Deepak Gupta, Associate Director and Senior Consultant at Medanta Hospital, shared on LinkedIn:
“SBRT with Immunotherapy for ‘Cold’ Breast Tumors.
For years, estrogen receptor-positive (ER+), HER2-negative breast cancer has been tough to crack with immunotherapy – these tumors tend to be ‘immune-cold,’ meaning they don’t respond well to checkpoint inhibitors alone.
The Neo-CheckRay trial (Phase 2, n=147) published in Nature Medicine offers a compelling new strategy.
The Approach
Neoadjuvant chemo + immune-modulating SBRT (3×8 Gy) with or without durvalumab ± oleclumab.
Key Findings
PD-L1-negative tumors showed dramatic benefit:
- Chemo with SBRT alone: 3.4% pCR
- Chemo with SBRT and Durvalumab: 28.1% pCR
- Chemo with SBRT and Dual ICI: 30.0% pCR
Nearly a 9 times improvement in complete response.
SBRT reprograms the tumor microenvironment – paired biopsies confirmed conversion from immune-cold to inflamed phenotype.
Axilla dose matters – keeping nodal dose <1 Gy preserved the ICI benefit.
Adding oleclumab didn’t significantly improve outcomes over anti-PD-L1 alone.
Why This Matters
This is one of the first studies to show that SBRT can ‘wake up’ the immune system in ER+ breast cancer – potentially opening a new treatment paradigm for PD-L1-negative disease.”
Title: Neoadjuvant stereotactic body radiation therapy with durvalumab and oleclumab in ER+HER2− breast cancer: a randomized phase 2 trial
Authors: Alex De Caluwé, Isabelle Desmoulins, Kim Cao, Vincent Remouchamps, Adinda Baten, Eleonore Longton, Karine Peignaux, Andrea Joaquin Garcia, David Venet, Luca Arecco, Elisa Agostinetto, Guilherme Nader-Marta, Zoë Denis, Jennifer Dhont, Paulus Kristanto, Xavier Catteau, Denis Larsimont, Roberto Salgado, Philip Poortmans, John Stagg, Christos Sotiriou, Martine Piccart, Michail Ignatiadis, Emanuela Romano, Laurence Buisseret
You can also read:
Neo-CheckRay: iSBRT and Durvalumab in High-Risk ER+/HER2- Breast Cancer
