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 (10 mg kg⁻¹ 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.

对程序性死亡配体 1 (PD-L1) 单药抗体作为维持治疗对转移性乳腺癌患者的影响尚不清楚。SAFIR02-BREAST IMMUNO 子研究包括患有人类表皮生长因子受体 2 型 (Her2) 阴性转移性乳腺癌的患者，这些患者在 6 到 8 个化疗周期后疾病没有进展。患者 ( n  = 199) 被随机分配接受 durvalumab（每 2 周 10 mg kg ^-1）或维持化疗。在总体人群中，durvalumab 未改善无进展生存期（调整后的风险比 (HR)：1.40，95% 置信区间 (CI)：1.00-1.96；P  = 0.047）或总生存期（OS；调整后的 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）。^{探索性分析显示，PD-L1 +} TNBC ( n  = 32)患者的死亡 HR 为 0.37 (95% CI: 0.12–1.13)，PD-L1 患者的死亡 HR 为0.49 (95% CI: 0.18–1.34) ^- TNBC ( n  = 29)。在 TNBC 患者中，探索性分析显示，在CD274 增益/扩增（n  = 23）和1.12（95% CI：0.42–2.99；对数秩检验，P = 0.8139) 在 CD274 正常/丢失 ( n  = 32) 的患者中。在探索性分析中，淋巴细胞的肿瘤浸润（CD8、FoxP3 和 CD103 表达）和同源重组缺陷并不能预测对 durvalumab 的敏感性。由于只有一名患者出现生殖系BRCA突变，因此应谨慎解释后一发现。本研究提供了评估单药 durvalumab 在 TNBC 患者维持治疗中的基本原理。探索性分析将 CD274 扩增确定为潜在的敏感性生物标志物。在激素受体阳性和 Her2 阴性疾病的患者中，维持化疗比 durvalumab 更有效。