Concomitant radiation therapy and trastuzumab deruxtecan in metastatic breast cancer: feasibility, safety, and outcomes from a real-life multicentre international cohort

Background and purpose: Radiation therapy (RT) remains a cornerstone of management for metastatic breast cancer (mBC), though systemic therapy drives overall disease control. Administering RT concomitantly with systemic treatment may raise concerns regarding toxicity. This multicentre retrospective study evaluated the safety of trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate, when delivered alongside RT. Materials and methods: Data from six European centres were analysed. Concomitancy was defined as RT administered during T-DXd or within 10 days of a treatment cycle. The primary endpoint was the incidence of grade ≥3 adverse events (AEs). Exploratory endpoints included progression-free survival (PFS) and overall survival (OS). Results: A total of 147 patients were included; 67 received concomitant RT (71 courses) and 80 received T-DXd alone. Median age was 49 years (range 25-85). The central nervous system was the most frequent RT site (54.9 %). Grade ≥3 AEs occurred in 24 patients (16.3 %), with no significant difference between RT and no-RT cohorts (11.9 % vs 20.0 %; p = 0.30). Permanent T-DXd discontinuation due to toxicity occurred in 19 patients (12.9 %), with similar rates in the RT and no-RT groups (11.9 % vs 13.8 %). One case of symptomatic radionecrosis was observed after intracranial RT. Exploratory analyses showed no adverse effect of concomitant RT on PFS or OS. Conclusion: Concomitant administration of T-DXd and RT appears feasible and well tolerated, without increased risk of severe or treatment-limiting toxicity. These real-world findings support the safety of this combination and warrant confirmation in prospective studies.