免疫化疗的给药顺序对非小细胞肺癌患者疗效及不良反应的影响

Effect of immunochemotherapy administration sequence on efficacy and adverse reactions in patients with non-small cell lung cancer

目的:探讨化疗联合程序性死亡蛋白-1(programmed cell death protein-1,PD-1)单抗治疗的给药顺序对晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者疗效及免疫相关不良事件(immune-related adverse events,irAEs)的影响。方法:回顾性分析2019年11月至2022年1月于郑州大学第一附属医院收治的110例晚期NSCLC患者的临床资料。通过单因素及多因素Logistic回归分析irAEs发生的影响因素,并通过Kaplan-Meier曲线、Log-rank检验、单因素及多因素Cox回归分析疗效的影响因素。结果:110例晚期NSCLC患者中36例采用化疗2天后行PD-1单抗治疗(序贯治疗组),相比74例采用化疗当天行PD-1单抗治疗(同时治疗组)的无进展生存期(progression-free survival,PFS)显著延长(17.2个月vs.11.3个月,P<0.05)。序贯治疗组的疾病控制率(disease control rate,DCR)为94.4%优于同时治疗组的79.7%(P=0.045),客观缓解率(objective response rate,ORR)为69.4%和51.4%,两组比较无显著性差异(P=0.072)。Cox回归分析显示细胞角蛋白19片段(cytokeratin19 fragment,Cyfra21-1)及D-二聚体是联合治疗疗效的影响因素(P<0.05)。Logistic回归分析显示年龄及乳酸脱氢酶(lactic dehydrogenase,LDH)是irAEs发生的影响因素(P<0.05),而给药顺序对irAEs的发生无显著影响(P=0.130)。结论:给药顺序是联合治疗疗效的影响因素之一,接受序贯治疗的晚期NSCLC患者可能会得到更好的治疗效果。年龄及LDH与irAEs的发生呈负相关。

Objective:To explore the effect of chemotherapy administration sequence combined with programmed cell death protein-1(PD-1)monoclonal antibody on the efficacy and immune-related adverse events(irAEs)in patients with advanced non-small cell lung cancer(NSCLC).Methods:The clinical data of 110 patients with advanced NSCLC treated at The First Affiliated Hospital of Zhengzhou University between November 2019 and January 2022 were retrospectively collected.The factors influencing irAEs were analyzed by univariate and multivariate Logistic regression analyses,while those influencing curative effect were analyzed by Kaplan-Meier curve analysis,Log-rank test,and univariate and multivariate Cox regression analyses.Results:Treatment with PD-1 monoclonal antibody after 2 days of chemotherapy(sequential treatment group,n=36)significantly prolonged progression-free survival(PFS)compared with PD-1 monoclonal antibody administration on the same day of chemotherapy(simultaneous treatment group,n=74)(17.2 months vs.11.3 months,respectively;P<0.05).The disease control rate(DCR)was better in the sequential treatment group than in the simultaneous treatment group(94.4%vs.79.7%,respectively;P=0.045),while the objective response rate(ORR)did not differ significantly(69.4%vs.51.4%,respectively;P=0.072).The Cox regression analysis showed that cytokerat in 19 fragment(Cyfra21-1)and d-dimer(D-dimer)affected the efficacy of combination therapy(P<0.05).The Logistic regression analysis showed that age and lactic dehydrogenase(LDH)influenced the occurrence of irAEs(P<0.05),while the administration sequence did not significantly affect the occurrence of irAEs(P=0.130).Conclusions:Administration sequence influences the efficacy of combination therapy,and patients with advanced NSCLC who receive sequential therapy may experience better efficacy.Age and LDH are negatively correlated with the occurrence of irAEs.