Efficacy and safety of trastuzumab deruxtecan in HER2-positive breast cancer patients with brain metastases after failure of pyrotinib-based therapy

Abstract

Tyrosine kinase inhibitors (TKIs) and trastuzumab deruxtecan (T-DXd) have shown efficacy in HER2-positive patients with brain metastases (BMs). This paper analyzed the efficacy and safety of T-DXd in HER2-positive breast cancer patients with BMs who progressed after pyrotinib treatment. We conducted a single-center, retrospective cohort study. HER2-positive patients with BMs who received T-DXd treatment after disease progression following pyrotinib therapy were identified from electronic medical records. The primary endpoint of this study was central nervous system progression-free survival (CNS-PFS). From April 2021 to July 2023, 15 patients were included in the study. The median CNS-PFS was 7.4 months [95% confidence interval (CI) 6.1–8.8 months], the median PFS for patients with extracranial/total lesions was 6.4 months (95% CI 4.4–8.3 months), and the median OS was 9.8 months (95% CI 5.9–13.8 months). The ORRs for intracranial, extracranial, and overall lesions were 33.3%, 71.4%, and 73.3%, respectively. Adverse events of grade 3 or higher with an incidence rate ≥ 5% included leukopenia (20.0%), neutropenia (13.3%), thrombocytopenia (6.7%), and nausea (6.7%). Adverse events of specific interest, interstitial lung disease or pneumonitis, occurred in 2 patents (13.3%), and both were grade 1. The preliminary data in this study suggest that in clinical practice in China, T-DXd is an optional treatment for patients with active/stable BMs who have progressed on pyrotinib. However, further studies are needed to determine its efficacy and the best treatment sequence for these patients.