Association between adjuvant EGFR-TKI therapy and survival outcomes in completely resected stage I invasive lung adenocarcinoma (≤3 cm) with sensitizing EGFR mutations and pathological high-risk features
Year: 2026
Type: article
Abstract: Background: Adjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy improves prognosis in patients with resected EGFR-mutated non-small cell lung cancer. However, evidence supporting its use in stage I disease with pathological high-risk features remains limited. We evaluated the association between adjuvant EGFR-TKI therapy and survival outcomes in patients with completely resected stage I invasive lung adenocarcinoma (LUAD) (≤3 cm), sensitizing EGFR mutations, and pathological high-risk features. Methods: This retrospective cohort study included patients who underwent complete resection for stage I invasive LUAD (≤3 cm) between January 2011 and May 2024. Eligible patients had an EGFR exon 19 deletion or exon 21 L858R mutation and at least one pathological high-risk feature, including lymphovascular invasion, visceral pleural invasion, spread through air spaces, high-grade histologic patterns (micropapillary, solid, and complex glandular patterns), or poor differentiation. The study outcomes were relapse-free survival (RFS) and overall survival (OS). The primary analysis used a 90-day landmark design, with baseline differences addressed using stabilized inverse probability of treatment weighting (IPTW). Survival distributions were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Simon-Makuch curves and time-dependent Cox regression analysis were additionally used to account for changes in treatment exposure over time. A 120-day landmark analysis was performed as a sensitivity analysis. Results: Among 357 eligible patients, 354 remained alive and relapse-free at the 90-day landmark. Of these, 104 had initiated adjuvant EGFR-TKI therapy by the landmark, whereas 250 had not. In the unweighted landmark analysis, adjuvant EGFR-TKI therapy was associated with improved RFS (P=0.004; HR =0.27, 95% CI: 0.13-0.56). This association remained significant after IPTW adjustment (P=0.009; HR =0.28, 95% CI: 0.11-0.68). No significant difference in OS was observed in either the unweighted analysis (P=0.91; HR =0.93, 95% CI: 0.33-2.63) or the IPTW-weighted analysis (P=0.38; HR =1.34, 95% CI: 0.50-3.61). In the time-dependent analysis, EGFR-TKI exposure was associated with a lower hazard of relapse (P<0.001; HR =0.27, 95% CI: 0.14-0.52) but not with OS (P=0.49; HR =1.14, 95% CI: 0.41-3.19). The 120-day landmark sensitivity analysis yielded consistent results. Conclusions: In patients with completely resected stage I invasive LUAD (≤3 cm), sensitizing EGFR mutations, and pathological high-risk features, adjuvant EGFR-TKI therapy was associated with improved RFS, whereas no significant association with OS was observed.
Institutions: Sichuan University, West China Hospital of Sichuan University
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7221193562