免疫治疗后进展的晚期非小细胞肺癌二线继续免疫治疗联合化疗的回顾性分析

Retrospective Study on Immune Checkpoint Inhibitors as Cross-line Therapy Combined with Chemotherapy in Non-small Cell Lung Cancer

[目的]探讨一线程序性细胞死亡受体1(programmed cell death-1 receptor,PD-1)单抗进展后,二线继续PD-1单抗联合化疗治疗晚期非小细胞肺癌的临床疗效及预后。[方法]回顾性分析21例一线治疗采用PD-1单抗(帕博利珠单抗)联合或不联合含铂双联化疗治疗后进展,二线继续PD-1单抗(更换为信迪利单抗)联合化疗的晚期非小细胞肺癌。采用Kaplan-Meier生存曲线分析无进展生存期和总生存期,采用Cox回归模型进行多因素分析和评估预后因素。[结果]一线进展后更改为二线化疗方案并继续联合不同的PD-1单抗治疗,临床有效率为38.1%,疾病控制率为66.7%。程序性细胞死亡配体1(programmed cell death-1 ligand,PD-L1)表达阳性者和阴性者之间的疾病控制率并无统计学差异(P=0.217)。二线治疗的无进展生存时间(即二线治疗开始至疾病进展或死亡)为5.1个月。Cox多因素回归分析显示二线治疗的无进展生存时间与病理类型和PD-L1表达均无相关性。21例患者的中位总生存时间为17.6个月。Cox多因素回归分析显示,PD-L1表达是影响患者总生存的独立因素(HR=0.095,95%CI:0.018~0.494,P=0.005)。以PD-L1表达分层,亚组分析显示PDL1阳性患者的中位总生存期为21.0个月(95%CI:16.003~25.696);PD-L1阴性患者的中位总生存期为13.1个月(95%CI:10.708~15.492)(P=0.001)。[结论]一线进展后更换不同的PD-1单抗联合化疗有效,值得进一步研究。

[Objective]To explore the efficacy of immune checkpoint inhibitor(ICI)as second-line therapy combined with chemotherapy in non-small cell lung cancer(NSCLC)after the progress of first-line immunotherapy.[Methods]Clinical data of 21 patients with advanced NSCLC,who experienced the progress after first-line immunotherapy(pembrolizumab)combined with or without chemotherapy,and treated with second-line immunotherapy(sintilimab)combined with chemotherapy were analyzed.The Kaplan-Meier curve was used to analyse the progress-free survival(PFS)and overall survival(OS).The multivariate Cox regression model was used for analysis of factors related to survival of patients.[Results]Of 23 enrolled patients,the overall response rate(ORR)was 38.1%and disease control rate(DCR)was 66.7%.There was no significant differences in DCR between patients with positive and negative expression of PD-L1(P=0.217).PFS of second-line treatment was 5.1 months.Cox regression multivariate analysis showed pathological type and PD-L1 expression were not significantly correlated with PFS.The median OS of patients was 17.6 months.Cox regression multivariate analysis showed that PD-L1 expression was an independent protective factor for OS(HR=0.095,95%CI:0.018~0.494,P=0.005).Subgroup analysis showed that the median OS in PD-L1-positive and PD-L1-negative patients was 21.0 months(95%CI:16.003~25.696)and 13.1 months(95%CI:10.708~15.492),respectively(P=0.001).[Conclusion]Immune checkpoint inhibitors as second-line therapy combined with chemotherapy may achieve encouraging results both in efficacy and survival for patients with advanced NSCLC.