程序性死亡受体1抑制剂与安罗替尼联合治疗晚期非小细胞肺癌的临床效果

Clinical Efficacy of Programmed Death Receptor 1 Inhibitor Combined with Anlotinib against Advanced Non-small Cell Lung Cancer

目的基于倾向性评分匹配随机对照方法探讨晚期驱动基因阴性非小细胞肺癌患者接受程序性死亡受体1抑制剂与安罗替尼联合治疗的临床效果。方法选取某医院晚期驱动基因阴性非小细胞肺癌患者,按照随机数字表法分为两组,利用倾向性匹配法获取组间协变量均衡的样本。单药组给予安罗替尼,联合组在单药组基础上给予程序性死亡受体1抑制剂信迪利单抗。比较两组疗效、治疗前后肿瘤相关因子、T淋巴细胞亚群(CD3^(+)、CD4^(+)、CD8^(+))、NK细胞及不良反应,随访3年,采用Kaplan-Meier曲线统计比较两组3年生存率、无进展生存期、中位总生存期。结果联合组客观缓解率50.00%(15/30)、疾病控制率80.00%(24/30)高于单药组23.33%(7/30)、53.33%(16/30)(P<0.05);治疗6周后联合组血清癌胚抗原、糖类抗原125、细胞角蛋白19片段水平低于单药组(P<0.05);联合组治疗6周后外周血CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)、NK细胞水平高于单药组(P<0.05),CD8^(+)水平低于单药组(P<0.05);两组胃肠道反应、骨髓抑制、甲状腺功能减退、肝功能异常发生率无统计学差异(P>0.05);随访3年,联合组3年生存率为37.93%(11/29)高于单药组14.29%(4/28)(P<0.05),联合组无进展生存期为8.91个月,中位总生存期为13.57个月,单药组无进展生存期为6.13个月、中位总生存期为9.77个月。结论程序性死亡受体1抑制剂与安罗替尼联合治疗能显著提高晚期驱动基因阴性非小细胞肺癌的疗效,抑制肿瘤相关因子表达,减少肿瘤免疫逃逸,提高3年生存率,延长生存期。

Objective To explore the clinical effect of programmed death receptor 1 inhibitor com-bined with Anlotinib in patients with advanced driver gene negative non-small cell lung cancer based on the propensity score-matched randomized controlled method.Methods Patients with advanced driver gene-negative non small cell lung cancer treated in our hospital were selected and randomly divided into two groups using a random number table method before the propensity matching method was used to obtain samples with balanced covariates between the groups.The single-drug group was given Anlotinib while the combination group additionally received the programmed death receptor 1 inhibitor(sintilimab).The efficacy,tumor-related factors before and after treatment,T lymphocyte subsets(CD3^(+),CD4^(+),CD8^(+)),NK cells,and adverse reactions were compared between the two groups.After a follow-up of 3 years,Kap-lan-Meier curve statistics was used to compare the 3-year survival rate,progression-free survival,and me-dian overall survival between the two groups.Results The objective relief rate and disease control rate of the combination group were 50.00%(15/30)and 80.00%(24/30),respectively,which were higher than those of the single-drug group(23.33%and 53.33%,respectively)(P<0.05).After 6 weeks of treatment,the levels of serum carcinoembryonic antigen,carbohydrate antigen 125,and cytokeratin 19 frag-ment in the combination group were lower than those of the single-drug group(P<0.05).In addition,the levels of peripheral blood CD3^(+),CD4^(+),CD4^(+)/CD8^(+),and NK cells in the combination group were higher than those of the single-drug group(P<0.05),but the level of CD8^(+)was lower(P<0.05).There was no significant difference in the incidence of gastrointestinal reactions,bone marrow suppression,hypothy-roidism,and liver dysfunction between the two groups(P>0.05).After a follow-up of 3 years,the 3-year survival rate of the combination group was 37.93%(11/29),which was higher than that of the single-drug group(14.29%and 4/28,respectively)(P<0.05).The progression-free survival of the combination group was 8.91 months,and the median overall survival was 13.57 months,compared with 6.13 months and 9.77 months respectively in the single-drug group.Conclusion The combination of programmed death receptor 1 inhibitor and Anlotinib in the treatment of patients with advanced driver gene-negative non-small cell lung cancer can significantly improve the efficacy,inhibit the expressions of tumor-related factors,reduce tumor immune escape,increase 3-year survival rate,and prolong survival.