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.
目的： 探讨表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗失败非小细胞肺癌（NSCLC）患者采用免疫联合化疗及贝伐珠单抗治疗的疗效及其影响因素。 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月收治的60例免疫联合化疗及贝伐珠单抗治疗EGFR-TKIs治疗失败NSCLC患者的临床资料。采用电话或门诊复查的方式对患者进行随访，随访截至2022年10月1日，中位随访8.2（95%CI：7.1~9.3）个月，60例患者均获得随访。应用实体瘤的疗效评价标准进行近期疗效评价，根据不良事件通用术语标准评价患者不良反应。以Kaplan-Meier法绘制生存曲线，采用Cox比例风险回归模型分析无进展生存时间（PFS）的影响因素。 结果： 60例NSCLC患者中，男22例；年龄41~75岁，中位年龄61岁。部分缓解11例，疾病稳定19例，疾病进展30例。中位PFS为8.2（95%CI：7.2~9.2）个月，其中程序性细胞死亡受体配体1（PD-L1）低表达［肿瘤细胞阳性比（TPS）<1%］、PD-L1中表达（1%≤TPS≤49%）、PD-L1高表达（TPS≥50%）组患者的中位PFS分别为6.4（95%CI：4.8~8.0）、8.3（95%CI：7.3~9.3）和10.6（95%CI：7.1~14.1）个月，差异有统计学意义（χ2=13.58，P<0.001）。多因素Cox比例风险回归模型分析结果显示，年龄>65岁（HR=4.017，95%CI：1.468~10.992，P=0.007）是接受免疫联合化疗及贝伐珠单抗治疗EGFR-TKIs治疗失败NSCLC患者PFS的危险因素，而PD-L1中表达（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）是接受免疫联合化疗及贝伐珠单抗治疗EGFR-TKIs治疗失败NSCLC患者PFS的保护因素。治疗相关不良反应主要为1~2级，包括骨髓抑制（24例）、恶心（25例）、食欲下降（24例）、乏力（22例）、呕吐（18例）、肝功能异常（17例）、血肌酐升高（10例）等，患者可耐受。 结论： EGFR-TKIs治疗失败的NSCLC患者接受免疫联合化疗及贝伐珠单抗治疗的相关不良反应可耐受，年龄≤65岁以及PD-L1中、高表达者的PFS明显延长。.