Background
NSCLC, death, malignant lung tumors, NSCLCs, EGFR-mutant NSCLC, cancer, anaplastic lymphoma
CANCER, NSCLC, NON-SMALL CELL LUNG CANCER
Non-small cell lung cancer (NSCLC), the leading cause of death (85-90%) among all malignant lung tumors, is generally related to smoking and more prominent in individuals with advanced age (65-year-old or above). Several oncogenic driver mutations, e.g., epidermal growth factor receptor (EGFR; 15–20% of NSCLCs) and anaplastic lymphoma kinase (ALK; 5% of NSCLCs), have been shown to promote cell transformation and cancer growth and progression [Although osimertinib, a third-generation EGFR TKI, has superior efficacy as the first-line treatment based on the FLAURA study, its efficacy against concurrent mutations is still unclear. Recently, the LC-SCRUM study showed that the median PFS of osimertinib for EGFR-mutant NSCLC with concomitant amplification of RTK-related genes and cell cycle genes was approximately 8 months shorter than that of the FLAURA study [The molecular mechanism of vascular endothelial growth factor (VEGF) inhibitors combined with EGFR inhibitors in the treatment of NSCLC suggests synergistic anti-tumor effects and drug resistance alleviation. In recently reported large-scale randomized studies including JO25567 [Anlotinib selectively suppresses VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β, and is the first and only effective single-agent vascular-targeted drug for advanced NSCLC [Here, we report the efficacy and safety of a prospective multicenter trial evaluating a new combination regimen, anlotinib plus icotinib, as the first-line treatment of EGFR mutation-positive advanced NSCLC. More importantly, we evaluated the relationship between efficacy and genetic profile of this new regimen in the treatment of patients with EGFR-sensitizing mutations harboring concurrent mutations, in order to identify the population that would most benefit from this combination regimen.