阿美替尼二线治疗表皮生长因子受体突变的晚期非小细胞肺癌真实世界研究

Real-world study of second-line almonertinib for the treatment of advanced non-small cell lung cancer with epidermal growth factor receptor mutations

目的探讨真实世界中阿美替尼二线治疗表皮生长因子受体(EGFR)突变的晚期非小细胞肺癌(NSCLC)的预后、疗效以及影响患者生存的独立预后因素。方法回顾性分析2020-03-01-2023-07-31哈尔滨医科大学附属肿瘤医院在一线EGFR酪氨酸激酶抑制剂(EGFR-TKIs)治疗进展后接受阿美替尼序贯治疗的99例NSCLC患者临床资料。评估患者无进展生存期(PFS)、总生存期(OS)、疾病控制率(DCR)及颅内疾病控制率(IC-DCR),采用单因素及多因素Cox比例风险回归模型分析影响患者生存的独立预后因素。结果99例患者中,脑转移占52.53%(52/99),T790M^(+)占53.54%(53/99)。患者中位PFS为12.6个月(95%CI:10.7~17.4),中位OS为32.3个月(95%CI:23.8~NA),DCR为93.94%(93/99),IC-DCR为92.31%(48/52)。在单因素及多因素Cox回归分析中,功能状态(PS)评分≥2分(HR=2.181,P=0.007)、奥希替尼一线治疗(HR=10.033,P=0.041)、T790M突变未知(HR=3.086,P=0.004)和有脑转移(HR=1.910,P=0.040)是PFS的独立危险因素,而T790M^(+)(HR=0.393,P=0.034)、进展后未停用阿美替尼(HR=0.106,P<0.001)是影响PFS的保护性因素。男性患者(HR=2.550,P=0.010)、PS≥2分(HR=2.888,P=0.011)、21861Q/18 G719X突变(HR=12.623,P=0.004)、奥希替尼一线治疗(HR=70.605,P=0.001)、阿法替尼一线治疗(HR=56.203,P=0.001)、有脑转移(HR=4.585,P=0.001)是OS的独立危险因素,而感染新型冠状病毒(HR=0.125,P=0.001)是影响OS的保护性因素。在脑转移亚组中,基线有脑转移(HR=0.364,P=0.005)、脑转移病灶数≥3个(HR=2.570,P=0.005)是PFS的独立预后因素,脑转移病灶数≥3个(HR=2.560,P=0.029)是OS的独立预后因素。结论真实世界中,阿美替尼二线治疗EGFR突变的晚期NSCLC患者疗效良好,尤其对有脑转移患者疗效更为突出。

Objcctive To investigate the real-world prognosis,efficacy,and independent prognostic factors that influence the survival outcomes of patients with epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC)who received second-line treatment with almonertinib.Methods We retrospectively analyzed the clinical data of 99 patients with NSCLC,who underwent almonertinib sequential therapy after the progression of first-line EGFRtyrosine kinase inhibitors(EGFR-TKIs)in the Harbin Medical University Cancer Hospital from March 1,2020 to July31,2023.The primary objective was to evaluate the overall survival(OS),progression-free survival(PFS),disease control rate(DCR),and intracranial disease control rate(IC-DCR)of the patients.Additionally,univariate and multifactorial Cox regression analysis was carried out to identify the independent prognostic factors affecting survival.Results Among the 99 patients,52.53%(52/99)were diagnosed with brain metastasis,and 53.54%(53/99)were diagnosed with T790M^(+).The median PFS was 12.6 months(95%CI:10.7-17.4),and the median OS was 32.3 months(95%CI:23.8-NA).The DCR and IC-DCR were 93.94%(93/99)and 92.31%(48/52),respectively.In univariate and multivariate Cox regression analysis,performance status(PS)score≥2(HR=2.181,P=0.007),osimertinib first-line therapy(HR=10.033,P=0.041),T790M mutation unknown(HR=3.086,P=0.004)and brain metastasis(HR=1.910,P=0.040)were the independent risk factors for PFS,while the T790M^(+)(HR=0.393,P=0.034)and the continuation of almonertinib after progression(HR=0.106,P<0.001)were protective factors affecting PFS.On the other hand,male patients(HR=2.550,P=0.010),PS≥2(HR=2.888,P=0.011),21861Q/18 G719X mutation(HR=12.623,P=0.004),osimertinib first-line therapy(HR=70.605,P=0.001),first-line therapy with afatinib(HR=56.203,P=0.001)and presence of brain metastasis(HR=4.585,P=0.001)were the independent risk factors for OS,while infection with corona virus disease 2019(HR=0.125,P=0.001)was a protective factor affecting OS.Within the brain metastasis subgroup,baseline brain metastasis(HR=0.364,P=0.005)and the number of brain metastatic lesions≥3(HR=2.570,P=0.005)were independent prognostic factors for PFS,and the number of brain metastatic lesions≥3(HR=2.560,P=0.029)was an independent prognostic factor for OS.Conclusion The use of almonertinib as second-line therapy for advanced NSCLC patients with EGFR-mutation has shown promising efficacy in real-world settings,particularly in those with brain metastasis.