Role of T-DXd in Patients With HER2+ Metastatic Breast Cancer and CNS Metastasis

Transcript:

Kevin Kalinsky, MD, MS: If I have a patient who has HER2 [human epidermal growth factor receptor 2]–positive breast cancer and a tumor that progressed on tucatinib, I’d use trastuzumab deruxtecan. We have clear data published about the potential and efficacy in this context, in various series of patients. That would be my next go-to. We don’t have great data in terms of sequencing neratinib after tucatinib or even lapatinib-sequencing TKIs [tyrosine kinase inhibitors]. Based on the data that we have in spring 2023, if a patient has a tumor that progressed on tucatinib, I’d probably do trastuzumab deruxtecan next. After that, I’d think about something like neratinib.

We also have chemotherapies that have CNS [central nervous system] penetration. Those include capecitabine, which we’d give in our HER2CLIMB regimen, but also carboplatin-gemcitabine, which has known CNS penetration. Antiestrogen therapy can also keep CNS disease under control. Those are potential options that one could think about in a patient with CNS metastases.

Various studies have demonstrated that there’s CNS activity in patients with HER2+ brain metastases who received T-DXd [trastuzumab deruxtecan]. One of those cohorts is the TUXEDO-1 study, which has demonstrated that there’s CNS activity. We know that there’s systemic control, but it’s been nice to see that there’s CNS activity with this agent as well.

Transcript edited for clarity.