Baseline predictors of early progression during EGFR-TKI therapy in patients with EGFR-mutant non-small cell lung cancer: A retrospective cohort study

This single-center retrospective cohort study investigated baseline clinical, molecular, and treatment-related factors associated with early progression among patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer receiving EGFR tyrosine kinase inhibitors (EGFR-TKIs) between June 2022 and June 2025. Eligible patients treated during the study period were consecutively screened according to predefined eligibility criteria, and all eligible patients were included without case-control matching. Early progression was defined a priori as progressive disease within 6 months after EGFR-TKI initiation according to response evaluation criteria in solid tumors version 1.1; this cutoff was selected as a clinically meaningful landmark for early treatment failure/primary resistance and to distinguish rapid failure from patients achieving at least short-term disease control. A total of 156 patients were included (early progression, n = 52; nonearly progression, n = 104). Compared with nonearly progression, early progression was characterized by a different smoking distribution, lower body mass index, higher prevalence of chronic obstructive pulmonary disease, and greater baseline tumor burden as reflected by a higher number of target lesions, as well as higher rates of liver metastasis, bone metastasis, and pleural effusion. Molecular and treatment profiling showed higher frequencies of TP53 co-mutation and baseline EGFR T790M in early progressors, together with a higher proportion of first-generation EGFR-TKI use and more frequent receipt of EGFR-TKI as second-line or later therapy. In multivariable logistic regression, current smoking, lower body mass index, higher target lesion count, liver metastasis, bone metastasis, pleural effusion, second-line or later EGFR-TKI use, first-generation EGFR-TKI exposure, and mesenchymal–epithelial transition factor amplification were independently associated with early progression, while baseline EGFR T790M showed a borderline association. These findings support risk-adapted monitoring and molecularly informed management strategies in EGFR-mutant non-small cell lung cancer.