Thomas Bachelot, MD, PhD, a medical oncologist at Centre Leon Berard, discusses therapies available for patients with HER2-positive breast cancer and brain metastases.
It has been shown that the best systemic treatment to control the disease for the longest time and with the best overall survival (OS) improvement will also be the best option for those with brain metastases, according to Bachelot. Subgroup analyses of randomized studies in HER2-positive breast cancer demonstrated the same result in the subgroup of patients who have brain metastases as the ones who do not. This is the case for first line treatment with pertuzumab (Perjeta)/trastuzumab, in the second line with ado-trastuzumab emtansine (T-DM1; Kadcyla), and in the third line with tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine. Because of this, there is no specific treatment for brain metastases.
Bachelot says it is different when a patient has progressive brain metastases because you want to treat those patients with chemotherapy. In this situation, the evidence is less clear, although many treatments have been shown to be able to control brain metastases progression. Most of the time the progression-free survival (PFS) is short, at about 5 months. However, for the triplet combination of tucatinib, trastuzumab, and capecitabine, the HER2CLIMB trial (NCT02614794) had an analysis of patients with brain metastases and showed a PFS of 7 to 9 months.
The HER2CLIMB study was the only one that randomized patients with active brain metastases, and it is the only one that has shown improvement in OS for patients with acute brain metastases. For patients with progressive brain metastases, Bachelot says this treatment regimen is validated with the best evidence.