关于PD-1/PD-L1免疫抑制剂治疗晚期食管癌疗效和安全性的Meta分析

The Efficacy and Safety of PD-1/PD-L1 Immunosuppressive Agents in Advanced Esophageal Cancer: A Meta-Analysis

摘要: 目的：系统评价PD-1/PD-L1免疫抑制剂应用于晚期食管癌的疗效和安全性。方法：检索PubMed、EMbase、Web of Science、The Cochrane Library、Clinical Trials等数据库搜寻关于PD-1/PD-L1免疫抑制剂治疗晚期食管癌的随机对照研究，并由两名独立人员筛选文献和提取相关数据。检索时限为2016年1月~2021年12月，并对纳入的研究文献进行评价，应用RevMan 5.3软件进行分析OR及其对应的95%置信区间。结果：按照纳入和排除标准，保留5项随机对照研究，包括1685例患者。Meta分析结果显示，免疫治疗组12个月总生存期(OS)发生率(OR = 1.95, 95% CI: 1.51~2.51, P < 0.00001)、18个月OS发生率(OR = 1.80, 95% CI: 1.28~2.52, P = 0.0007)和12个月无进展生存期(PFS)发生率(OR = 1.77, 95% CI: 1.15~2.72, P = 0.009)、18个月PFS发生率(OR = 2.10, 95% CI: 1.09~4.04, P = 0.03)均高于对照组，差异有统计学意义。针对PD-L1表达阳性(联合阳性评分CPS > 10)的亚组人群中，免疫治疗可明显提高12个月OS发生率(OR = 2.91, 95% CI: 1.56~5.41, P = 0.0008)。对于安全性方面，免疫治疗组总体不良发生率(OR = 0.26, 95% CI: 0.08~0.85, P = 0.03)，3~5级不良反应发生率(OR = 0.29, 95% CI: 0.12~0.75, P = 0.01)均小于对照组，且差异有统计学意义。结论：对于晚期食管癌患者，抗PD-1/PD-L1免疫治疗的疗效优于化疗或姑息治疗，且安全性高。

Abstract: Objective: To systematically evaluate the efficacy and safety of PD-1/PD-L1 immunosuppressive agents in advanced esophageal cancer. Method: The databases PubMed, EMBASE, web of science, the Cochrane Library, clinical trials were searched for randomized controlled studies on PD-1/ PD-L1 immunosuppressive therapy for advanced esophageal cancer, and two independent personnel screened the literature and extracted relevant data. The search time frame was from January 2016 to December 2021, and the literature of included studies was evaluated and RevMan 5.3 software was used to analyze OR and their corresponding 95% confidence intervals. Result: Following the inclusion and exclusion criteria, 5 RCTs including 1685 patients were retained. Meta analysis showed that the incidence of 12-month overall survival (OS) (OR = 1.95, 95% CI: 1.51~2.51, P < 0.00001), 18-month OS (OR = 1.80, 95% CI: 1.28~2.52, P = 0.0007) and 12-month progression free survival (PFS) (OR = 1.77, 95% CI: 1.15~2.72, P = 0.009) were higher in the immunotherapy group than in the control group, with significant differences. In the subgroup of patients with positive PD-L1 expression (combined positive score CPS > 10), immunotherapy significantly improved the 12-month OS rate (OR = 2.91, 95% CI: 1.56~5.41, P = 0.0008). In terms of safety, the overall incidence of adverse reactions (OR = 0.26, 95% CI: 0.08~0.85, P = 0.03) and the incidence of grade 3~5 adverse reactions (OR = 0.29, 95% CI: 0.12~0.75, P = 0.01) in the immunotherapy group were lower than those in the control group, and the difference was statistically significant. Conclusion: For patients with advanced esophageal cancer, the efficacy of anti-PD-1/PD-L1 immunotherapy is superior to that of chemotherapy or palliative therapy, and the safety profile is high.