NGS-Based ctDNA Profiling After the Resistance of Second-Line Osimertinib for Patient with EGFR-Mutated Pulmonary Adenocarcinoma

Dan Li,1,* DaFu Yang,1,* SaiQiong Cui,1 Evenki Pan,2 Peng Yang,2 ZhaoXia Dai1 1The Second Department of Thoracic Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: ZhaoXia DaiThe Second Department of Thoracic Medical Oncology, The Second Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, Liaoning, People’s Republic of ChinaTel +8617709873617Email daizhaoxia@dmu.edu.cnAbstract: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is effective in EGFR T790M positive non-small-cell lung cancer (NSCLC). Despite the efficacy of osimertinib, patients inevitably develop resistance and the mechanisms of osimertinib resistance are heterogeneous. Here, we report that a lung adenocarcinoma patient with EGFR L858R mutation who was treated with second-line osimertinib therapy acquired multiple resistance to osimertinib by the non-invasive circulating tumor DNA (ctDNA) genotyping. This case provides the possible mechanisms of osimertinib resistance that occur during the disease progression and supports the longitudinal monitoring of ctDNA for the detection of novel acquired resistance and tumor heterogeneity.Keywords: osimertinib, acquired resistance, EGFR mutation, lung adenocarcinoma, circulating tumor DN