Radiotherapy in symptomatic metastatic triple-negative breast cancer treated with first-line pembrolizumab and chemotherapy: A multinational real-world study.

Abstract

e13112 Background: Despite the addition of pembrolizumab to chemotherapy, the prognosis of patients with symptomatic metastatic triple-negative breast cancer (mTNBC) remains poor. We evaluated the indications, toxicity, and outcomes of radiotherapy (RT) added to pembrolizumab and chemotherapy in real-world mTNBC. Methods: This multinational, multicenter retrospective study was conducted within the CEBCC-101 real-world evidence project across 18 cancer centers. Female patients with histologically confirmed mTNBC treated with first-line pembrolizumab plus chemotherapy outside clinical trials in Poland, the Czech Republic, and Slovakia between September 2022 and June 2025 were included. Among 178 eligible patients, 54 received RT. Stereotactic radiotherapy was used in 20 cases. Results: RT was primarily administered for symptomatic disease, most commonly pain, including cases with actual or impending pathological fractures or risk of spinal cord compression. Additional indications included irradiation of progressing sites, superior vena cava syndrome, and bleeding from ulcerated breast tumors. Only two patients received RT for oligometastatic disease. RT sites included bone (n = 20), central nervous system (n = 19), breast/chest wall or regional lymph nodes (n = 10), and other sites (n = 5). Median local control was 14.6 months. RT was generally well tolerated, with acute toxicities reported in 9 patients (16.7%), predominantly grade 1–2, and one grade 3 event. Patients receiving RT had higher rates of hematologic adverse events (67.9% vs 32.1%; p = 0.045) and alopecia (69.8% vs 30.2%; p = 0.029), with no significant differences in chemotherapy dose reductions, treatment delays, or other systemic toxicities. Given the high-risk clinical characteristics of patients requiring RT, progression-free survival (PFS) and overall survival (OS) were significantly shorter in this group. Median PFS was 7.4 months in patients receiving RT versus 8.6 months in those without RT ( p = 0.007), with 12-month PFS rates of 20.3% and 43.5%, respectively. Median OS was 15.6 versus 26.8 months ( p = 0.002), with 24-month OS rates of 22.7% and 56.0%, respectively. Conclusions: Patients with symptomatic mTNBC requiring radiotherapy represent a high-risk population with poor outcomes despite combined pembrolizumab and chemotherapy. While radiotherapy provides effective local control with acceptable toxicity, prospective studies are needed to determine whether greater integration of stereotactic radiotherapy with antibody–drug conjugates can improve outcomes in this setting.