Retrospective study on the clinicogenomic characteristics of EGFR mutant and wildtype NSCLC

Background Lung cancer is among the leading causes of mortality. Nearly 90% of all lung cancers are histologically classified as non-small cell lung cancer (NSCLC). A subset of these tumors harbor mutations on the epidermal growth factor receptor gene ( EGFR ) and such patients are candidates for targeted therapy with EGFR tyrosine kinase inhibitors (EGFR TKIs). Aim To compare and contrast the clinicogenomic characteristics of EGFR mutant and wildtype NSCLC. Methods and results A retrospective cohort study design was used to analyze publicly available data on cBioPortal.org. Patients with EGFR mutations were more likely to be female, of Asian ethnicity, never-smokers, and diagnosed with lung adenocarcinoma. Metastasis to the pleura, pleural fluid, and liver were common in patients with EGFR mutant NSCLC. On the other hand, lymph node, brain and adrenal gland metastases were more common in patients with other mutations. While the median overall survival was about the same in the two groups, progression free survival was significantly shorter in the EGFR mutant group. The mutational landscape was significantly different in the two groups with EGFR mutant NSCLCs having a lower mutational burden. Differences in copy number alterations between the two groups were also noted. Conclusions The clinicogenomic profiles of EGFR mutant and EGFR wildtype significantly differ. Further studies on these differences and underlying mechanisms are likely to lead to new “druggable” targets that overcome EGFR TKI resistance.