Gaps in Treatment for HER2+ MBC With Brain Metastasis

Lisa A. Carey, MD, FASCO: Let’s address the unmet needs and some of the ways we’ll move forward. Lee, do you want to comment on the HER2CLIMB trial and the prevention of early initiation? These aren’t known things, but they’re future directions.

Lee S. Schwartzberg, MD, FACP: Right. One of the exploratory analyses in HER2CLIMB looking at patients who developed new brain lesions over time. This was reported recently, and it basically showed that the patients who received tucatinib [Tukysa] had an improvement in not developing a new brain lesion, and the median hasn’t been reached. This is across the entire population. They haven’t looked at the subset group who had brain metastases, which was 50% of the population. But across the entire 600-patient population, the median time to develop new brain metastases was informative, that was about 12 months, across the entire group. We see that about half the population had brain metastases and the other half didn’t. But we’re seeing new brain metastases occurring in that population, and tucatinib seems to have, in this exploratory analysis, a benefit in reducing new brain metastases from forming.

Lisa A. Carey, MD, FASCO: That bodes well for the CompassHER2 trial in the adjuvant residual disease setting. The TBCRC 049 study was presented by Erica Stringer-Reasor recently, which is looking at doing PK [pharmacokinetics] in CSF [cerebrospinal fluid]. What do you think about that?

Lee S. Schwartzberg, MD, FACP: From an experimental point of view, I think it will give us translational information on how well these drugs are working. I know we’re going to talk about leptomeningeal disease, but in my own practice [West Cancer Center & Research Institute in Memphis, Tennessee], it seemed like years ago that we had a lot of that, then we didn’t have it, and now we’re seeing it again because we’re controlling everything else better. It’s an interesting approach to understand where we get these high concentrations that are going to be cytotoxic with tucatinib, other drugs, and the ADCs [antibody-drug conjugates].

Reshma Mahtani, DO: That supports what we’re seeing in the HER2CLIMB study. It’s an active agent in the brain: the drug and its predominant metabolite get in.

Lisa A. Carey, MD, FASCO: That study is in leptomeningeal disease, which is still a challenge. The only thing I’d add—I can’t remember who made the point earlier—is that we don’t have much resection of brain metastases anymore. A couple of years ago, Priscilla Brastianos showed that if you do DNA profiling in brain metastases, the actionability profile may differ. We may be throwing out the baby with the bathwater by not using these things to histologically confirm what we’re looking at, if it’s the first site. We also may be losing some informative data, regarding actionability, for some of these brain metastases-dominant patients. We may be circling back to asking and getting neurosurgeons more involved in the future.

Transcript Edited for Clarity