Abstract Background Antibody-drug conjugates (ADCs) have become an integral part of systemic therapy for breast cancer. As radiation therapy (RT) continues to play a central role in the management of breast cancer, the safety of combining ADCs with RT has become an emerging area of clinical interest. However, there remains limited data regarding the safety of ADCs administered concurrently with extracranial RT. This study aims to assess real-world data on the safety of combining ADCs with extracranial RT. Method A retrospective chart review of patients who received concurrent ADC therapy (trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), and trastuzumab deruxtecan (T-DXd)) and extracranial RT at a single academic institution was conducted. RT was delivered to the breast and/or chest wall with or without regional nodal irradiation (RNI). Demographic, clinical, and treatment data as well as adverse events were extracted from the electronic medical record. Concurrent therapy was defined as ADC administration within 4 weeks before or after the start of RT. Results A total of 49 patients who received extracranial RT in conjunction with ADCs were included in this retrospective analysis. Average months of follow up for the patients was 22 months after receiving RT. The median age of patients was 54 (range 30-76) at the time of RT. A majority patients were stage 0-2 (n=32, 65%), HR+ (n=35, 71%), HER2+ (n=40, 82%), post-menopausal (n=31, 63%), and received T-DM1 (n=43, 88%). Four patients received SG and two patients received T-DXd. The most common site treated was the chest wall with regional nodal irradiation (n=26, 53%) with 50 Gy in 25 fractions (n=34, 69%). The most frequently reported side effects were grade 1-2 skin dermatitis which was reported in 36 patients (73%), and fatigue in 22 patients (45%). Three patients had grade 3 dermatitis and one had grade 1 esophagitis. Importantly, no radiation courses were discontinued due to adverse effects. Conclusion In our study of concurrent use of ADCs with RT to breast and/or chest wall +/- RNI, no unexpected toxicities occurred. This study adds to real-world evidence that extracranial radiation therapy can be safely administered alongside ADCs. Citation Format: A. Basta, A. Klug, G. Ni, L. Wajahat, W. Alhassani, M. Awad, V. Khatri, R. Costa, M. Mills, I. Washington, R. Diaz, K. Ahmed. Utilization and safety of concurrent antibody drug conjugates alongside extracranial radiation therapy in the real-world setting abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-05-09.
Basta et al. (Tue,) studied this question.