目的： 系统评价单药程序性死亡受体1 （PD-1）抑制剂对比化疗二线治疗晚期食管鳞状细胞癌（ESCC）患者的疗效及安全性，以期为临床决策提供最佳循证医学证据。 方法： 计算机检索The Cochrane Library、Web of Science、PubMed、EMbase、CNKI和万方等数据库，同时检索J Clin Oncol 、 N England Oncol 、 Lancet Oncol等杂志以及ASCO、EMSO会议摘要中有关单药PD-1抑制剂对比传统化疗二线治疗晚期ESCC患者的临床随机对照试验（RCT），筛选文献，提取资料，采用RevMan5.3进行Meta分析。 结果： 共纳入5项RCT研究（1 732例患者）。与化疗组比，单药PD-1抑制剂二线治疗晚期ESCC可显著延长患者的总生存期（OS） （HR＝0.75，95% CI：0.67~0.83，P<0.000 01）。以 PD-L1 不同表达程度进行亚组分析，在延长OS方面，TPS<1%时，单药PD-1抑制剂二线治疗晚期ESCC无明显优势；而 TPS≥1%、TPS<5%、TPS≥5%、TPS<10%、TPS≥10%时，单药PD-1抑制剂二线治疗均可显著延长晚期ESCC患者的OS，且PD-L1表达程度越高，疗效获益更显著。然而，与化疗组比，单药PD-1抑制剂在延长晚期ESCC患者的无进展生存期（PFS） （HR＝0.93，95% CI：0.79~1.10，P=0.41）及提高客观有效率（ORR） （RR＝1.62，95% CI：0.95~2.74，P=0.07）等方面，差异均无统计学意义。但单药PD-1抑制剂组3~5级不良反应发生率低（RR＝0.37，95% CI：0.28~0.50，P<0.000 01）。 结论： 单药PD-1抑制剂二线治疗晚期 ESCC 患者可显著延长患者的OS；PD-L1高表达者PD-1抑制剂可作为二线治疗的优先选择，且具有良好的安全性。

Objective: To systematically review the effectiveness and safety of single-agent programmed cell death-1 (PD-1) inhibitors versus the second-line chemotherapy in advanced esophageal squamous cell carcinoma (ESCC) patients in order to provide optimal evidence-based medical proof for clinical decision-making. Methods: Relevant literatures about randomized controlled trails (RCTs) of single-agent PD-1 inhibitors versus traditional second-line chemotherapy in treating advanced ESCC patients were retrieved through The Cochrane Library, Web of science, PubMed, EMbase, CNKI and Wanfang data, J Clin Oncol, N England Oncol and Lancet Oncol, etc. as well as ASCO and ESMO meeting abstract. The data were extracted for Meta-analysis which was conducted using RevMan5.3 software. Results: Totally 5 RCT with 1732 patients were included in this study. The Meta-analysis showed that compared with chemotherapy, single-agent PD-1 inhibitors significantly prolonged the OS (overall survival) (HR＝0.75, 95% CI: 0.67-0.83, P<0.000 01) of advanced ESCC patients. In the sub-group analysis based on different PD-L1 expression, results showed that while the TPS<1%, second-line single-agent PD-1 inhibitors showed no obvious advantage in extending the OS of advanced ESCC patients; but when TPS≥1%, TPS<5%, TPS≥5%, TPS<10% or TPS≥10%, single- agent PD-1 inhibitors significantly prolonged the OS of advanced ESCC patients, with more significant effect in patients with higher PD-L1 level. However, there was no statistical significance in prolonging PFS (progression-free survival) (HR＝0.93, 95% CI: 0.79-1.10, P=0.41) or increasing ORR (objective response rate) (RR=1.62, 95% CI: 0.95-2.74, P=0.07) between single-agent PD-1 inhibitors and chemotherapy. Compared with chemotherapy group, the incidence of grade 3-5 treatment-related adverse effect was lower in the single drug PD-1 inhibitor group (RR=0.37, 95% CI: 0.28-0.50, P<0.000 01). Conclusion: Second-line single-agent PD-1 inhibitors can significantly prolong the OS of advanced ESCC patients with good safety. Single-agent PD-1 inhibitors should be used as the preferential second-line treatment in advanced ESCC patient with high PD-L1 expression.

R735.1; R730.2; R730.7

新疆维吾尔自治区自然科学基金资助项目（No. 2021D01C352）