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

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-08-28 DOI:10.1016/j.annonc.2025.08.005

P F Conte, M V Dieci, G Bisagni, P Schmid, A Zambelli, F Piacentini, M De Laurentiis, A G Favaretto, S Tamberi, G V Bianchi, C Zamagni, S Cinieri, D C Corsi, L Del Mastro, A Ferro, A Gennari, M Mion, A Musolino, L Nicolé, P Del Bianco, G L De Salvo, V Guarneri

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引用次数: 0

Abstract

Background: The A-BRAVE trial evaluated the efficacy of avelumab, an anti-programmed death-ligand 1 (PD-L1) antibody, as adjuvant treatment of patients with early triple-negative breast cancer (TNBC) at high risk.

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. 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). Coprimary endpoints were disease-free survival (DFS) in the intention-to-treat (ITT) and stratum B populations. Secondary endpoints were overall survival (OS) and DFS in PD-L1-positive patients. PD-L1 was evaluated in treatment-naïve tumor samples by immunohistochemistry (73-10 RUO assay, Agilent Technologies) and digital pathology.

Results: From June 2016 to October 2020, 466 patients were randomly assigned: 383 entered stratum B (82%) and 83 entered stratum A (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%). In a descriptive analysis, avelumab reduced the hazard of OS events: HR 0.66, 95% CI 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. PD-L1 status was prognostic but not predictive for avelumab benefit in terms of DFS (test for interaction 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. However, a descriptive analysis suggests a potential favorable impact on OS.

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a - brave试验：抗pd - l1 avelumab在高危三阴性早期乳腺癌患者中的3期随机试验。

背景：A-BRAVE试验评估了抗PD-L1抗体avelumab作为高危早期三阴性乳腺癌（TNBC）患者辅助治疗的疗效。患者和方法：a - brave是一项III期研究，在完成标准手术和新辅助/辅助化疗后，将高危早期TNBC患者随机分为1年avelumab和观察组。高危定义为：1)原发性手术后pN2/任何pT、pN1/pT2或pN0/pT3 （A层）；或2)新辅助化疗后侵袭性残留疾病（乳房和/或淋巴结）（B层）。共同主要终点是意向治疗（ITT）和B层人群的无病生存（DFS）。次要终点是pd - l1阳性患者的总生存期（OS）和DFS。通过免疫组织化学（73-10 RUO测定，Agilent Technologies）和数字病理学评估治疗初期肿瘤样本中的PD-L1。结果：2016年6月至2020年10月，随机抽取466例患者，其中383例进入B层（82%），83例进入A层（18%）。在52.1个月的中位随访中，avelumab并没有显著改善ITT人群的DFS (HR 0.81, 95% CI 0.61-1.09, p=0.172； avelumab的3年DFS估计值为68.3%对63.2%)，或在B层（HR 0.80, 95% CI 0.58-1.10, p=0.170； avelumab的3年DFS估计值为66.9%对60.7%）。在一项描述性分析中，avelumab降低了OS事件的风险：HR 0.66, 95% CI: 0.45-0.97。avelumab组和对照组的3年OS估计分别为84.8% （95% CI: 79.5-88.8）和76.3% （95% CI: 70.1-81.3）。PD-L1状态对预后有影响，但不能预测avelumab的DFS获益（相互作用检验p=0.155）。结论：对于完成手术和新辅助/辅助化疗的标准治疗的高危复发TNBC患者，1年的辅助avelumab与观察相比并没有改善DFS。然而，描述性分析表明对操作系统的潜在有利影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.