Yan Xiao, Lv Qi, Wu Jiangzhuo, Fang Jiang, Peng Lin, Zhao Xiaobo
Department of Thyroid and Breast Surgery/School of Clinical Medicine, North Sichuan Medical College/Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
Department of Surgical Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
Front Oncol. 2025 Aug 7;15:1635418. doi: 10.3389/fonc.2025.1635418. eCollection 2025.
BACKGROUND: The efficacy and immune-mediated safety of PD-1/PD-L1 inhibitors in triple-negative breast cancer (TNBC) remain controversial. Given TNBC's aggressive biology and poor prognosis, definitive evidence is urgently needed. We performed this meta-analysis to comprehensively assess the benefits and safety of these inhibitors by examining clinical trial data for TNBC. METHODS: Up until October 25, 2024, a thorough search was done in the PubMed, Embase, and Cochrane databases to find research assessing PD-1/PD-L1 inhibitors in treating TNBC. This study ultimately included 8 randomized controlled trials involving 5,512 patients. Pathological complete response (pCR), progression-free survival (PFS), overall survival (OS), event-free survival (EFS), and immune-related adverse events (irAEs) were among the primary objectives, which defined as adverse drug reactions affecting various organ systems due to immune system activation, were graded according to CTCAE v5.0 criteria. RESULTS: The combination of PD-1/PD-L1 inhibitors with neoadjuvant chemotherapy significantly increased pCR rates by 77% compared to chemotherapy alone (OR=1.77, 95% CI: 1.28-2.45, P<0.01). Subgroup analyses indicated that the benefit of pCR was more evident in patients with lymph node positivity(OR=2.57,95% CI:1.76-3.75, P < 0.01). For EFS, the integration of immune checkpoint inhibitors(ICIs) combination therapy decreased the possibility of events by 35% (HR=0.65,95%CI:0.54-0.80, P< 0.01), with notable benefits observed in earlier-stage (T1-T2) patients(HR= 0.53, 95%CI:0.40-0.70, P < 0.01). Similarly, PFS was improved in the experimental group for both ITT (HR=0.79,95% CI, 0.71-0.88, P<0.01) and PD-L1 positive populations (HR=0.71,95%CI:0.63-0.81, P < 0.01). However, the incidence of irAEs was significantly higher in the ICIs group compared to the neoadjuvant chemotherapy group (OR=2.77,95% CI:1.93-3.96, P < 0.01). CONCLUSION: With lymph node status acting as a crucial predictor, the combination of PD-1/PD-L1 inhibitors and neoadjuvant chemotherapy dramatically improves pCR and EFS in TNBC. Additionally, it improves OS and PFS, although at the cost of an increased incidence of irAEs. These findings offer insightful information for upcoming clinical trial designs, economic evaluations, and clinical decision-making in TNBC treatment. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42025640551.
背景：PD-1/PD-L1抑制剂在三阴性乳腺癌（TNBC）中的疗效和免疫介导的安全性仍存在争议。鉴于TNBC侵袭性生物学行为和不良预后，迫切需要确凿证据。我们进行了这项荟萃分析，通过审查TNBC的临床试验数据来全面评估这些抑制剂的益处和安全性。 方法：截至2024年10月25日，在PubMed、Embase和Cochrane数据库中进行了全面检索，以查找评估PD-1/PD-L1抑制剂治疗TNBC的研究。本研究最终纳入了8项随机对照试验，涉及5512例患者。主要指标包括病理完全缓解（pCR）、无进展生存期（PFS）、总生存期（OS）、无事件生存期（EFS）以及免疫相关不良事件（irAEs），后者定义为由于免疫系统激活而影响各个器官系统的药物不良反应，并根据CTCAE v5.0标准进行分级。 结果：与单纯化疗相比，PD-1/PD-L1抑制剂与新辅助化疗联合使用显著提高了pCR率，提高了77%（OR=1.77，95%CI：1.28 - 2.45，P<0.01）。亚组分析表明，pCR的益处在淋巴结阳性患者中更为明显（OR=2.57，95%CI：1.76 - 3.75，P<0.01）。对于EFS，免疫检查点抑制剂（ICIs）联合治疗降低了35%的事件发生可能性（HR=0.65，95%CI：0.54 - 0.80，P<0.01），在早期（T1 - T2）患者中观察到显著益处（HR=0.53，95%CI：0.40 - 0.70，P<0.01）。同样，在ITT人群（HR=0.79，95%CI，0.71 - 0.88，P<0.01）和PD-L1阳性人群（HR=0.71，95%CI：0.63 - 0.81，P<0.01）中，试验组的PFS均得到改善。然而，ICIs组的irAEs发生率显著高于新辅助化疗组（OR=2.77，95%CI：1.93 - 3.96，P<0.01）。 结论：以淋巴结状态作为关键预测指标，PD-1/PD-L1抑制剂与新辅助化疗联合使用可显著改善TNBC的pCR和EFS。此外，它还改善了OS和PFS，尽管代价是irAEs发生率增加。这些发现为TNBC治疗中即将进行的临床试验设计、经济评估和临床决策提供了有见地的信息。 系统评价注册：https://www.crd.york.ac.uk/prospero/，标识符CRD42025640551。
Cochrane Database Syst Rev. 2018-2-6
Signal Transduct Target Ther. 2025-2-19
N Engl J Med. 2024-11-28
Zotero 插件
