Where are some of the main gaps in our understanding of brain metastases in patients with MBC?
One issue is our understanding of tropism to the brain. In other words, why does MBC spread to the brain? Once we understand this key piece, we can work on developing more effective therapies and therapeutic combinations to block brain metastasis.
For hormone receptor–positive disease, in particular, a central question is whether the current antiestrogen therapies — such as selective estrogen receptor degraders like fulvestrant, as well as targeted AKT inhibitors — have the potential to affect brain tumor activity. The same holds true for TNBC, where antibody drug conjugates and immunotherapies are being evaluated for treatment of brain tumors. For patients with HER2-positive MBC that has spread to the brain, understanding the continued role for tyrosine kinase inhibitors, such as tucatinib and neratinib, as well as whether antibody drug conjugates, including trastuzumab deruxtecan and trastuzumab emtansine, have CNS activity are important areas to explore further.
The CompassHER2 trial, going on now, is randomizing patients with residual HER2-positive disease after neoadjuvant chemotherapy and HER2-targeted therapy to receive trastuzumab emtansine with or without tucatinib. One of the core questions of this study is whether trastuzumab emtansine/tucatinib lowers the rate of brain metastasis and the incidence of systemic metastasis.
Another area in MBC that requires greater scrutiny is patients who develop leptomeningeal disease, which is when cancer cells spread to the cerebrospinal fluid. These patients have a particularly poor prognosis, and it would be helpful to evaluate the efficacy of existing therapies, but these patients are often excluded from clinical trials.
Overall, the ultimate goal in these endeavors is to decrease the rate of metastasis to the brain and improve survival and quality of life in patients with MBC who do experience brain metastases.
A version of this article first appeared on Medscape.com.