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

Immune checkpoint inhibitors (ICIs) provide limited benefit in programmed death-ligand 1 (PD-L1)-negative tumors, characterized by an immune-cold tumor microenvironment.

免疫检查点抑制剂（ICIs）在程序性死亡配体1（PD-L1）阴性肿瘤中的益处有限，这些肿瘤的特点是免疫冷肿瘤微环境。

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.

在这里，我们假设免疫调节立体定向体放射治疗（iSBRT；3 × 8 Gy）可以通过肿瘤微环境重编程来增强反应，并且CD73阻断可以进一步提高疗效。

We conducted a phase 2, randomized, multicenter trial (Neo-CheckRay) in 147 female patients with high-risk, ER+HER2- early BC.

我们进行了一项二期、随机、多中心试验（Neo-CheckRay），在147名高风险、ER+HER2-早期乳腺癌女性患者中进行。

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).

患者接受新辅助化疗加iSBRT单独治疗（No_ICI），或联合抗PD-L1 durvalumab（Single_ICI），或联合durvalumab和抗CD73 oleclumab（Double_ICI）。

In the intention-to-treatpopulation, 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).

在意向治疗人群中，主要终点，即残余癌症负担0/1率，No_ICI组为35.4%，Single_ICI组为45.1%，Double_ICI组为47.9%，差异无统计学意义。pCR率分别为16.7%，29.4%和33.3%（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).

在符合方案人群（MammaPrint高风险，n = 131）中，病理完全缓解（pCR）率分别为16.3%，32.6%和35.6%，差异具有统计学意义（P = 0.040）。

Among PD-L1-negative tumors (n = 91), pCR rates were 3.4%, 28.1% and 30.0%, respectively.

在PD-L1阴性肿瘤（n = 91）中，病理完全缓解（pCR）率分别为3.4%，28.1%和30.0%。

No new safety signals were observed.

未观察到新的安全信号。

Baseline transcriptomic analysis showed low immune signature expression in PD-L1-negative tumors.

基线转录组分析显示PD-L1阴性肿瘤中免疫标志物表达较低。

Paired baseline and on-treatment biopsies obtained 1 week after iSBRT demonstrated tumor microenvironment reprogramming toward an inflamed phenotype in the iSBRT + anti-PD-L1 arms.

在iSBRT治疗后1周获得的配对基线和治疗期间活检显示，iSBRT + anti-PD-L1组的肿瘤微环境向炎症表型重新编程。

These findings suggest that iSBRT + anti-PD-L1 may convert immune-cold ER+HER2- BC into more inflamed tumors and improve response, particularly in PD-L1-negative disease.

这些发现表明，iSBRT + anti-PD-L1可能会将免疫冷的ER+HER2-乳腺癌转变为更具炎症性的肿瘤，并提高反应率，特别是在PD-L1阴性疾病中。

ClinicalTrials.gov registration: NCT03875573 .

ClinicalTrials.gov 注册号：NCT03875573。