Neoadjuvant stereotactic body radiation therapy with durvalumab and oleclumab in ER + HER2 − breast cancer: a randomized phase 2 trial

Patients with estrogen receptor-positive (ER + ), HER2-negative, early breast cancer (BC) have low pathologic complete response (pCR) rates following neoadjuvant chemotherapy. Immune checkpoint inhibitors (ICIs) provide limited benefit in programmed death-ligand 1 (PD-L1)-negative tumors, characterized by an immune-cold tumor microenvironment.

Here we hypothesized that immune-modulating stereotactic body radiation therapy (iSBRT; 3 × 8 Gy) could enhance response through tumor microenvironment reprogramming, and that CD73 blockade could further improve efficacy. We conducted a phase 2, randomized, multicenter trial (Neo-CheckRay) in 147 female patients with high-risk, ER + HER2 − early BC.

Patients received neoadjuvant chemotherapy plus iSBRT alone (No_ICI), with anti-PD-L1 durvalumab (Single_ICI) or with durvalumab plus anti-CD73 oleclumab (Double_ICI). In the intention-to-treat population, the primary endpoint, residual cancer burden 0/1 rate, was 35.4% with No_ICI, 45.1% with Single_ICI and 47.9% with Double_ICI, without statistically significant differences.

pCR rates were 16.7%, 29.4% and 33.3%, respectively ( P = 0.059). In the per-protocol population (MammaPrint High Risk, n = 131), pCR rates were 16.3%, 32.6% and 35.6%, respectively ( P = 0.040).