肺癌是全球最常见的癌症相关死因，其中大部分为非小细胞肺癌（NSCLC）。表皮生长因子受体（EGFR）突变是NSCLC的常见驱动因素。NSCLC，特别是腺癌的治疗方案在很大程度上依赖于特定可操作的驱动突变的存在或缺失。液体活检可以指导治疗方案，以检测各种抵抗治疗的机制的存在。我们报告了三例NSCLC EGFR突变病例，每例均采用Osimertinib与联合治疗方案来对抗抵抗机制。第一位患者同时患有EGFR L858R/L833V复合突变，MET放大和CEP85L-ROS1融合基因，第二位患者患有EGFR外显子19缺失和MKRN1-BRAF融合基因，最后一位患者患有EGFR L858R/V834L复合突变，MET放大。每种方案都使用了酪氨酸激酶抑制剂或单克隆抗体，以及Osimertinib，并允许快速和相对持久的治疗反应。版权所有 © 2023 Kian, Krayim, Alsana, Giles, Purim, Alguayn, Alguayn, Peled and Roisman。

Lung cancer is the most common cancer-related cause of death worldwide, most of which are non-small cell lung cancers (NSCLC). Epidermal growth factor receptor (EGFR) mutations are common drivers of NSCLC. Treatment plans for NSCLC, specifically adenocarcinomas, rely heavily on the presence or absence of specific actionable driver mutations. Liquid biopsy can guide the treatment protocol to detect the presence of various mechanisms of resistance to treatment. We report three NSCLC EGFR mutated cases, each treated with Osimertinib in a combination therapy regimen to combat resistance mechanisms. The first patient presented with EGFR L858R/L833V compound mutation with MET amplification alongside CEP85L-ROS1 fusion gene, the second with EGFR exon 19del and MKRN1-BRAF fusion, and the last EGFR L858R/V834L compound mutation with MET amplification. Each regimen utilized a tyrosine kinase inhibitor or monoclonal antibody in addition to osimertinib and allowed for a prompt and relatively durable treatment response.Copyright © 2023 Kian, Krayim, Alsana, Giles, Purim, Alguayn, Alguayn, Peled and Roisman.