PD-L1高表达晚期非小细胞肺癌患者单纯免疫治疗与免疫联合化疗疗效比较

Evaluation of Response to Immune Checkpoint Inhibitor Monotherapy or Combination with Chemotherapy for Patients with Advanced Non-small Cell Lung Cancer and High PD-L1 Expression

背景与目的以免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)为代表的免疫治疗越来越广泛地应用于肺癌治疗。然而,对于程序性死亡受体配体1(programmed cell death-ligand 1,PD-L1)高表达,即肿瘤比例评分(tumor proportion score,TPS)≥50%的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者,采用单纯免疫治疗还是免疫联合化疗在临床上仍存争议。本研究旨在评估PD-L1高表达的晚期NSCLC患者接受单纯免疫治疗与免疫联合化疗的疗效。方法本研究回顾性分析了49例PD-L1高表达晚期NSCLC患者的临床资料。PD-LI表达采用22C3抗体行免疫组化染色,按TPS判读PD-L1表达水平。比较不同临床特征分组患者的客观缓解率(objective response rate,ORR)和无进展生存时间(progression free survival,PFS)。结果免疫单药与免疫联合化疗组的ORR分别为47.1%(8/17)和43.8%(14/32),差异无统计学意义(P=0.825)。免疫单药与免疫联合化疗组的中位PFS分别为8.0个月和6.8个月,差异无统计学意义(P=0.502)。并对本组PD-L1高表达患者免疫治疗的预测因素进行了分析,结果显示,一线免疫治疗0RR(12/19,63.2%)显著优于二线及以上免疫治疗(10/30,33.3%),差异有统计学意义(P=0.041),二者间PFS无差异。年龄、性别、吸烟史、功能状态评分(performance states,PS)、病理类型、肿瘤大小、肿瘤淋巴结转移(tumor node metastasis,TNM)分期与ORR和PFS不相关。结论PD-L1高表达的晚期NSCLC患者接受免疫单药和免疫联合化疗的疗效相近。PD-L1高表达患者一线免疫治疗的ORR更佳。对此类人群的最佳治疗方案有待于前瞻性临床研究进一步探索。

Background and objective Immunotherapy represented by immune checkpoint inhibitors(ICIs)has been widely used in the treatment of lung cancer.There are controversies in clinical practice for patients with advanced non-small cell lung cancer(NSCLC)and high programmed cell death-ligand 1(PD-L1)expression receiving ICIs monotherapy or combination chemotherapy.Methods This study retrospectively analyzed the clinical data of 49 patients with advanced NSCLC and high PD-L1 expression.Immunohistochemistry was performed with 22C3 antibody,and the expression level of PD-L1 was evaluated according to tumor proportion score(TPS).Objective response rate(ORR)and progression free survival(PFS)were compared by groups of different clinical characteristics.Results ORR of monotherapy and combination therapy group was 47.1%(8/17)and 43.8%(14/32),respectively,without statistical difference(P=0.825).The median PFS of monotherapy and combination therapy group was 8.0 months and 6.8 months,respectively,without statistical difference(P=0.502).Statistical analysis of predictors of immunotherapy for the patients showed first-line immunotherapy had better ORR than subsequent immunotherapy(12/19,63.2% vs 10/30,33.3%,P=0.041),however no difference in PFS.And there were no differences in ORR or PFS among groups of age,gender,smoking status,performance status(PS),pathological type,tumor size and tumornode-metastasis(TNM)stage.Conclusion The therapeutic effect is similar between ICIs monotherapy and combination chemotherapy for patients with advanced NSCLC and high PD-L1 expression.ORR of first-line immunotherapy was better in patients with advanced NSCLC and high PD-L1 expression.The optimal treatment for this population remains further prospective clinical studies.