Adam Brufsky, MD, PhD: Let’s say you have a woman who gets THP [paclitaxel, trastuzumab, pertuzumab] and she relapses in the brain, plus systemically. She has a new liver metastasis but 1 or 2 brain metastases. Let’s assume for the time being that she has 1 or 2 asymptomatic 1-cm brain metastases because you scanned her brain. How would you treat it? Would you give her tucatinib in that setting or not?
Virginia Kaklamani, MD:I would because that’s the only data that we have beside addressing the brain with local therapy, giving some radiosurgery, and all that. I don’t think it would be a bad idea, either. But the data that we have on DS-8201 [trastuzumab deruxtecan] is it’s a phase 2 trial and it’s not that many patients, whereas, tucatinib is a large phase 3 randomized trial, with way more sturdy data.
Adam Brufsky, MD, PhD: Agreed. Carey, what do you make of this whole brain business? How many progressive metastases that are asymptomatic would you be comfortable not giving radiotherapy to and just giving tucatinib to? That’s the question everybody who is watching this is going to be asking themselves. A woman comes in the door, she’s asymptomatic, and she also has a couple brain metastases. What do I do with her?
Carey K. Anders, MD: That would be a decision I’d certainly want to make with my local therapist. I would also want the radiation oncologist to also evaluate the patient, making certain the lesion is not in the pons because a brain stem lesion is going to be very different than a frontal lobe lesion. The location really matters as to whether or not you’re going to lead with systemic therapy in these smaller asymptomatic lesions as opposed to radiosurgery. For lesions that are in the millimeter sizes and not in eloquent areas, I would be very comfortable with the HER2CLIMB regimen as a lead in. Radiosurgery certainly comes with consequences of radiation therapy necrosis, 9, 12 months out from treatment. The good news is that many of our patients are living 2, 3, 4 years after their diagnosis of brain metastasis. We’re being very thoughtful about when we position radiosurgery for when it’s absolutely needed. It just highlights that multi-disciplinary evaluation of the patient, to make certain, as the medical oncologist, I’m not missing an area in the brain that needs immediate local therapy.
Adam Brufsky, MD, PhD: You don’t have a number in mind? Say a woman comes in with three 1-cm lesions, all noneloquent areas. Who knows eloquent?
Carey K. Anders, MD: I think you’re right. I don’t know that I have an absolute number in my head of number of lesions. I think any more than 4 or 5 and I’m going to start to get nervous. I do think the 1-cm cutoff is a reasonable cutoff. If you follow a 6-mm-or 7- mm lesion 3 months later, I would definitely adhere to at least 12 week, or maybe even earlier, 9 week re-imaging brain MRI, in the setting of an untreated lesion. Hopefully, you would not see doubling during that timeframe and if you did, that would be a time where you’d want to go ahead and initiate local therapy. I think subcentimeter, about 3 or less, is very reasonable for systemic therapy first.
Adam Brufsky, MD, PhD: Rashmi, was there a cutoff in the trial of the size? Erica Hamilton was telling us this story. You were there at that ad board when she said it. I treated an asymptomatic woman with a 4-cm brain metastasis and it went away. Was there really a limit, a size cutoff?
Rashmi K. Murthy, MD, MBE: There wasn’t a size cutoff but with discussion with the medical monitor, if the treating team felt like they wanted to defer local therapy because the patient was asymptomatic and didn’t require it for any urgent reason, they could actually get a pass on the size cutoff. I believe the size cutoff was 2 cm.
Adam Brufsky, MD, PhD: There is no number cutoff, right? You could have as many as you wanted.
Rashmi K. Murthy, MD, MBE: Yeah. There was no number cut off.
Adam Brufsky, MD, PhD: Mark, what would you do? Would you do that, too. Would you just treat anybody?
Mark D. Pegram, MD: If there was a large lesion or multiple large lesions, I would feel uncomfortable relying on systemic treatment. However, with post-clinical follow-up, and frequent re-imaging, I’m not completely opposed to it, but I would do it under the auspices of our neuro-oncology group. We basically have a tumor board equivalent with the neurosurgeon, with radiation therapists, and ourselves, and so it would be discussed, and we could adjudicate it that way with buying in from the patients.
Transcript Edited for Clarity