Managing HER2+ Breast Cancer With Leptomeningeal Metastases


Panelists center their discussion on the challenges inherent in managing leptomeningeal metastases in patients with HER2+ breast cancer.


Sara Tolaney, MD:This patient also had leptomeningeal disease. How common is that, Nancy? How often do you see this? In terms of treatment approaches, what do you think if you see someone with leptomeningeal enhancement on imaging?

Nancy Lin, MD: We don’t have firm estimates about the incidence of leptomeningeal disease. You can’t get that from SEER [Surveillance Epidemiology and End Results program] because it looks only at sights for first metastases; leptomeningeal disease is later on. You have to look at single-institution series, and it’s like a very fake meta-analysis in one’s head. We quote about a 5% risk in the setting of metastatic HER2 [human epidermal growth factor receptor 2]–positive breast cancer. The other groups at risk are patients with triple-negative disease and lobular breast tumors ...

At our institution [Dana-Farber Cancer Institute], we found that BRCA carriers, which look like BRCA1 and BRCA2 mutation status, is also associated with the development of CNS [central nervous system] disease, including leptomeningeal disease. In terms of treatment options for patients with HER2+ breast cancer, the HER2CLIMB regimen has been looked at within a clinical trial. Ada is going to talk more about that. Additionally, Dr [Sarah] Sammons and I have collaborated on a case series with a T-DXd [trastuzumab deruxtecan]. This shows some interesting results in patients with leptomeningeal disease. There are some options.

Two phase 2 experiences were just published in Neuro-Oncology describing the role of intrathecal trastuzumab, which looks very safe. No maximum tolerated dose was identified, and in both studies the dose went to the maximum level. There was an activity seen with improvement on survival compared with historical control, so at least there’s a little [more information]. It’s not a lot but, there’s a little progress there. We have some systemic options to offer patients in addition to the usual radiation types of options that we’ve historically offered.

Sara Tolaney, MD:It’s great to see progress. Nancy mentioned that with HER2CLIMB, there’s a little data for how that regimen works in patients with leptomeningeal disease. Ada, we’d love to hear about that.

Adrienne Waks, MD: There are a lot of challenges in treating patients with leptomeningeal disease. It’s very treatment refractory, but 1 of the separate challenges is that we don’t have a lot of dedicated data to help us guide patients with leptomeningeal disease, in terms of what they should be receiving and what they might be benefiting from. There was a small but important cohort published looking specifically at patients with leptomeningeal disease who were treated with the HER2CLIMB regimen, tucatinib, trastuzumab, and capecitabine. The data looked promising. It was a single-arm trial, and it was not a randomized trial, so we didn’t have anything to compare it with other than historical controls. But in this reasonably small cohort of patients, there was an overall survival of about 10 months. This compares favorably with historical controls, which is a few months of overall survival after a diagnosis of leptomeningeal disease. That looks promising. This investigator did something interesting, looking in the CSF [cerebrospinal fluid] to see if tucatinib was present there. They showed that it was. They were able to demonstrate that tucatinib was present in the CSF of those patients, which is something that not a lot of trials and groups have looked at. Those data were a good starting point. We could benefit from a lot more robust data ... but this was an exciting preliminary trial.

Sara Tolaney, MD:Very impressive. It’s not easy to do that kind of trial.

Adrienne Waks, MD: No.

Sara Tolaney, MD:It’s nice to have those data available.

Transcript edited for clarity.

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