Association of Delayed Adjuvant Targeted Therapy With Recurrence Risk in Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Multicenter Real-World Study

Introduction Adjuvant targeted therapy is standard of care for resected EGFR-mutant NSCLC, but the clinical relevance of treatment timing remains poorly defined. This study aimed to assess real-world practice patterns of adjuvant targeted therapy and their association with recurrence risks in resected EGFR-mutant NSCLC. Methods We identified patients with completely resected stage IB-IIIB EGFR-mutant NSCLC from two Chinese centers and a US database between January 2020 and December 2023. Disease-free survival (DFS) was compared using log-rank test and restricted mean survival time (RMST) analysis. Multivariable regression models and inverse probability of treatment weighting were used to adjust for covariates. The threshold for delayed treatment initiation was estimated using restricted cubic splines. Results A total of 707 patients were included. Of them, 67% (n=472) received adjuvant targeted therapy with or without chemotherapy. Adding chemotherapy showed a trend toward improved DFS versus adjuvant targeted therapy alone (HR=0.70, 95%CI 0.27 to 1.82, P =0.466). Among patients receiving targeted therapy alone, delayed treatment initiation (>48 days post-surgery) was independently associated with shorter DFS (adjusted RMSTD=-6.44 months [95% CI, -12.27 to -0.60], P =0.031), consistently across examined subgroups. By contrast, among patients receiving targeted therapy plus chemotherapy, delayed initiation of either modality did not significantly compromise outcomes. Conclusions Among patients receiving adjuvant targeted therapy without chemotherapy, later initiation of adjuvant TKI was associated with shorter DFS, with a data-derived cutoff of 48 days. Although the timing threshold requires further validation, these findings support timely initiation of adjuvant TKI when clinically feasible.