HER2+ Breast Cancer With CNS or Leptomeningeal Metastases: Future Directions in Care


Closing out his review of therapy for HER2+ metastatic breast cancer, Kevin Kalinsky, MD, MS, looks toward future evolutions in the treatment landscape.


Kevin Kalinsky, MD, MS: One major issue in HER2 [human epidermal growth factor receptor 2]–positive disease is CNS [central nervous system] metastases; that rate is about 50%. Of a subset of those, we can see patients with leptomeningeal disease. This is a challenging disease regardless of the subtype of breast cancer, whether it’s triple negative, ER [estrogen receptor] positive, or HER2+. Leptomeningeal disease can present in very odd ways, so it’s 1 thing to be mindful of a patient complaining of weird pain or weird CNS adverse effects. It’s a devastating disease. We have data about the potential activity of tucatinib in the context of patients with leptomeningeal disease. If I have a patient with HER2+ disease, that’s my preferred regimen. But if a patient had a tumor that progressed on that regimen, I’d think about trastuzumab deruxtecan in this context as well, even though there are more limited data for that subset of patients.

There are a lot of exciting opportunities for development in the context of HER2+ disease; we’ve made real advances. There’s no question that that has happened in patients in the early stage and metastatic settings. There are other HER2 agents in development—other antibody-drug conjugates and other immunotherapies, including CAR [chimeric antigen receptor] T cells. There are ongoing studies looking at this in HER2+ disease, and these drugs are coming so fast that we have to catch up to the data and figure out how best to sequence.

There’s potential that trastuzumab deruxtecan and tucatinib will move up in the metastatic setting, where we may think about using those drugs earlier in the residual disease setting, for patients who had neoadjuvant therapy. There’s a study for patients with residual disease called the CompassHER2 RD study, which compares residual disease and T-DM1 [trastuzumab emtansine] plus or minus tucatinib. There’s also a study that’s ongoing, DESTINY-Breast03, that compares T-DM1 [trastuzumab emtansine] vs trastuzumab deruxtecan. There’s no reason to think that those agents, when used in that setting, won’t build upon the efficacy that we’re seeing in the treatment of residual disease. We’ll have to see what the toxicity profile looks like in that population but also whether there’s a decrease in the rate of CNS metastases. Our goal is not just for the treatment of patients who have CNS disease but also to prevent CNS disease from happening.

Hopefully this was a well-rounded and detailed patient-based conversation about how we think about treating patients with HER2+ disease. I appreciate you joining me. I hope you have found this OncLive® My Treatment Approach program to be useful and valuable to the management of your patients with metastatic disease, particularly those who have HER2+ metastatic breast cancer. Thank you for your attention.

Transcript edited for clarity.

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