EGFR突变是肺腺癌基因改变的最重要驱动因素,对EGFR-TKIs敏感。然而,EGFR-TKIs耐药在大多数EGFR突变的肺癌患者中是不可避免的.迄今为止,已经揭示了许多抗性机制,更多的人仍在调查中。由于选择的压力,耐药后可能存在肿瘤内异质性,尤其是在多行治疗后的患者。对那些病人来说,重要的是选择针对肿瘤主干/主要克隆的治疗方法,以实现最佳的临床获益.这里,我们将报道一个EGFR突变的肺腺癌患者,其耐药机制包括EGFR扩增的异质性,RB1的大片段缺失,以及靶向治疗后的组织学转变。在我们的案例中,根据液体活检监测和组织活检的下一代测序(NGS)结果,EGFR扩增似乎是耐药机制的主要克隆。考虑到高EGFR扩增水平,患者接受EGFR-TKI联合尼妥珠单抗联合治疗,抗EGFR单克隆抗体(mAb),取得了一定的临床效益。我们的案例揭示了EGFR突变患者EGFR扩增的治疗,并表明EGFR-TKI与抗EGFRmAb的组合可能是基于基因测试的可能治疗选择之一。此外,治疗方法的决定应关注肿瘤的主要克隆,并应根据治疗过程中遗传特征的动态变化进行及时调整。
EGFR mutations are the most important drivers of gene alterations in lung adenocarcinomas and are sensitive to EGFR-TKIs. However, resistance to EGFR-TKIs is inevitable in the majority of EGFR-mutated lung cancer patients. Numerous resistant mechanisms have been revealed to date, and more are still under investigation. Owing to the selective pressure, intratumoral heterogeneity may exist after resistance, especially in patients after multiple lines of treatment. For those patients, it is important to choose therapies focused on the trunk/major clone of the tumor in order to achieve optimal clinical benefit. Here, we will report an EGFR-mutated lung adenocarcinoma patient with heterogeneity of resistant mechanisms including EGFR amplification, large fragment deletion of RB1, and histological transformations after targeted treatments. In our
case, EGFR amplification seemed to be the major clone of the resistant mechanism according to the next-generation sequencing (NGS) results of both liquid biopsy monitoring and tissue biopsies. In consideration of the high EGFR amplification level, the patient was administered by combination treatment with EGFR-TKI plus nimotuzumab, an anti-EGFR monoclonal antibody (mAb), and achieved a certain degree of clinical benefit. Our
case sheds light on the treatment of EGFR-mutant patients with EGFR amplification and indicates that a combination of EGFR-TKI with anti-EGFR mAb might be one of the possible treatment options based on genetic tests. Moreover, the decision on therapeutic approaches should focus on the major clone of the tumor and should make timely adjustments according to the dynamic changes of genetic characteristics during treatment.