually less durable compared to the extracranial responses, and the progression-free survival is more limited to around 5 months. The way we stagger our approach is, if you’re a brain metastasis patient, I don’t ask if you’re BRAF-mutated or not. If I feel that it’s safe to start you on ipilimumab/nivolumab, that would usually be my first choice. If you progress through that or if you can’t tolerate treatment, or if you have other reasons not to start on ipilimumab/nivolumab, then I would consider BRAF-targeted therapy for a BRAF-mutant patient.

Jeffrey S. Weber, MD, PhD: Does that upset your neurosurgical colleagues to do the stereotactic radiosurgery?

Hussein Tawbi, MD, PhD: That’s actually a great question. In fact, they’ve been very excited about these results. We’ve actually developed a multidisciplinary approach around this. Every patient with brain metastases is discussed in a brain metastases tumor board, where we actually stagger our approaches and say which would be the best first thing to start with. And sometimes it’s me that rules them out and says, “Let’s go with immunotherapy first.” I think this data really kind of gives credence to this approach, and I think our neurosurgical colleagues and radiation oncologists are on board with that or are getting onboard with it at least.

Transcript Edited for Clarity

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Transcript: 

Jeffrey S. Weber, MD, PhD: Hussein, you probably know as much as anyone about the treatment of melanoma with brain metastases. At the 2018 ASCO Annual Meeting, we are hearing an update on the Australian report. It’s recently published. You’ve certainly seen a lot of data from the CheckMate-204 study. How does that change practice? How has the data impacted on how you treat patients? Has it impacted the community?

Hussein Tawbi, MD, PhD: That’s a great question. I can actually add to the 3 Rs that Michael spoke about, in terms of the choice of ipilimumab/nivolumab. Maybe we can say “B” for “brain metastases.” The data are now quite consistent across multiple trials. The use of single-agent PD-1 gives you a response rate. It’s safe, and it gives you a response rate in the brain. But it’s in the order of about 20%, as opposed to extracranial disease where you can see rates from 35% to 40%. For the ipilimumab/nivolumab combination regimen, again, it’s safe. We don’t induce as much increased brain edema, with concerns that you may actually worsen your patients’ neurologic condition. We’ve established that it’s been safe in a couple hundred patients who have been treated across multiple trials.

The most important aspect is that the response rate is actually maintained. You get a response rate of 55% to 58%, which is consistent with extracranial disease, and those responses are actually durable. Some of them are complete responses, which, again, is very important. If these patients don’t have disease in the brain anymore, you do not need to radiate. You do not need to operate with all of the neurologic deficits that can come with that. So, we do believe that that is practice-changing. We’ve generally been delaying the start of immunotherapy in patients with brain metastases until the brain is controlled with radiation, SRS, or even surgery.

I should add that BRAF-targeted therapy has shown activity in the brain as well. For BRAF-mutated patients, that is an option. The response rates are also somewhat comparable, about 58%. The main difference is that the responses are actually less durable compared to the extracranial responses, and the progression-free survival is more limited to around 5 months. The way we stagger our approach is, if you’re a brain metastasis patient, I don’t ask if you’re BRAF-mutated or not. If I feel that it’s safe to start you on ipilimumab/nivolumab, that would usually be my first choice. If you progress through that or if you can’t tolerate treatment, or if you have other reasons not to start on ipilimumab/nivolumab, then I would consider BRAF-targeted therapy for a BRAF-mutant patient.

Jeffrey S. Weber, MD, PhD: Does that upset your neurosurgical colleagues to do the stereotactic radiosurgery?

Hussein Tawbi, MD, PhD: That’s actually a great question. In fact, they’ve been very excited about these results. We’ve actually developed a multidisciplinary approach around this. Every patient with brain metastases is discussed in a brain metastases tumor board, where we actually stagger our approaches and say which would be the best first thing to start with. And sometimes it’s me that rules them out and says, “Let’s go with immunotherapy first.” I think this data really kind of gives credence to this approach, and I think our neurosurgical colleagues and radiation oncologists are on board with that or are getting onboard with it at least.

Transcript Edited for Clarity
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Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Evolving Roles for Targeted Melanoma Therapies: Assessing Rapid Progress in the Field and Looking Toward Future CombinationsFeb 28, 20191.5
Advances in™ Melanoma: Exploring BRAF/MEK in Adjuvant and Neoadjuvant SettingsSep 28, 20191.5
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