The Compound Mutations in Chinese Advanced Non-small Cell Lung Cancer Patients

Literatures regarding the prevalence and clinical significance of compound EGFR mutations are limited. Until now, none of retrospective or prospective research has focused on compound mutations except case reports. In this study, we screened a cohort of 3,000 treatment-naïve Chinese advanced NSCLC patients using capture-based ultra-deep targeted sequencing to evaluate the prevalence of compound mutations and the efficacy of EGFR-TKI in this population. Of the 3,000 patients screened, 1,266 (42.2%) had mutation; among them, 15 patients (1.2%) harborin compound mutations, with 10 patients carrying L858R in combination with a rare mutation and five patients carrying two rare mutations. No patient with 19del was observed. Interestingly, no configuration was identified in this cohort. All of the patients harborin compound mutations were non-smokers, histologically diagnosed with adenocarcinoma and received first-generation EGFR-TKI. Furthermore, our data also revealed that patients with compound mutations exhibit comparable PFS to first generation EGFR-TKI comparing to patients with single activating mutation. This observation was further supported by molecular modeling analyses which demonstrated compound mutations do not alter the ATP-binding pocket of , thus having no effect on the interaction between gefitinib and .