卡铂、多西他赛联合信迪利单抗对驱动基因阴性晚期肺腺癌的疗效及安全性分析

Efficacy and safety analysis of carboplatin,docetaxel combined with sintilimab in the treatment of advanced lung adenocarcinoma with negative driver genes

目的探讨卡铂、多西他赛联合信迪利单抗对驱动基因阴性晚期肺腺癌的疗效及安全性。方法回顾性分析2019—2021年首都医科大学附属北京友谊医院收治的76例驱动基因阴性的晚期肺腺癌患者的临床资料,根据治疗方案分为对照组(卡铂+多西他赛治疗,n=40)与研究组(卡铂+多西他赛+信迪利单抗治疗,n=36)。比较两组患者的临床疗效、治疗前后血肿瘤标志物和免疫细胞变化及不良反应。结果研究组的客观缓解率、疾病控制率、中位无进展生存时间和总生存时间明显优于对照组(均P<0.05)。两组治疗后血癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原125(carbohydrate antigen,CA125)、细胞角质蛋白19片段抗原21-1(cytokeratin-19 fragment antigen 21-1,CYFRA 21-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平及CD8^(+)T淋巴细胞、Treg细胞比例均明显低于治疗前(均P<0.05),血CD4^(+)T淋巴细胞比例、CD4^(+)/CD8^(+)T淋巴细胞比值均高于治疗前(均P<0.05)。研究组治疗后的血CEA、CA125、CYFRA 21-1、VEGF水平和CD8^(+)T淋巴细胞、Treg细胞比例、血CD4^(+)T淋巴细胞比例、CD4^(+)/CD8^(+)T淋巴细胞比值均低于对照组(均P<0.05)。两组患者的不良反应以骨髓抑制多见,程度多较轻(1~2级),且均相近(P>0.05)。结论在卡铂与多西他赛的化疗基础上,加用信迪利单抗能明显提高驱动基因阴性的晚期肺腺癌患者的肿瘤控制效果,降低血肿瘤标志物水平,改善免疫功能和预后。

Objective To investigate the efficacy and safety of carboplatin,docetaxel combined with sintilimab in the treatment of advanced lung adenocarcinoma with negative driver genes.Method This study retrospectively analyzed the clinical data of 76 advanced lung adenocarcinoma patients with negative driver genes admitted to Beijing Friendship Hospital,Capital Medical University from June 2019 to April 2021.They were divided into a control group(carboplatin+docetaxel treatment,n=40)and study group(carboplatin+docetaxel+sintilimab treatment,n=36)according to the treatment.The clinical efficacy,tumor markers or immune cell changes and toxicity before and after treatment were compared between the two groups.Result The objective remission rate,disease control rate,median progress free survival and overall survival of the research group were significantly higher than those of the control group(all P<0.05).Compared with the pre-treatment levels within the group,blood levels of carcinoembryonic antigen(CEA),carbohydrate antigen 125(CA125),cytokeratin-19 fragment antigen 21-1(CYFRA 21-1),vascular endothelial growth factor(VEGF),CD8^(+)T lymphocytes and Treg cells after treatment in the study group and control group were significantly decreased(all P<0.05),while the blood proportion of CD4^(+)T lymphocytes and CD4^(+)/CD8^(+)T lymphocytes ratio were significantly increased(all P<0.05).Compared with the levels of control group at the same period,the blood levels of CEA,CA125,CYFRA 21-1,VEGF,CD8^(+)T lymphocytes and Treg cells after treatment in study group were significantly decreased,while the blood proportion of CD4^(+)T lymphocytes and CD4^(+)/CD8^(+)T lymphocytes ratio were significantly increased(all P<0.05).The toxic side effects of the study group and the control group were more common in bone marrow suppression,and the degree was mostly mild(grade 1-2).There were no significant differences in the incidences of all toxic effects between the two groups(all P>0.05).Conclusion On the basis of the chemotherapy of carboplatin and docetaxel,the combination of sintilimab could significantly improve the tumor control effect of advanced lung adenocarcinoma patients with negative driving genes,reduce their blood level of tumor markers,and improve the immune function and prognosis.