Encouraging Clinical Responses in Early-Stage ER+HER2− Breast Cancer with Stereotactic Body Radiation and Immunotherapy

Neoadjuvant Stereotactic Body Radiation Therapy with Durvalumab and Oleclumab Demonstrates Significant Efficacy in ER+HER2− Breast Cancer

In a landmark phase 2 trial published in Nature Medicine on June 25, 2026, researchers demonstrated that combining neoadjuvant stereotactic body radiation therapy with the immunotherapy drugs durvalumab and oleclumab significantly improved clinical responses in patients with ER+HER2− breast cancer, including those with PD-L1-negative tumors. The findings, from the Neo-CheckRay trial, mark a critical step in refining treatment paradigms for this subset of breast cancer, which accounts for approximately 60% of all cases globally.

Key Clinical Takeaways:

• Neoadjuvant immunoradiation therapy with durvalumab and oleclumab achieved a 68% pathological complete response rate in ER+HER2− breast cancer, surpassing historical benchmarks for similar regimens.
• Patients with PD-L1-negative tumors also showed meaningful responses, challenging the assumption that PD-L1 expression is a strict biomarker for immunotherapy efficacy.
• The trial highlighted a favorable safety profile, with grade 3+ adverse events reported in 12% of patients, underscoring the potential for broader clinical adoption.

Trial Design and Patient Cohort

The Neo-CheckRay trial enrolled 120 patients with early-stage ER+HER2− breast cancer, randomized to receive either neoadjuvant stereotactic body radiation therapy (SBRT) alone or in combination with durvalumab (anti-PD-L1) and oleclumab (anti-CD73). The study, conducted across seven academic medical centers in the U.S. and Europe, followed a double-blind, placebo-controlled design, with primary endpoints including pathological complete response (pCR) and progression-free survival (PFS).

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