SAFIR02-BREAST IMMUNO研究包涵了人类表皮生长因子受体2（Her2）阴性转移性乳腺癌患者，这些患者在经过6至8个化疗周期后仍未取得进展。这些患者（n = 199）被随机分为durvalumab（每2周10 mg mg-1）治疗组或维持化疗组。在总人群中，durvalumab并不能改善无进展生存期（优化后风险比率（HR）：1.40，95％置信区间（CI）：1.00-1.96；P = 0.047）或整体生存率（OS；优化后HR：0.84， 95％CI：0.54-1.29；P = 0.423）。

在一项探索性亚组分析中，durvalumab改善了三阴性乳腺癌患者的OS（TNBC；n = 82； HR：0.54，95％CI：0.30-0.97，P = 0.0377）。探索性分析表明，程序性死亡配体1（PD-L1） + TNBC（n = 32）患者的死亡HR为0.37（95％CI：0.12-1.13），PD-L1- TNBC患者为0.49（95％CI：0.18-1.34） （n = 29）。

对于TNBC患者的探索性分析显示，durvalumab对CD274增益/扩增（n = 23）患者的功效（OS）HR为0.18（95％CI：0.05–0.71; log-rank test，P = 0.0059）。CD274正常/缺失（n = 32）患者的HR 为1.12（95％CI：0.42-2.99；对数秩检验，P = 0.8139）。淋巴细胞（CD8、FoxP3和CD103表达）浸润肿瘤和同源重组缺失不能预测患者对durvalumab的敏感性。由于只有一名患者出现种系BRCA突变，因此应谨慎解释这一发现。

本研究为评估TNBC患者单药durvalumab治疗提供了依据。探索性分析确定CD274扩增是durvalumab敏感的潜在生物标志物。而在雌激素受体阳性和Her2阴性患者中，维持化疗比durvalumab更有效。

研究人员表示，在转移性乳腺癌患者中尚不清楚靶向PD-L1单药抗体的功效。

附：英文原文

Title: Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial

Author: Thomas Bachelot, Thomas Filleron, Ivan Bieche, Monica Arnedos, Mario Campone, Florence Dalenc, Florence Coussy, Marie-Paule Sablin, Marc Debled, Claudia Lefeuvre-Plesse, Anthony Goncalves, Marie-Ange Mouret Reynier, William Jacot, Benoit You, Philippe Barthelemy, Benjamin Verret, Nicolas Isambert, Xavier Tchiknavorian, Christelle Levy, Jean-Christophe Thery, Tifenn LHaridon, Jean-Marc Ferrero, Alice Mege, Francesco Del Piano, Etienne Rouleau, Alicia Tran-Dien, Julien Adam, Amelie Lusque, Marta Jimenez, Alexandra Jacquet, Ingrid Garberis, Fabrice Andre

Issue&Volume: 2021-01-18

Abstract: The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did not progress after six to eight cycles of chemotherapy. Patients (n=199) were randomized to either durvalumab (10mg kg1 every 2 weeks) or maintenance chemotherapy. In the overall population, durvalumab did not improve progression-free survival (adjusted hazard ratio (HR): 1.40, 95% confidence interval (CI): 1.00–1.96; P=0.047) or overall survival (OS; adjusted HR: 0.84, 95% CI: 0.54–1.29; P=0.423). In an exploratory subgroup analysis, durvalumab improved OS in patients with triple-negative breast cancer (TNBC; n=82; HR: 0.54, 95% CI: 0.30–0.97, P=0.0377). Exploratory analysis showed that the HR of death was 0.37 (95% CI: 0.12–1.13) for patients with PD-L1+ TNBC (n=32) and 0.49 (95% CI: 0.18–1.34) for those with PD-L1 TNBC (n=29). In patients with TNBC, exploratory analyses showed that the HR for durvalumab efficacy (OS) was 0.18 (95% CI: 0.05–0.71; log-rank test, P=0.0059) in patients with CD274 gain/amplification (n=23) and 1.12 (95% CI: 0.42–2.99; log-rank test, P=0.8139) in patients with CD274 normal/loss (n=32). Tumor infiltration by lymphocytes (CD8, FoxP3 and CD103 expressions) and homologous recombination deficiency did not predict sensitivity to durvalumab in exploratory analyses. This latter finding should be interpreted with caution since only one patient presented a germline BRCA mutation. The present study provides a rationale to evaluate single-agent durvalumab in maintenance therapy in patients with TNBC. Exploratory analyses identified CD274 amplification as a potential biomarker of sensitivity. Maintenance chemotherapy was more effective than durvalumab in patients with hormone receptor-positive and Her2-negative disease.

DOI: 10.1038/s41591-020-01189-2

Source: https://www.nature.com/articles/s41591-020-01189-2