Would you use T-DXd or capecitabine/trastuzumab/tucatinib for HER2+ metastatic breast cancer with predominantly CNS progression after THP?  

We now have long-term overall survival data from the DESTINY-Breast03 (DB03) trial, which further supports the efficacy of trastuzumab deruxtecan (T-DXd) in patients with HER2+ metastatic breast cancer, including those with CNS metastases. However, my preference remains unchanged, favoring the HER2C...

Clinical trials with T-DXd and capecitabine/tucatinib/trastuzumab have included patients with brain metastases and have reported on intracranial responses in patients with brain metastases. It is important to note that measuring brain metastases can be difficult and there is some variability in resp...

For patients who have received Trastuzumab and Pertuzumab-based therapy and experience brain progression, we have different options. These patients were excluded in both DESTINY-BREAST03 and HER2CLIMB trials. In the first case because patients with unstable metastasis were not allowed to be included...

Either would be very reasonable and are FDA-approved in that 2nd line setting. The CNS data is very compelling for the HER2CLIMB regimen and is good randomized data with active and untreated CNS mets. But many CNS-specific studies have now shown response rates of upwards of 70% in brain mets with T-...

In practice, I personalize this decision to the individual patient. Both regimens are reasonable options with the current available data, and they have not yet been compared head-to-head. Additionally, each regimen appears to have activity after the use of the other one. I base my decision on comorb...