对于接受奥西美替尼治疗的非小细胞肺癌（NSCLC）患者的治疗失败模式和随后的治疗方案了解甚少。我们分析了奥西美替尼治疗期间的疾病进展，以确定潜在的治疗策略。从电子记录中找到了2014年6月至2018年11月之间出现前一代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗失败的晚期NSCLC患者进行了分析。分析了患者的肿瘤特征、疗效结果、影响器官的放射学研究以及奥西美替尼前后的治疗方式。共纳入84名患者。在奥西美替尼开始治疗时，骨骼（50.0%）和脑部（41.9%）是最常见的单一转移部位，而在奥西美替尼疾病进展期间，胸部受累（73.3%）比骨骼（27.4%）或脑部（20.2%）转移更为频繁。观察到15名患者（17.9%）出现寡进展性疾病（PD）和3名患者（3.6%）出现中枢神经系统（CNS）庇护区PD。大多数无脑部转移病灶的患者在奥西美替尼开始治疗时仍保持无脑部转移病灶（46/49，93.9%），而60%的患者（21/35）在存在颅内疾病进展的情况下仍表现出颅内疾病控制。对23名患者（27.4%）探讨了对奥西美替尼的耐药机制，其中14名患者（60.9%）出现T790M丢失，与未出现T790M丢失的患者（进展生存期5.4个月vs. 16.5个月，p=0.02;总生存期未达到p=0.03）相比有更差的生存结局。在奥西美替尼治疗期间，PD更倾向于发生在胸部和已有的病灶部位。无论基线的颅内转移病灶和之前的颅部放疗如何，颅外PD均优于颅内PD。这些结果支持奥西美替尼的颅内疗效，并可指导EGFR突变NSCLC合并颅内转移病灶的治疗策略。© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Patterns of treatment failure and subsequent treatment in non-small cell lung cancer (NSCLC) patients treated with osimertinib are scarcely known. We analyzed the disease progression during osimertinib treatment to identify potential treatment strategies.We identified advanced NSCLC patients who commenced osimertinib treatment after progression on previous epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) from June 2014 to November 2018 from electronic records. Patients' tumor characteristics, efficacy outcomes, affected organs from radiology studies, and treatment modalities before and after osimertinib were analyzed.Eighty-four patients were included. At osimertinib initiation, bone (50.0%) and brain (41.9%) were the commonest single metastatic sites, whereas thoracic involvement (73.3%) was more frequent than bone (27.4%) or brain (20.2%) metastasis during disease progression on osimertinib. Oligo-progressive disease (PD) and central nervous system (CNS)-sanctuary PD were observed in 15 (17.9%) and 3 (3.6%) patients, respectively. Most patients without brain metastasis (BM) at osimertinib initiation remained BM-free (46/49, 93.9%), and 60% of patients (21/35) with pre-existing BM showed intracranial disease control despite extracranial PD. The resistance mechanisms to osimertinib were explored in 23 patients (27.4%), and T790M-loss was observed in 14 patients (60.9%) who had worse survival outcomes than those without T790M-loss (progression-free survival, 5.4 vs. 16.5 months, p = 0.02; overall survival, not reached, p = 0.03).PD during osimertinib treatment occurred preferentially in the thorax and pre-existing sites. Extracranial PD prevailed over intracranial PD regardless of baseline BM and prior brain radiation. These results support osimertinib's intracranial efficacy and may guide treatment strategies for EGFR-mutated NSCLC with BM.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.