老年EGFR突变非小细胞肺癌耐药后PD-1抑制剂免疫治疗37例临床分析  

Clinical Analysis of immunotherapy with PD-1 inhibitor in elderly EGFR mutated non-small cell lung cancer after acquired drug resistance

作　　者：鲁葆华[1] 李琨 张婵 张佩华 朱思宇 刘赞[1] 张红梅[1] 李雪冰[3] LU Baohua;LI Kun;ZHANG Chan;ZHANG Peihua;ZHU Siyu;LIU Zan;ZHANG Hongmei;LI Xuebing(General Department,Beijing Chest Hospital,Capital Medical University,Beijing 101149,China;Pathology Department,Beijing Chest Hospital,Capital Medical University,Beijing 101149,China;Oncology Department,Beijing Luhe Hospital,Capital Medical University,Beijing 101100,China)

机构地区：[1]首都医科大学附属北京胸科医院综合科,北京101149 [2]首都医科大学附属北京胸科医院病理科,北京101149 [3]首都医科大学附属北京潞河医院肿瘤科,北京101100

出　　处：《临床肺科杂志》2023年第11期1716-1722,共7页Journal of Clinical Pulmonary Medicine

基　　金：北京海凌公益基金会BJ-HL-20230101。

摘　　要：目的 分析老年晚期表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变非小细胞肺癌(non small cell lung cancer,NSCLC)患者应用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)继发耐药后应用程序性死亡受体1(programmed death 1,PD-1)抑制剂免疫治疗的疗效和耐受性。方法 回顾性收集65岁及以上晚期EGFR敏感突变的非小细胞肺癌患者在EGFR-TKI继发耐药后应用PD-1抑制剂免疫治疗患者37例,记录患者的临床、病理特征、治疗等情况。按照年龄是否小于或大于等于70岁,将患者分为两组。分析治疗效果以及耐受性,并评价其与患者年龄分组以及各临床病理特征的关系。结果 37例老年患者中疗效评价显示客观缓解率为27.0%,疾病控制率达到86.5%。患者接受免疫治疗1~30个周期,免疫治疗的无疾病进展生存期(progression free survival,PFS)波动于0.9~25.7个月,中位PFS为5.3个月。免疫治疗的PFS与患者的性别、年龄分组、EGFR突变类型、免疫治疗药物、免疫治疗前程序性死亡配体1(programmed death ligand1,PD-L1)表达状态无关。EGFR-TKI耐药后一线免疫治疗组PFS中位数为7.70(95%CI:4.97~10.43)个月较后线免疫治疗组的PFS 1.60(95%CI:0.00~6.35)个月延长,差异具有统计学意义(P=0.035)。共7例发生3级及以上的不良反应。其中3级肺炎2例(5.4%)。3级及以上的不良反应发生率在两个年龄组无差异。结论 晚期老年EGFR敏感突变非小细胞肺癌患者在EGFR-TKI继发耐药后早期应用PD-1抑制剂免疫联合治疗有较好临床疗效而且耐受性较好。Objective To analyze the efficacy and tolerability of Programmed Death receptor 1(PD-1)immunotherapy in elderly patients with advanced Epidermal Growth Factor Receptor(EGFR)sensitive mutated non-small cell lung cancer(NSCLC)after acquired drug resistance with the use of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor(EGFR-TKI).Methods 37 elderly patients with advanced NSCLC with EGFR sensitive mutations who were treated with PD-1 inhibitor immunotherapy after acquired resistance to EGFR-TKI were collected retrospectively.The clinical and pathological characteristics and treatment of the patients were recorded.Patients were divided into two groups according to their age of 70 years.The treatment effect and tolerance were analyzed,and the relationships between the Progression Free Survival(PFS)with the clinicopathological characteristics and age group of these patients were evaluated.Results Among the 37 patients,the objective response rate was 27.0%,and the disease control rate reached 86.5%.After 1 to 30 cycles of immunotherapy,the PFS of immunotherapy fluctuated from 0.9 months to 25.7 months.PFS of immunotherapy was not related to gender,age group,EGFR mutation type,immunotherapy drugs,and PD-L1 expression.After EGFR-TKI resistance,the median PFS of the first-line immunotherapy group was 7.70 months(95%CI:4.97~10.43 months)longer than that of the non-first-line immunotherapy group for 1.60 months (95% CI : 0.00~6.35 months), and the difference was statistically significant ( P =0.035). A total of 7 cases had grade 3 and above adverse events. There were 2 cases of grade 3 pneumonia (5.4%). There was no difference in grade 3 and above adverse reactions between the two age groups. Conclusion Early application of PD-1 inhibitor immunotherapy in elderly patients with advanced EGFR-sensitive NSCLC after acquired resistance to EGFR-TKI has good clinical efficacy and tolerance.

关 键 词：晚期 EGFR突变 非小细胞肺癌 PD-1免疫治疗 

分 类 号：R734.2[医药卫生—肿瘤]