联合PD-1/L1免疫检查点抑制剂方案用于EGFR-TKIs耐药后晚期非小细胞肺癌的疗效分析

doi:10.20223/j.cnki.1000-8535.2024.12.008

摘要/Abstract

摘要： 目的探讨表皮生长因子受体酪氨酸酶抑制剂（EGFR-TKIs）一线治疗耐药后,二线化学治疗（化疗）联合程序性死亡蛋白1及其配体（PD-1/L1）免疫检查点抑制剂方案对晚期非小细胞肺癌（NSCLC）的疗效。方法选取2018年 6月—2022年10月期间就诊于南通大学附属肿瘤医院院的80例有完整临床资料、应用EGFR-TKIs耐药后晚期NSCLC患者进行回顾性分析,依照不同治疗方式将患者分为观察组与对照组,均为40例。对照组一线EGFR-TKIs治疗耐药后进行二线化疗,观察组一线EGFR-TKIs治疗耐药后进行二线化疗联合PD-1/L1免疫检查点抑制剂治疗。对比两组临床疗效及无进展生存期（PFS）,化疗前后血清中人细胞角蛋白21-1片段（Cyfra21-1）、糖类抗原125（CA125）、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）水平变化,不良反应发生率及生存质量。结果观察组客观缓解率与疾病控制率高于对照组（P<0.05）,对照组PFS为10（2.38,24.13）个月,观察组PFS为14（5.27~,5.27）个月,观察组高于对照组（χ²=4.536,P=0.041）;化疗后两组bFGF、VEGF,CA125、Cyfra21-1肿瘤标志物水平均比化疗前降低,且观察组[（17.85±3.32）ng/L、（310.51±88.37）ng/L、（51.62±13.66）U/mL、（10.26±3.37）ng/mL]低于对照组[（19.62±3.24）ng/L、（366.26±49.42）ng/L、（59.26±9.35）U/mL、（12.62±2.73）ng/mL],对比差异有统计学意义（t₁=2.413,P₁=0.018;t₂=3.482,P₂<0.001;t₃=2.919,P₃=0.005;t₄=3.442,P₄<0.001）;两组不良反应发生率对比差异无统计学意义（P>0.05）;化疗后两组世界卫生组织生存质量量表简表评分均升高,观察组[（98.62±8.24）、（101.53±12.62）、（95.28±11.15）、（97.79±10.47）分]高于对照组[（84.25±7.32）、（93.58±15.75）、（82.24±9.34）、（83.47±8.38）]分,对比差异有统计学意义（t₁=8.246,P₁<0.001;t₂=2.491,P₂=0.015;t₃=5.670,P₃<0.001;t₄=6.753,P₄<0.001）。结论对EGFR-TKIs耐药后晚期非小细胞肺癌患者采取二线化疗联合PD-1/L1免疫检查点抑制剂可提升其临床疗效及生存期,改善血清相关肿瘤标志物表达水平,提升患者生存质量。

关键词: PD-1/L1免疫检查点抑制剂, EGFR-TKIs耐药, 非小细胞肺癌, 晚期, 安全性, 生存质量

Abstract: Objective To explore the therapeutic effect of second-line chemotherapy combined with PD-1/L1 immune checkpoint inhibitor regimen on advanced non-small cell lung cancer（NSCLC） after epidermal growth factor receptor-tyrosine kinase inhibitors（EGFR-TKIs）resistance in first-line chemotherapy．Methods Retrospectively selected 80 patients with advanced NSCLC EGFR TKIs resistance,who were admitted to the Affiliated Cancer Hospital of Nantong University from June 2018 to October 2022．Patients were divided into an observation group and a control group according to different treatment methods,with 40 cases in each group．The control group received second-line chemotherapy after first-line EGFR-TKIs therapy resistance,while the observation group received second-line chemotherapy and PD-1/L1 inhibitor after first-line EGFR-TKIs therapy reactions and quality of live．Clinical efficacy and PFS,changes in serum levels of human Cyfra21-1,CA125,bFGF,VEGF,incidence of adverse chemotherapy of two groups were compared．Results The ORR and DCR of the observation group were significantly higher than those of the control group（P<0.05）．The mean PFS of the control group was 10（2.38-24.13）months,while the mean PFS of the observation group was 14（5.27-35.27）months．The observation group was higher than the control group（χ²=4.536,P=0.041）．After chemotherapy,levels of bFGF,VEGF,CA125 and Cyfra21-1 tumor markers decreased in both groups,and the observation group [（17.85±3.32）ng/L,（310.51±88.37）ng/L,（51.62±13.66）U/mL,（10.26±3.37）ng/mL] was lower than the control group [（19.62±3.24）ng/L,（366.26±49.42）ng/L,（59.26±9.35）U/mL,（12.62±2.73）ng/mL],which showed statistically significant difference in the comparison（t₁=2.413,P₁=0.018;t₂=3.482,P₂<0.001;t₃=2.919,P₃=0.005;t₄=3.442,P₄<0.001）．There was no significant difference in the incidence of adverse reactions between the two groups（P>0.05）．After treatment,the WHO QOL-BREF scores increased in both patient groups and the observation group scores[（98.62±8.24）,（101.53±12.62）,（95.28±11.15）,（97.79±10.47）] were higher than the control group scores[（84.25±7.32）,（93.58±15.75）,（82.24±9.34）,（83.47±8.38）],which showed statistically significant difference．（t₁=8.246,P₁<0.001;t₂=2.491,P₂=0.015;t₃=5.670,P₃<0.001;t₄=6.753,P₄<0.001）．Conclusions The combination of second-line chemotherapy with PD-1/L1 immune checkpoint inhibitors can improve the clinical efficacy and survival of advanced NSCLC patients who are resistant to EGFR-TKIs,improve the expression levels of serum related tumor markers,and enhance the quality of life of patients．

Key words: PD-1/L1 immune checkpoint inhibitor, EGFR-TKIs resistance, late stage, non small cell lung cancer, security, quality of life

葛建娟, 施向荣, 周艳, 谭清和, 李剑英. 联合PD-1/L1免疫检查点抑制剂方案用于EGFR-TKIs耐药后晚期非小细胞肺癌的疗效分析[J]. 广州医药, 2024, 55(12): 1437-1443.

GE Jianjuan, SHI Xiangrong, ZHOU Yan, TAN Qinghe, LI Jianying. Efficacy analysis of the combined PD-1/L1 immune checkpoint inhibitor regimen for advanced non-small cell lung cancer after EGFR TKIs resistance[J]. Guangzhou Medical Journal, 2024, 55(12): 1437-1443.

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