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Top Line: What is the intracranial response rate for trastuzumab deruxtecan (T-DXd)?\

The Study: T-DXd plays an important role in the management of advanced HER2+ (and now HER2-low) breast cancer. While we have seen that small molecule HER2 drugs are effective for patients with brain metastases (BM), T-DXd is a larger molecule and its intracranial activity is less certain. DEBBRAH is a phase II trial assessing the intracranial activity of T-DXd in HER2+ and HER2-low breast cancer. This report focuses on three cohorts of patients with HER2+ breast cancer (not the HER2-low group) and either non-progressing BM after local therapy, asymptomatic but untreated BM, and progressing BM after local therapy. Numbers were small with just 8, 4, and 9 patients in each cohort, respectively. At 4 months the response rate was 50% among those with untreated BM and 44.4% among those progressing after local therapy. All responses were partial with no complete responses. There were no major neurological toxicity events. How do these compare with other HER2 targeted agents? Well, at 21 patients total, we can’t really make head to head comparisons with much larger trials such as HER2CLIMB. Nonetheless, the response rates seem encouraging and support the notion that T-DXd has some degree of intracranial activity.

TBL: In this small study, T-DXd showed intracranial activity in patients with HER2+ breast cancer. | Perez-Garcia, Neuro Oncol 2022