基于真实世界的晚期食管鳞癌一线标准化疗联合免疫检查点抑制剂对比标准化疗的回顾性对照研究

Real-world retrospective controlled study of first-line standard chemotherapy combined with immune checkpoint inhibitor versus standard chemotherapy for advanced esophageal squamous cell carcinoma

目的 在真实世界中探索晚期食管鳞癌(Esophageal squamous cell carcinoma, ESCC)患者一线应用免疫检查点抑制剂联合标准化疗对比单纯标准化疗之间的疗效和安全性差异以及预后相关因素。方法 回顾性分析2018年1月—2020年12月在哈尔滨医科大学附属肿瘤医院就诊的未经过系统治疗的107例局部晚期或转移性ESCC患者的临床资料。根据其一线治疗方案分为应用程序性细胞死亡蛋白-1(Programmed cell death-1,PD-1)抑制剂联合化疗组(联合化疗组)和单纯标准化疗组(单纯化疗组),比较两组的无进展生存期(Progression-free survival, PFS)、客观缓解率(Objective response rate, ORR)、疾病控制率(Disease control rate, DCR)以及治疗相关不良反应(Treatment-related adverse events, TRAEs)发生情况,并且寻找与晚期ESCC患者PFS相关的影响因素。结果 共收集107例(联合化疗组56例,单纯化疗组51例)患者资料,经倾向评分匹配(Propensity score matching, PSM)后获得联合化疗组和单纯化疗组各31例。联合化疗组对比单纯化疗组的ORR差异无统计学意义(38.7%vs. 19.4%,P>0.05);DCR差异无统计学意义(96.8%vs. 90.3%,P>0.05);两组PFS差异具有统计学意义(中位PFS:11.87个月vs. 7.7个月,P=0.001)。Cox回归分析显示是否使用PD-1抑制剂以及病灶位置是PFS的独立影响因素。联合化疗组和单纯化疗组TRAEs发生率分别为80.6%和67.7%,联合化疗组中有5例(16.1%)发生免疫相关不良事件(immune-related adverse events, irAEs),以上不良反应可耐受或经药物治疗后缓解,未影响化疗药物的使用。结论 在真实世界临床中,晚期ESCC患者一线应用免疫检查点抑制剂联合标准化疗的疗效优于单纯标准化疗。未观察到免疫治疗相关不良反应导致的停药。ESCC病灶位置位于上中段的患者预后优于病灶位于下段的患者。

Objective The aim of this study was to explore the efficacy, safety difference and prognostic factors between first-line immune checkpoint inhibitor combined with standard chemotherapy and standard chemotherapy alone in patients with advanced esophageal squamous cell carcinoma(ESCC)in the real world.Methods The clinical data of 107 patients with locally advanced or metastatic ESCC who were treated in our hospital from January 2018 to December 2020 were retrospectively analyzed.According to their first-line treatment schemes, they were divided into the application of programmed cell death protein-1(PD-1)inhibitors combined standard chemotherapy group and the standard chemotherapy group alone.The progression free survival(PFS),objective response rate(ORR),disease control rate(DCR)and the occurrence of treatment-related adverse events(TRAEs)were compared between of the two groups and influencing factors related to PFS in patients with advanced ESCC were analyzed.Results A total of 107 patients(56 in the combined treatment group and 51 in the chemotherapy group)were collected.After propensity score matching(PSM),31 patients in the combined treatment group and 31 patients in the chemotherapy group were obtained.There was no significant difference in ORR between the combined chemotherapy group and the chemotherapy alone group(38.7% vs. 19.4%,P>0.05);the difference in DCR was not statistically significant(96.8% vs. 90.3%,P> 0.05);the difference in PFS was statistically significant(median PFS:11.87 months vs. 7.7 months, P=0.001).Cox regression analysis showed that use of PD-1 inhibitors and the location of lesions were independent influencing factors of PFS.The incidence of TRAEs in the combined chemotherapy group and chemotherapy alone group were 80.6% and 67.7%,respectively, and 5 cases(16.1%)in the combined chemotherapy group had immune-related adverse events(irAEs),and the above adverse reactions were tolerable or relieved after drug treatment, without affecting the use of chemotherapy drugs.Conclusion In the real world clinical practice, the efficacy of first-line immune checkpoint inhibitor combined with standard chemotherapy in patients with advanced ESCC is better than that of standard chemotherapy alone.No discontinuation due to immunotherapy-related adverse reactions was observed.The prognosis of patients with ESCC lesions located in the upper and middle segments is better than that of patients with ESCC lesions located in the lower segment.