Concurrent New Systemic Therapies and Radiation Therapy in Breast Cancer: Current Evidence, Future Challenges, and Expert Practice Recommendations for Low- and Middle-Income Countries

PURPOSE The integration of novel systemic therapies including antibody-drug conjugates (ADCs), immune checkpoint inhibitors (ICIs), and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors with radiotherapy (RT) presents new opportunities in breast cancer (BC) management. However, clinical guidance on concurrent administration remains limited, particularly for advanced techniques. MATERIALS AND METHODS A multidisciplinary panel of radiation and medical oncologists from AROME and the Moroccan Medical Oncology Association conducted a literature review and established expert consensus recommendations during the fourth Moroccan Congress of Medical Oncology Private Practice. An evidence-informed, structured consensus process was used to achieve agreement on safety profiles across six RT modalities. RESULTS Trastuzumab deruxtecan has shown a favorable safety profile with whole-breast irradiation and palliative RT, while trastuzumab emtansine combined with stereotactic radiosurgery shows elevated radionecrosis risk. ICIs are generally feasible with most RT modalities and toxicity monitoring applied; however, risk is context dependent, and evidence supporting stereotactic body radiotherapy-ICI benefit in oligometastatic BC remains limited. The use of CDK4/6 inhibitors concurrently with conventional and stereotactic RT seems feasible, although caution is advised for visceral metastases. These experts' agreements are supported by retrospective data and preclinical evidence, highlighting the need for prospective validation. CONCLUSION This expert consensus statement provides pragmatic, modality-specific guidance on combining contemporary RT techniques with selected novel systemic agents in BC, complementing existing European Society for Medical Oncology /European Society for Radiotherapy and Oncology‑oriented frameworks and highlighting areas where prospective data are still needed. The findings underscore the importance of toxicity monitoring, particularly for ADCs in CNS-directed therapies, and call for biomarker-driven studies to optimize combination strategies. These recommendations aim to guide safe integration of novel agents with RT across resource-variable settings, including low- and middle-income countries.