Joyce A. O’Shaughnessy, MD: Sara, I have a few minutes for questions that have been coming in. I wanted to get to that important HER2 [human epidermal growth factor receptor 2]–positive metastatic setting because of new data that came out at ESMO [European Society for Medical Oncology Congress] and then were updated at San Antonio [Breast Cancer Symposium]. You’ve been very involved in this study, so we’re going to start with the case you submitted.

Sara A. Hurvitz, MD: We have a 40-year-old woman with an ER [estrogen receptor] and PR [progesterone receptor]–negative and HER2+ de novo metastatic breast cancer involving the liver with multiple lesions, and lung, bones, and large left breast mass with lymphadenopathy—disease everywhere. She receives first-line taxane-trastuzumab-pertuzumab, and after 2 cycles has a complete response, except for the bones, where we still saw some evidence of prior metastases. She completes 6 cycles of the taxane-trastuzumab-pertuzumab and goes on to the maintenance HP [trastuzumab pertuzumab]—the CLEOPATRA regimen. But 10 months after diagnosis she has progression in her liver and in her left breast. It’s very disappointing because I’ve gotten very spoiled with that CLEOPATRA regimen to see progression earlier than 18 months.

She then sees her surgeon and is advised that she should have a liver ablation, a complete mastectomy, and continue HP [trastuzumab pertuzumab], which is a little shocking. This is not just a site of oligometastatic disease, but she had diffuse metastases throughout the body. Clearly this isn’t 1 of those cases where cure is going to be possible. We discuss what to do. We go through all the treatment options, and she’s interested in going on to T-DXd [trastuzumab deruxtecan]. Data have just emerged showing great responses, and she receives treatment with T-DXd [trastuzumab deruxtecan]; she has a complete response after 3 cycles.

She tolerates the therapy very well but does have some nausea and significant hair thinning where she had to cut her long hair. It was very noticeable, but she’s does very well with it. The breast mass completely goes away. However, 1 year later her tumor progresses in the lymph nodes and liver. She has no neurological symptoms. We have to change her treatment. The question becomes, would you recommend a brain MRI in a patient who is asymptomatic from a neurological standpoint? There are opportunities for us to chat about this: are you checking an MRI of the brain in patients who are asymptomatic with HER2+ disease?

Joyce A. O’Shaughnessy, MD: We’re going to talk about the DESTINY-Breast03 data in a second. I have less of a reason to do it because T-DXd [trastuzumab deruxtecan] is our second-line choice. We’ll go through those data, but it’s our second-line choice. It’s got good activity in the brain. If somebody has subclinical brain metastases, I’ve got optimism that there’s going to be some good control of those. I don’t feel obligated to do a brain MRI in an asymptomatic patient. This patient is progressing. I’m going to recommend tucatinib, trastuzumab, and capecitabine. I’m going to reserve T-DM1 [trastuzumab emtansine] for her next line after that. I’m going to go on to an excellent brain regimen for her. I don’t feel like I need to make a therapeutic decision.

If she said to me, “I have a history of diarrhea, and I’m not a pill taker, then I have a choice between the tucatinib triplet and T-DM1 [trastuzumab emtansine]. I might get the MRI. My algorithm is going to be second-line T-DXd [trastuzumab deruxtecan], then tucatinib, then T-DM1 [trastuzumab emtansine]. My need for MRIs in asymptomatic women is going to go down. What about you?

Sara A. Hurvitz, MD: That’s an interesting point. I haven’t heard it considered that way. I agree. I wasn’t thinking about it that way when I came in here, but you’re right. How much would it change what we’re going to do? The data for tucatinib were quite compelling, with its intracranial activity, but now we’re seeing compelling data supporting the use of T-DXd [trastuzumab deruxtecan] in this setting. It may become important in that frontline setting when we don’t have a lot of data supporting the intracranial activity of THP [docetaxel, trastuzumab, pertuzumab]. All eyes are on the DESTINY-Breast09 data, that ongoing study of T-DXd [trastuzumab deruxtecan] in the frontline setting. That would make me consider using something different from THP [docetaxel, trastuzumab, pertuzumab] in the frontline setting.

Let’s go to the next slide. This patient insists on having a brain scan. She’s very knowledgeable about HER2+ breast cancer, and she’s a member of many support and advocacy groups. She has an 8-mm lesion in the frontal lobe without any edema. SRS [stereotactic radiosurgery] is recommended. What I considered—you’ve already answered this question—is tucatinib, capecitabine, and trastuzumab. That would be the choice in this patient who has already received T-DXd [trastuzumab deruxtecan] and is now progressing in not only the brain but the liver. If she wasn’t progressing in the liver, and it was an isolated brain metastasis—for example, by a headache prompting a skin—I’d be tempted to do SRS and continue the T-DXd [trastuzumab deruxtecan] because she had such a great response extracranially.

Transcript edited for clarity.