Case 3: Treatment Options for CNS Progression in HER2+ Breast Cancer


Experts in the management of breast cancer discuss the role of tucatinib in patients with brain metastases.

Sara Tolaney, MD, MPH: Just to be a little provocative, is this someone where you would think about tucatinib, given the survival benefit in patients with brain metastases, so you’d change systemic treatment?

Ingrid A. Mayer, MD, MSCI: I tend to agree with Carey on this one. This is somebody who’s obviously not curable. There’s not going to be a right or wrong here, but I certainly wouldn’t want to burn out a regimen that is working well. And if you have other means to control the CNS [central nervous system] disease that don’t involve changing therapies and possibly messing up what’s happening below the neck, I’d rather wait and put her on tucatinib, capecitabine, trastuzumab upon progression, regardless of what’s happening in the brain. At that point, I would use that as my next go-to line because this is somebody who has CNS disease, and there would be value in using the tucatinib regimen for preventing further CNS issues. But I wouldn’t necessarily feel compelled to think, “brain metastases, let’s switch.” No, if she had disease progression below the neck, no question, but without that, I do tend to agree with Carey. One thing I am curious about, though, is that I have changed my pattern in view of what’s out there and the more we learn about the biology of these cancers, is in the beginning, I didn’t a priori scan people’s brains upon diagnosis of HER2 disease or incorporate MRI, until they became symptomatic. But I started doing a baseline MRI, and an MRI every 6 months, on patients with HER2 metastatic disease, precisely to find stuff before it gets symptomatic and you can address it with stereotactic [radiosurgery]. That makes their trajectory a lot smoother than waiting until “surprise.” I confess that I have changed that practice, I didn’t use to and now I do, even though that’s probably not in the guidelines. I’m curious about what other people do?

Sara Tolaney, MD, MPH: Andy, I don’t know, is this something you’ve done?

Andrew Seidman, MD: I don’t do this as a habit, although I do wonder whether what Ingrid is suggesting might be ultimately our standard of care, and there are several trials, including in Boston and other places, that are examining the role of monitoring in the absence of neurological symptoms. It’ll be an interesting story. I would agree with both Carey and Ingrid that, to use another phrase, don’t shoot the horse you rode in on. I would continue Kadcyla in this case because there’s no progression outside the CNS, and because stereotactic radiosurgery [SRS] should be effective for these 2 lesions. If there was disease progression below the neck, then I’d be thinking about pivoting to the HER2CLIMB regimen, and I look forward to other studies that will inform us in terms of using tucatinib in a post-SRS setting.

Ingrid A. Mayer, MD, MSCI: To go back to that screening question, when the initial guidelines came in and said you do not need to do MRIs, if you remember, those are the times where CNS disease equaled you only have a year to live. This is no longer the case, especially for these women. I feel like women with HER2 metastatic cancer, some of them are even cured, and the ones who are not cured, they still have a ginormous disease trajectory. They’re alive for years, so we need to be very careful about preventing them from having whole brain RT [radiation therapy] as much as we can, because once they have whole brain RT, their quality of life 1 or 2 years after that is going to go down big time. I do see the value of potentially having actionability into finding something in the CNS early vs when it becomes symptomatic, because it does change quality of life and their disease trajectory, whereas before, maybe it didn’t. That’s why I shifted despite the guidelines. I’m not as purist as you, Carey, I’m a little rogue anyway.

Andrew Seidman, MD: So in Nashville, the insurance companies, they’re not paying for subcu [subcutaneous] Herceptin and Perjeta….

Ingrid A. Mayer, MD, MSCI: They pay for the MRIs.

Andrew Seidman, MD: But they pay for MRIs?

Ingrid A. Mayer, MD, MSCI: Yes.

Sara Tolaney, MD, MPH: How about Carey, how have you thought about screening here, and is it something you’re doing in asymptomatic patients ever, or how are you incorporating that?

Carey Anders, MD: Asymptomatic is probably a loose term. With any index of suspicion, we would order a brain MRI. Our patients have headaches, they have sinus disease, and when we do have other reasons for headaches, or maybe they’re struggling with, I had a patient with something as subtle as her handwriting was a little different, and she came in and it turns out she had brain metastasis. We have a very low threshold to screen. I can’t say that I do it like, it’s been 6 months, I’m going to do a brain MRI, but we have a very high index of suspicion, and we’ll screen at any symptom. I’m really curious to see the results of the screening MRI study because I agree with all that’s been said. This is about so many aspects of the patient’s care now, whether we can avoid whole brain radiation therapy for the patient altogether. We do have tools that we didn’t have even 2 years ago, and decisions, so I agree. The screening guidelines, our systemic therapies have outpaced the guidelines, and if you look at other diseases, like non–small cell lung cancer or small cell lung cancer, melanoma, where the rates of brain metastasis are pretty similar to HER2-positive breast cancer, it’s recommended to get an upfront brain MRI before you start therapy. We’ll catch up.

Sara Tolaney, MD, MPH: I agree. It’s interesting, because everyone’s brought up this point, it’s more than just about catching the brain metastasis. It’s also obviously a delay to neurological symptoms that could have such an impact on quality of life if we could catch it earlier. And so certainly some of these screening studies are powered to analyze that, because that is so critical if we could pick up tiny lesions rather than wait until we get larger symptomatic ones. Maybe we will change patients’ quality of life, and potentially even improve survival.

Andrew Seidman, MD: That’s a great point. The parallel for me is how much better we’re managing skeletal morbidity from the disease in the era of bisphosphonates and denosumab and earlier intervention for brain metastasis. We’re not seeing fractures in admissions for hypercalcemia in the bone world. Maybe we won’t be seeing seizures and change in mental status and paresis in the CNS world.

Transcript edited for clarity.

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