TPS657 Background: Early-stage triple-negative breast cancer (TNBC) carries a high risk of locoregional recurrence and distant metastasis. The KEYNOTE-522 trial established that adding an immune checkpoint inhibitor to neoadjuvant chemotherapy in high-risk early-stage TNBC yields a pathologic complete response (pCR) rate of 64.8%. However, nearly 40% of patients still fail to achieve pCR. Radiotherapy not only directly eradicates tumor cells but also can induce systemic immunomodulatory effects, such as promoting tumor antigen release and enhancing T-cell infiltration. Therefore, combining radiotherapy with immune checkpoint inhibitors and chemotherapy represents a promising strategy to improve outcomes in early-stage TNBC. Preliminary data from small-sample, single-arm studies suggest that neoadjuvant stereotactic body radiotherapy (SBRT) combined with an anti-PD-L1 antibody and chemotherapy can increase pCR rate to 90%(Liu C., et al., Elife , 2023). However, this therapeutic modality lacks large-scale clinical data to further confirm the radiosensitizing effect of radiotherapy on immune checkpoint inhibitors. This phase III, randomized, controlled, multicenter study aims to evaluate the efficacy and safety of toripalimab (an anti-PD-1 monoclonal antibody) plus chemotherapy with or without SBRT in treatment-naïve TNBC patients. Methods: Eligible patients are treatment-naïve, non-metastatic TNBC with clinical stage cT1cN1-2M0 or cT2N0-2M0 (AJCC 8th edition). Patients are randomized 1:1 to receive toripalimab (240 mg, intravenously, every 3 weeks for 8 cycles) plus nab-paclitaxel (260 mg/m², intravenously, every 3 weeks for cycles 1-4) and carboplatin (AUC=5, intravenously every 3 weeks for cycles 1-4) and epirubicin (90-100 mg/m², intravenously, every 3 weeks for cycles 5-8) and cyclophosphamide (600 mg/m², intravenously every 3 weeks for cycles 5-8), with or without SBRT (8 Gy × 3 fractions). All patients undergo surgery 4-8 weeks after completing neoadjuvant therapy. The primary endpoint is investigator-assessed pCR. Secondary endpoints include breast conservation rate, ipsilateral breast recurrence or locoregional recurrence, overall survival (OS), and safety. Sample size was calculated assuming a pCR rate of 64.8% in the control arm (based on KEYNOTE-522) and 80% in the experimental (SBRT) arm. With a one-sided α of 0.025, 80% power, 1:1 allocation, and accounting for a 20% dropout rate, 159 patients per arm (total N=318) are enrolled. The study was initiated in November 2024. Clinical trial information: NCT06627712 .
Liu et al. (Thu,) studied this question.