Lisa A. Carey, MD, FASCO: Let’s talk about a case. This is a 55-year-old woman with HR [hormone receptor]–negative, HER2 [human epidermal growth factor receptor 2]–positive metastatic breast cancer that was physiologically confirmed as metastasis in the liver. Her brain was imaged and was negative. She had THP [docetaxel, trastuzumab, pertuzumab] for 6 cycles, had a response, and then was put on HP [trastuzumab, pertuzumab] alone. That lasted for 18 months, and then the liver lesions regrew. She was put on T-DM1 [trastuzumab emtansine]. Some might argue to go back on THP [docetaxel, trastuzumab, pertuzumab], but in this case, she went to T-DM1 [trastuzumab emtansine], and it worked. One year after being on T-DM1 [trastuzumab emtansine], she suffers from headaches, dizziness, and confusion. She has a brain MRI that shows 2 brain metastases, the largest 2.1 cm, and she is systemically controlled with the T-DM1 [trastuzumab emtansine]. Let’s talk about how you approach brain metastases, and isolated brain metastases progression. Let’s talk about the guidelines and your own practice. Who wants to kick it off?

Reshma Mahtani, DO: I can. As we talk about a case like this, in a patient who has systemic control on T-DM1 [trastuzumab emtansine] and then develops brain metastases, the challenge, for me, is that we don’t have a crystal ball to know what the pace of brain metastases development is going to be in the future for this patient. Is this a harbinger of horrible progressive CNS [central nervous system] metastases in the future? In which case, putting a patient like this on tucatinib [Tukysa] wouldn’t be the guideline approach in the absence of systemic progression as well. Whether that would be the better option—or to treat locally with radiation and continue the systemic therapy, my preferred approach in this situation; or to treat the brain with radiation; control systemic disease; and continue T-DM1 [trastuzumab emtansine]—that’s what guideline recommendations would be.

As you follow these patients, you’ll see that the disease pace declares itself. At some point, you’ll notice whether the patient is having progression in the brain as the primary driver of the disease. If I kept seeing more brain metastases at every follow-up brain MRI, then I might be at the point, and motivated, to go ahead and make the switch to tucatinib. But at that time in the beginning, when you have that first brain MRI, you don’t understand the pace of brain progression that’s going to happen in the future. That’s the real challenge for me.

Lisa A. Carey, MD, FASCO: Yeah. That’s a good point. This is a symptomatic patient with big brain metastases. This isn’t the same as the incidental findings that people get. That’s a really good point. Lee, V.K., any addition to that? Guidelines say to treat locally, continue systemically, and maybe move to the next line if it happens again. Is that what you guys do?

Lee S. Schwartzberg, MD, FACP: I agree with Reshma. You have systemic control. This is the first finding, so you don’t know what the pace of the disease is going to be. When you have a lesion that’s relatively large but can be treated locally with stereotactic radiosurgery plus or minus surgery—if it’s symptomatic and has edema—you should follow these patients extremely carefully. For this case, I’d be imaging the brain at least every 8 weeks and watching. If new lesions appear, then I would have a low threshold for switching but if she goes 6 or 9 months and continues to have systemic therapy, systemic control, and CNS control, then you haven’t lost anything by watching these patients.

Lisa A. Carey, MD, FASCO: You’ve gained several months of experience before you had to make the change, so that’s an interesting point. V.K., anything to add?

Vijayakrishna Gadi, MD, PhD: I agree with all 3 of you 100%.

Lisa A. Carey, MD, FASCO: Yay! That’s our first case study. Wonderful. Thank you.

Reshma Mahtani, DO: Lisa, to bring up the point of ongoing trials, the HER2CLIMB-02 study, looking at T-DM1 [trastuzumab emtansine] plus tucatinib in the second line, is ongoing. This would be something that might be raised at this point.

Lisa A. Carey, MD, FASCO: That’s a good point. It’s a great trial for patients to address this issue.

Transcript Edited for Clarity