Phase II Trial Finds 24 Gy Preoperative Radiation With Pembrolizumab Boosts T‑Cell Infiltration in HR+/HER2− Breast Cancer

Overview

• TBCRC-053 (P-RAD) randomized 51 node-positive HR+/HER2− patients 1:1:1 to 0 Gy, 9 Gy, or 24 Gy delivered over three days with pembrolizumab before standard neoadjuvant chemotherapy and surgery.
• The share of tumors in the highest quartile of T‑cell infiltration rose with dose to 31% (0 Gy), 40% (9 Gy), and 53% (24 Gy), with statistical significance only at 24 Gy for the primary tumor (P = .023).
• Nodal clearance at surgery trended higher with dose at 24% (0 Gy), 29% (9 Gy), and 33% (24 Gy), and pCR and RCB 0/1 rates generally improved by dose but were not statistically significant due to limited power.
• Exploratory findings showed higher pCR in non‑Luminal A disease vs Luminal A (46.7% vs 6.25%) and in patients with PD‑L1 Q4 expression vs non‑Q4 (50% vs 0%), with a 70% pCR in those with both non‑Luminal A and PD‑L1 Q4.
• Translational analyses indicated increased tertiary lymphoid structures and infiltration by B cells, dendritic cells, immunostimulatory macrophages, and NK cells, supporting an immune‑priming effect and the need for confirmatory trials.