Heterogeneity of Resistant Mechanisms in an -TKI Relapsed Patient with Amplification and Response to Nimotuzumab: A Case Report

mutations are the most important drivers of gene alterations in lung adenocarcinomas and are sensitive to -TKIs. However, resistance to -TKIs is inevitable in the majority of -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 -mutated lung adenocarcinoma patient with heterogeneity of resistant mechanisms including amplification, large fragment deletion of , and histological transformations after targeted treatments. In our case, 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 amplification level, the patient was administered by combination treatment with -TKI plus nimotuzumab, an anti- monoclonal antibody (mAb), and achieved a certain degree of clinical benefit. Our case sheds light on the treatment of -mutant patients with amplification and indicates that a combination of -TKI with anti- 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.