奥希替尼联合贝伐珠单抗在获得性EGFR T790M突变晚期非小细胞肺癌的疗效分析

Efficacy of Osimertinib Combined with Bevacizumab in Advanced Non-small Cell Lung Cancer Patients with Acquired EGFR T790M Mutation

背景与目的奥希替尼是对表皮生长因子受体(epidermal growth factor receptor,EGFR)T790M突变非小细胞肺癌(non-small cell lung cancer,NSCLC)有效的第三代靶向药物。尽管第一代EGFR酪氨酸激酶抑制剂(EGFRtyrosine kinase inhibitors,EGFR-TKIs)联合贝伐珠单抗治疗可延长无进展生存期(progression-free survival,PFS),但奥希替尼联合贝伐珠单抗的后线疗效在II期研究WJOG8715L中并未得到肯定,目前该联合模式在中国人群中的数据仍非常有限。本研究旨在分析真实世界中奥希替尼联合贝伐珠单抗二线治疗的疗效,评价奥希替尼联合抗血管治疗模式在EGFR T790M获得性耐药突变NSCLC中的二线治疗价值。方法收集2020年1月-2021年8月收治的第一、二代EGFR-TKIs治疗后伴EGFR T790M突变NSCLC患者共42例。16例接受二线奥希替尼联合贝伐珠单抗治疗,另26例接受二线奥希替尼单药治疗。分析患者的治疗效果。结果联合组和单药组客观缓解率(objective response rate,ORR)相当(43.8%vs 50.0%,P=0.694)。两组中位PFS(14.0个月vs 13.0个月,P=0.797)和总生存期(overall survival,OS)(29.0个月vs 26.0个月,P=0.544)均未见统计学差异。Cox回归模型显示前线联合贝伐珠单抗治疗是奥希替尼后线单药或联合治疗PFS(P=0.045)及OS(P=0.023)更短的独立预测因素。结论奥希替尼联合贝伐珠单抗二线治疗相比靶向单药治疗未见更好的疗效。

Background and objective Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)capable of overcoming non-small cell lung cancer(NSCLC)with EGFR T790M mutation.Al-st though the addition of bevacizumab to 1 generation EGFR-TKIs confers a significant improvement in progression-free survival(PFS)in treatment-naive EGFR mutant NSCLC patients,osimertinib plus bevacizumab combination failed to show prolongation in the phase 2 study WJOG8715L.Data of such combination in Chinese patients are still lacking.This study aimed to explore the efficacy of the addition of bevacizumab to osimertinib as second-line therapy in real-world data,and to evaluate the role of anti-angiogenesis plus osimertinib combination therapeutic strategies in pretreated Chinese NSCLC patients with acquired EGFR T790M mutation.Methods A total of 42 advanced NSCLC patients with acquired EGFR T790M mutation after prior EGFR-TKIs treatment were collected between January 2020 to August 2021,with 16 cases treated with osimertinib plus bevacizumab and 26 cases treated with osimertinib.The treatment effect of patients were analyzed.Results The objective response rate(ORR)in combination group and osimertinib group were 43.8%and 50.0%respectively(P=0.694).No statistically significant difference in median PFS(14.0 mon vs 13.0 mon,P=0.797)and overall survival(OS)(29.0 mon vs 26.0 mon,P=0.544)between the com-bination group and osimertinib group were observed.Prior history of bevacizumab was identified as an independent predictor of PFS(P=0.045)and OS(P=0.023).Conclusion Our study demonstrated that adding bevacizumab to osimertinib could not show advantages in PFS and OS in pretreated NSCLC patients harboring EGFR T790M-mutation.