Patient Case 3: HER2+ Metastatic Breast Cancer With CNS Disease


Following review of the final patient scenario, panelists consider later-line treatment options in the setting of multiply relapsed HER2+ metastatic breast cancer.


Sara Tolaney, MD: We'll turn to our third case, and I’ll pass it to you, Sarah, to take us through this case.

Sarah Sammons, MD: This patient is a 43-year-old female with estrogen receptor negative progesterone receptor negative HER2/3+ on immunohistochemistry. She presented similar to 50% of our new [patients with] metastatic HER2-positive breast cancer in the US these days with de novo metastatic breast cancer. She had palpated a left breast mass that was quite large with axillary lymphadenopathy, so she had systemic staging scans where we, unfortunately, found lung metastasis and bone lesions. She had a lung biopsy, which confirmed the same histologic subtype. It was ER-negative, PR-negative, and HER2+ breast cancer in the lung. She was started on standard of care CLEOPATRA regimen, which is taxane, trastuzumab, and pertuzumab. She had a complete response in the breast, lung, and her bone lesions, which appeared sclerotic. This usually indicates treatment response. After about 6 cycles or so, we continued her on maintenance trastuzumab-pertuzumab. She was ER-negative, so she did not need endocrine therapy. After about 18 months, she had some slow progression in the breast and some clear progression in the lungs. This was before the trastuzumab deruxtecan era, so she received standard-of-care second-line T-DM1 and 7 months later she developed innumerable small brain metastasis.

They were rather symptomatic and unfortunately there were more than 20 lesions. It looked like the lesions in her lungs were progressive as well. She met with radiation oncology. Given the number of lesions in the brain, she underwent whole-brain radiation therapy. At that point, because she had extracranial progression in the lungs and because she had innumerable brain metastasis that were treated, I did want to give her something that would have intracranial and extracranial activity. She was started on the HER2CLIMB tucatinib regimen after whole brain. She had a partial response in the lungs, and the MRI of the brain at her first follow-up scan showed resolution of her enumerable brain mets. She continued doing quite well from a toxicity standpoint on the HER2CLIMB regimen. Then,14 months later she developed some intracranial progression only in a few areas. She had an area in the left cerebellum that had some left meningeal enhancement and then she had some progression in the left frontal and right Sylvian fissures. She was symptomatic due to the cerebellar lesion and her extracranial disease is stable. Radiation oncology was consulted, and they did end up doing another treatment of stereotactic radiosurgery to the cerebellar lesion because it was quite large and it was symptomatic, but the 2 other areas of progression were quite small. They were less than 6 millimeters and probably not symptomatic, so we decided to watch those. At that time, I did recommend transition of her treatment to trastuzumab deruxtecan.

This is for review in a journal right now in a case series, but these are real images. This is her baseline MRI scan. You can see target lesion one in the left cerebellum, target lesion 2 in the left frontal lobe, and target lesion 3 in the right Sylvian fissure. After 3 cycles of T-DXd [trastuzumab deruxtecan], she underwent another staging MRI of her brain. The cerebellar lesion was radiated so we can't say for sure whether T-DXd had activity there, but you could clearly see in target 2 and target 3, at least a partial response. This was really nice, and she was able to continue on T-DXd for some time. She still remains on T-DXd with stable intracranial and extracranial disease after 23 cycles. She did have some grade 2 nausea, which is being managed very well by our team with antiemetics. Additionally, she did have some grade 1 alopecia but is otherwise doing quite well.

Sara Tolaney, MD: That's great to hear that she's continuing to do well and responding to therapy. Could you tell us a little bit about what your thought process was when you chose to utilize T-DXd and what made you choose it at that time?

Sarah Sammons, MD: Before D-B03, we were using trastuzumab deruxtecan or T-DXd in very later lines of therapy. This would've been a more common place where we would've placed T-DXd in the fourth line. I was very excited to use it here because she has already had progression on trastuzumab-pertuzumab, T-DM1, and HER2CLIMB. Our options after that, prior to T-DXd, were fairly slim. It was an easy decision to go to T-DXd. We needed extracranial response which we know T-DXd, even in later lines beyond third line, has more than a 60% response rate. Then in terms of her active brain metastasis, this is an area of investigation that Nancy just talked about. What is T-DXd's activity in active brain mets? We do have several small series, DEBORAH, TUXEDO, and the Duke and Dana Farber collaboration, that are showing intracranial response rates between 45% and 70%, which is excellent for an antibody-drug conjugate. We just have not seen intracranial response rates like that with ADCs before. With that preliminary data, I felt comfortable not radiating those small brain metastasis and just watching them with shorter interval follow-up. It's a good point that I want to ask the experts here. When you choose to watch intracranial lesions and not treat them with radiation, I generally do shorter interval MRI scans, either 6 to 9 months depending on how symptomatic they are. What is your practice?

Nancy Lin, MD: It's the same here, 6 to 9 weeks. So, 2 to 3 cycles depending on how anxious I am about their CNS disease, which depends on the location, the size, and symptomatology, etc.

Transcript edited for clarity.

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