Abstract Background: Triple-negative breast cancer (TNBC) accounts for approximately 15% of invasive breast cancers and is associated with a poor prognosis. The introduction of pembrolizumab in both neoadjuvant and adjuvant settings, as established by the KEYNOTE-522 trial, has improved event free survival and is now considered standard of care. Postoperative adjuvant radiotherapy remains essential in reducing recurrence and mortality. However, combining radiotherapy with pembrolizumab may increase the risk of toxicities, particularly cardiac, and its long-term safety profile remains poorly characterized. This study aims to assess the safety of this combination in TNBC patients. Methods: This monocentric retrospective study, conducted at Institut Curie in Paris, included patients with locally advanced TNBC treated according to the KEYNOTE-522 protocol—neoadjuvant chemotherapy and immunotherapy, followed by surgery and adjuvant therapy including radiotherapy with or without pembrolizumab. Patients were divided into two groups: those receiving concurrent radiotherapy and pembrolizumab (RT-P), and those receiving radiotherapy alone (RT). The primary endpoint was treatment tolerance. Secondary endpoints included overall survival and cancer-specific survival. A p-value 0.05 was considered statistically significant. Results: A total of 89 patients were included, with a median follow-up of 16 months. Forty-one patients received radiotherapy alone, and 48 received concurrent radiotherapy and pembrolizumab. No significant differences were observed between groups in baseline characteristics or overall toxicity, except for grade 1 radiodermatitis, which was more frequent in the RT-P group (83.3% vs. 43.9%). No grade ≥3 toxicities were reported. Two cases of grade 1 pulmonary toxicity occurred in the RT-P group. The mean heart dose was 1.8 Gy range: 0.01-7.9, with no cardiac toxicity attributable to radiotherapy. Conclusion: Adjuvant radiotherapy can be safely administered concurrently with pembrolizumab in TNBC patients without increasing radiation-related adverse events, supporting the continuation of systemic therapy in this high-risk population. Nevertheless, larger prospective studies are needed to assess long-term toxicity. Citation Format: A. EL FAKIH, P. LOAP, L. CABEL, S. ALLALI, K. CAO, M. MIRABEL, J. PIERGA, Y. KIROVA. Real-world safety of concurrent pembrolizumab and radiotherapy in triple-negative breast cancer 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 PS1-07-17.
FAKIH et al. (2026) studied this question.