【摘要】 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)、21 861Q/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。更多还原

【Abstract】 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),21 861Q/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.更多还原