中医益气养阴解毒方案联合安罗替尼治疗晚期非小细胞肺癌的疗效与安全性分析

Efficacy and safety of Yiqi Yangyin Jiedu regimen plus anlotinib in the treatment of advanced non-small cell lung cancer

目的研究中医益气养阴解毒方案联合安罗替尼治疗晚期非小细胞肺癌(NSCLC)的疗效与安全性。方法采用回顾性研究方法,通过电子病历系统收集2018年6月至2021年3月接受中医益气养阴解毒方案联合安罗替尼治疗的晚期NSCLC病例资料,所有病例随访至2021年11月1日,记录驱动基因、既往治疗情况、病理类型等一般资料,评价实体瘤疗效,分析美国东部肿瘤协作组(ECOG)活动状态评分的变化和不良反应的发生情况,Kaplan-Meier法计算中位无进展生存时间(PFS)和中位总生存时间(OS),Cox多因素分析研究PFS、OS的影响因素。结果①共纳入33例接受中医益气养阴解毒方案联合安罗替尼治疗的晚期NSCLC病例,其中12例携带驱动基因,所有患者既往均经表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)、间变性淋巴瘤激酶酪氨酸激酶抑制剂(ALK-TKI)或化疗一线和二线治疗后耐药,其中20例患者接受过2个或2个以上化疗方案后发生疾病进展;安罗替尼的中位治疗线数为三线。②33例病例的中位PFS为7个月[95%CI(2.7~11.3)],中位OS为16个月[95%CI(12.4~19.6)]。③实体瘤最佳疗效中,部分缓解3例、稳定29例、疾病进展1例,客观缓解率为9.1%,疾病控制率为97.0%。④治疗过程中,仅1例患者发生3级不良反应(肾功能不全),并因此减量服用安罗替尼。⑤治疗过程中,22例(66.7%)患者的ECOG活动状态评分保持稳定。⑥Cox多因素分析结果显示,治疗后促甲状腺激素(TSH)升高与更长的PFS显著相关[RR=3.971,95%CI(1.524~10.347),P=0.005],未发现与OS相关的独立预后因素;治疗后TSH升高患者的中位PFS为12个月,长于TSH未升高的患者(中位PFS为5个月)[RR=0.197,95%CI(0.067~0.574),P=0.0029]。结论中医益气养阴解毒方案或可通过减轻安罗替尼的不良反应、维持一般体力状况来延长晚期NSCLC患者的生存时间。

Objective To evaluate the efficacy and safety of Yiqi Yangyin Jiedu(YQYYJD)regimen of traditional Chinese medicine(TCM)plus anlotinib for advanced non-small cell lung cancer(NSCLC).Methods A retrospective study approach was applied to collect information on advanced NSCLC cases treated with the YQYYJD regimen of TCM plus anlotinib from June 2018 to March 2021 through the electronic medical record system.All cases were followed up until November 1,2021,and general information such as driver gene mutation,previous treatment,and pathological types were recorded to evaluate the outcome of solid tumors,and changes in Eastern Cooperative Oncology Group(ECOG)score and the incidence of adverse events were analyzed.Median progression free survival(PFS)and median overall survival(OS)were calculated by the Kaplan-Meier method.Cox analysis was used to evaluate the significance of factors influencing PFS and OS.Results①A total of 33 cases of advanced NSCLC treated with YQYYJD regimen of TCM plus anlotinib were included in the study,and 12 cases harbored driver gene mutation.All patients had previously received epithelial growth factor receptor tyrosine kinase inhibitor(EGFR-TKI),anaplastic lymphoma kinase tyrosine kinase inhibitors(ALK-TKI),or first-and second-line chemotherapy,and acquired resistance,and 20 patients progressed after at least two lines of chemotherapy.The median line of therapy for anlotinib was three.②The median progression free survival(PFS)was 7.0 months(95%CI:2.7-11.3),and the median overall survival(mOS)was 16.0 months(95%CI:12.4-19.6)in 33 cases.③In evaluating best outcomes of solid tumors,there were 3 cases of partial response,29 cases of stable disease,and 1 case of disease progression,with an objective response rate of 9.1%and a disease control rate of 97.0%.④During the treatment,only 1 case of grade 3 treatmentrelated adverse effects(renal impairment)and reduced dose of anlotinib was reported.⑤During the course of treatment 22 cases(66.7%)reported stable performance status.⑥Cox multifactorial analysis demonstrated that elevated TSH level after treatment was significantly associated with longer PFS(RR=3.971,95%CI:1.524-10.347,P=0.005),and no independent prognostic factors related to OS was found;The mPFS of patients with elevated TSH after treatment was 12 months,longer than that of patients without elevated TSH(mPFS was 5 months)(RR=0.197,95%CI:0.067-0.574,P=0.0029).Conclusion YQYYJD regimen of TCM may prolong survival of advanced NSCLC patients by reducing adverse effects of anlotinib and stabilizing general performance status.