免疫检查点抑制剂治疗EGFR-TKI耐药晚期非小细胞肺癌的疗效及不良反应

目的:探讨免疫检查点抑制剂(immune checkpoint inhibitor,ICI)治疗表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)耐药晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及不良反应。方法:收集2015年1月至2019年3月在解放军总医院接受ICI治疗的EGFR-TKI耐药晚期NSCLC患者临床资料,采用统计学方法分析EGFR-TKI耐药晚期NSCLC患者免疫治疗疗效及不良反应,阐明临床特征与免疫治疗疗效和患者预后的关系。结果:联合治疗较单药治疗者肿瘤客观缓解率(objective response rate,ORR)显著提高(28.6%vs.7.1%,P<0.01)。肿瘤分化差、联合治疗及年龄>60岁者分别较肿瘤分化好(5.1个月vs.2.8个月,P=0.030)、单药治疗(6.8个月vs.2.3个月,P<0.001)及年龄≤60岁者(7.1个月vs.4.7个月,P=0.020)无进展生存期(progression free survival,PFS)延长。联合治疗、肿瘤治疗缓解者分别较单药治疗(26.9个月vs.7.1个月)、肿瘤稳定者和进展者(30.8个月vs.18.7个月vs.12.8个月)总生存期(overall survival,OS)延长(P<0.001)。多因素分析显示年龄>60岁和联合治疗是PFS独立保护性因素(P<0.001)。联合治疗组的总体不良反应发生率较单药治疗组升高,但≥3级不良反应发生率两组间无显著性差异(P=0.28)。结论:ICI单药治疗EGFR-TKI耐药晚期NSCLC患者的疗效较差,而联合治疗能显著提高疗效,改善患者的预后。尽管联合治疗的总体不良反应发生率较高,但大体上不良反应可控。

Efficacy and adverse effects of immune checkpoint inhibitor for advanced epidermal growth factor receptor tyrosine kinase-resistant non-small cell lung cancer

  Objective  To investigate the efficacy and adverse effects of immune checkpoint inhibitor (ICI) for advanced non-small cell lung cancer (NSCLC) resistant to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).  Methods  The clinical data of 49 patients with advanced NSCLC who received ICI treatment after EGFR-TKI resistance in the Chinese People's Liberation Army General Hospital from January 2015 to March 2019 were collected. Statistical methods were used to analyze the efficacy and adverse effects of immunotherapy in patients with EGFR TKI-resistant NSCLC, and to clarify the relationship between clinical characteristics and the curative efficacy and prognosis of patients.  Results  The objective response rate was significantly higher in patients with combination therapy than those with monotherapy (28.6% vs. 7.1%, P < 0.01). Patients with poor differentiation, combination therapy, and age >60 years had longer progression free survival than those with moderate differentiation (5.1 vs. 2.8 months, P=0.03), monotherapy (6.8 vs. 2.3 months, P < 0.001), and age ≤ 60 years (7.1 vs. 4.7 months, P=0.02), respectively. The overall survival of patients with combination therapy and tumor response was longer than those with monotherapy (26.9 vs. 7.1 months, P < 0.001), stable disease and progression (30.8 vs. 18.7 vs. 12.8 months, P < 0.001), respectively. Multivariate analysis showed that age >60 years and combination therapy were independent protective factors for PFS (P < 0.001). Although combination therapy group had higher overall adverse event rate than monotherapy group, there was no significant difference in the adverse reaction rate of grade 3 and above between both groups (P=0.28).  Conclusions  The efficacy of monotherapy with ICI was poor in EGFR TKI-resistant patients with late-stage NSCLC, while combination therapy could significantly improve the curative efficacy and prognosis of patients. Although the overall rate of adverse events was higher in patients with combination therapy, adverse events were controllable.