eligibility_summary
Eligible: adults (>=18) with unresectable/metastatic HER2-low breast cancer (IHC 1+ or IHC 2+/ISH-), previously treated with metastatic chemo or relapsed during or within 6 months after adjuvant chemo, starting T-DXd or physicians-choice chemo per SmPC, with consent. Exclude: pregnancy/breastfeeding or participation in a still-blinded interventional study. No other specific exclusions, treatment per SmPC.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05945732 (DESTINY-Breast Respond HER2-low Europe) is an observational study of trastuzumab deruxtecan (T-DXd, Enhertu), an antibody–drug conjugate: a humanized anti-HER2 IgG1 (trastuzumab) linked to a topoisomerase I inhibitor payload (DXd). Mechanism: binds HER2 on tumor cells (HER2-low: IHC 1+ or 2+/ISH−), is internalized, releases DXd to inhibit topo I and cause DNA damage/apoptosis, the antibody can mediate ADCC, and the membrane-permeable payload enables a bystander effect. A registry arm captures conventional chemotherapies: capecitabine (antimetabolite, 5-FU prodrug, thymidylate synthase inhibition), gemcitabine (nucleoside analog, DNA synthesis blockade), eribulin (microtubule inhibitor, suppresses polymerization), paclitaxel/nab-paclitaxel (taxanes, microtubule stabilization). Targeted cells/pathways: HER2/ERBB2-positive tumor cells, topoisomerase I, DNA replication, thymidylate synthase, and microtubule dynamics.