EGFR罕见突变致奥希替尼耐药的晚期肺腺癌1例并文献复习

Osimertinib-resistant advanced lung adenocarcinoma caused by rare EGFR mutation:a case report and literature review

目的探索二代测序(NGS)技术在监测罕见耐药位点并指导晚期肺腺癌患者治疗中的应用。方法选取2016年9月来中南医院就诊的1例晚期肺腺癌患者,采用NGS技术监测该患者二线奥希替尼治疗进展后基因突变情况,分析病例资料回顾治疗过程,并对现有的相关文献进行复习总结。结果本例晚期肺腺癌患者初诊时携带EGFR-L858R敏感突变,一线吉非替尼靶向治疗后继发T790M突变。经奥希替尼靶向治疗再次进展后行NGS检测,首次发现罕见的EGFR T790M-G796S-L858R和T790M-G796del-L858R双克隆复合耐药突变,治疗方案调整为双药化疗+贝伐单抗,患者目前病情稳定。结论奥希替尼耐药机制多样,临床处理困难,再次活检、重复血液基因分子分型是了解耐药机制及指导后续治疗的关键,而NGS技术因其独特的优势在晚期肺腺癌患者耐药监测及全程管理中起着重要作用。

Objection To explore the application of NGS technology in monitoring rare resistance mutation and guiding the treatment of advanced NSCLC patient.Method A patient with advanced lung adenocarcinoma who came to Zhongnan Hospital in September 2016 was selected.NGS technology was used to monitor the gene mutation status of the patient after the second line osimertinib treatment progress.The case data was analyzed to review the treatment process,and the existing relevant literature Review summary.Result The patient was initially diagnosed as advanced NSCLC with EGFR-L858R sensitive mutation.After first line gefitinib targeted treatment,she was detected with secondary T790M mutation from cfDNA in plasma.NGS detection was performed after progression again,finding a rare EGFR T790M-G796S-L858R and T790M-G796del-L858R double clone resistance mutations for the first time.The treatment scheme was adjusted to dualdrug chemotherapy+bevacizumab,and she is now in stable condition.Conclusion The resistance mechanism of Osimertinib is diverse and the clinical treatment is difficult.Secondary biopsy and repeated blood molecular typing are the key to understand the resistance mechanism and guide the follow-up treatment.Because of its unique advantages,NGS technology plays an important role in resistance monitoring and whole process management of patients with advanced lung adenocarcinoma.