目的：研究免疫治疗联合化疗和贝伐单抗在表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗失败的非小细胞肺癌（NSCLC）患者中的疗效和影响因素。方法：回顾性分析山东第一医科大学附属肿瘤医院2019年1月至2022年3月治疗失败的EGFR-TKIs的60例NSCLC患者的临床资料，这些患者接受了免疫治疗联合化疗和贝伐单抗。患者进行电话或门诊随访，截至2022年10月1日，中位随访时间为8.2个月（95％CI：7.1-9.3）。所有60名患者均进行了随访。使用固体肿瘤的响应评价标准评估短期疗效。根据不良事件的通用术语标准评估患者的不良反应。用Kaplan-Meier方法绘制生存曲线。利用Cox比例风险回归模型分析进展无瘤生存期（PFS）的影响因素。结果：在60例NSCLC患者中，22例为男性。年龄在41岁至75岁之间，中位年龄为61岁。11例患者部分缓解，19例患者稳定病情，30例患者病情进展。中位PFS为8.2个月（95％CI：7.2-9.2）。PD-L1低表达（肿瘤细胞比例分数[TPS]＜1％），PD-L1中度表达（1％≤TPS≤49％）和PD-L1高表达（TPS≥50％）的患者的中位PFS分别为6.4（95％CI：4.8-8.0）、8.3（95％CI：7.3-9.3）和10.6个月（95％CI：7.2-14.1），差异具有统计学意义（χ2=13.58，P<0.001）。多元Cox比例风险回归模型分析显示，年龄>65岁（HR=4.017，95％CI：1.468-10.992，P=0.007）是接受EGFR-TKIs治疗失败后接受免疫治疗联合化疗和贝伐单抗的NSCLC患者PFS的危险因素。PD-L1中度表达（HR=0.360，95％CI：0.139-0.930，P=0.035）和PD-L1高表达（HR=0.155，95％CI：0.039-0.625，P=0.009）是PFS的保护因素。整个组中大部分与治疗相关的不良反应均为1-2级，包括骨髓抑制（n=24）、恶心（n=25）、食欲减退（n=24）、疲劳（n=22）、呕吐（n=18）、肝功能异常（n=17）、血肌酐升高（n=10）等，患者能够耐受。结论：接受EGFR-TKIs治疗失败的NSCLC患者可以耐受与免疫治疗联合化疗和贝伐单抗治疗相关的不良反应。年龄≤65岁和PD-L1中度和高表达的患者的PFS显着延长。

Objective: To investigate the efficacy and influencing factors of immunotherapy combined with chemotherapy and bevacizumab in patients with non-small cell lung cancer (NSCLC) who failed epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. Methods: A retrospective analysis was made on the clinical data of 60 NSCLC patients who were treated with immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure in the Affiliated Cancer Hospital of Shandong First Medical University from January 2019 to March 2022. Patients were followed up by telephone or outpatient review up to October 1, 2022, with a median follow-up of 8.2 months (95%CI: 7.1-9.3). All 60 patients were followed up. The response evaluation criteria in solid tumors were used to evaluate the short-term efficacy. The adverse reactions of patients were evaluated according to the common terminology criteria for adverse events. The survival curve was drawn by Kaplan-Meier method. Cox proportional hazard regression models were utilized to analyze the influencing factors of progression-free survival (PFS). Results: Among the 60 NSCLC patients, 22 were males. The age ranged from 41 to 75 years, with a median age of 61 years. Eleven patients had partial response, 19 patients had stable disease and 30 patients had progressive disease. The median PFS was 8.2 months (95%CI: 7.2-9.2). The median PFS of patients with low expression of programmed death receptor-ligand 1 (PD-L1) [Tumor cell Proportion Score (TPS)<1%], moderate expression of PD-L1 (1%≤TPS≤49%), and high expression of PD-L1 (TPS≥50%) were 6.4 (95%CI: 4.8-8.0), 8.3 (95%CI: 7.3-9.3) and 10.6 months (95%CI: 7.2-14.1), respectively, and there were statistically significant differences (χ2=13.58, P<0.001). Multivariate Cox proportional risk regression model analysis showed that age>65 years old (HR=4.017, 95%CI: 1.468-10.992, P=0.007) was a risk factor for PFS in NSCLC patients who received immunotherapy combined with chemotherapy and bevacizumab after EGFR-TKIs treatment failure. Moderate expression of PD-L1 (HR=0.360, 95%CI: 0.139-0.930, P=0.035) and high expression of PD-L1 (HR=0.155, 95%CI: 0.039-0.625, P=0.009) were protective factors for PFS. Most of the treatment-related adverse reactions in the whole group were grade 1-2, including bone marrow suppression (n=24), nausea (n=25), decreased appetite (n=24), fatigue (n=22), vomiting (n=18), abnormal liver function (n=17), blood creatinine increased (n=10), and so on. These were tolerated by the patients. Conclusions: NSCLC patients who failed EGFR-TKIs treatment can tolerate adverse reactions related to immunotherapy combined with chemotherapy and bevacizumab treatment. PFS is significantly prolonged in those aged≤65 years and those with moderate and high expression of PD-L1.