A-BRAVE trial: a phase III randomized trial with anti-PD-L1 avelumab in high-risk triple-negative early breast cancer patients.

patients_and_methods

A-BRAVE is a phase III study that randomly assigned patients with high-risk early TNBC to 1 year of avelumab versus observation, after completion of standard surgery and (neo)adjuvant chemotherapy.

A-BRAVE是一项III期研究，随机分配高风险早期TNBC患者在完成标准手术和（新）辅助化疗后，接受avelumab治疗一年或进行观察。

High-risk was defined as either: (i) ≥pN2/any pT, pN1/pT2, or pN0/pT3 after primary surgery (stratum A); or (ii) invasive residual disease (breast and/or nodes) after neoadjuvant chemotherapy (stratum B).

高风险定义为：(i) 初次手术后≥pN2/任何pT，pN1/pT2，或pN0/pT3（A层）；或(ii) 新辅助化疗后乳腺和/或淋巴结有侵袭性残留病灶（B层）。

Coprimary endpoints were disease-free survival (DFS) in the intention-to-treat(ITT) and stratum B populations.

共同主要终点是在意向治疗（ITT）人群和B层人群中无病生存（DFS）。

Secondary endpoints were overall survival(OS) and DFS in PD-L1-positive patients.

次要终点包括PD-L1阳性患者的总生存（OS）和无病生存（DFS）

PD-L1 was evaluated in treatment-naïve tumor samples by immunohistochemistry (73-10 RUO assay, Agilent Technologies) and digital pathology.

通过免疫组化（73-10 RUO试剂盒，安捷伦科技）和数字病理学评估了治疗前肿瘤样本中的PD-L1表达

Results

From June 2016 to October 2020, 466 patients were randomly assigned: 383 entered stratum B (82%) and 83 entered stratum A (18%).

从2016年6月到2020年10月，共有466名患者被随机分配：383名进入B层（占82%），83名进入A层（占18%）。

At a median follow-up of 52.1 months, avelumab did not significantly improve DFS in the ITT population [hazard ratio(HR) 0.81, 95% confidence interval(CI) 0.61-1.09, P = 0.172; 3-year DFS estimates were 68.3% for avelumab versus 63.2%], or in stratum B (HR 0.80, 95% CI 0.58-1.10, P = 0.170; 3-year DFS estimates were 66.9% for avelumab versus 60.7%).

在中位随访52.1个月时，avelumab在ITT人群中并未显著改善无病生存期（DFS）[风险比（HR）0.81，95%置信区间（CI）0.61-1.09，P = 0.172；avelumab的3年DFS估计为68.3%，而对照组为63.2%]，在B层中也是如此（HR 0.80，95% CI 0.58-1.10，P = 0.170；avelumab的3年DFS估计为66.9%，而对照组为60.7%）。

In a descriptive analysis, avelumab reduced the hazard of OS events: HR 0.66, 95% CI 0.45-0.97.

在描述性分析中，avelumab 降低了总生存事件的风险：风险比为0.66，95%置信区间为0.45-0.97。

The 3-year OS estimates for avelumab and control arm were 84.8% (95% CI 79.5% to 88.8%) and 76.3% (95% CI 70.1% to 81.3%), respectively.

avelumab组和对照组的3年总生存估计分别为84.8%（95%置信区间79.5%至88.8%）和76.3%（95%置信区间70.1%至81.3%）。

PD-L1 status was prognostic but not predictive for avelumab benefit in terms of DFS (test for interaction P = 0.155).

PD-L1状态对于avelumab在无病生存期（DFS）上的益处具有预后意义，但不具有预测意义（交互作用检验P = 0.155）。

Conclusions

For patients with TNBC at high risk of relapse who complete standard treatment with surgery and (neo)adjuvant chemotherapy, 1 year of adjuvant avelumab versus observation did not improve DFS.

对于完成手术和（新）辅助化疗标准治疗的高复发风险三阴性乳腺癌（TNBC）患者，与观察组相比，1年的avelumab辅助治疗并未改善无病生存期（DFS）。

However, a descriptive analysis suggests a potential favorable impact on OS.

然而，描述性分析表明对总生存期可能有潜在的有利影响。