Adjuvant targeted therapy in high-risk stage IB epidermal growth factor receptor-mutant lung cancer: Role of ground-glass opacity components.

Objective: The necessity of adjuvant targeted therapy in stage IB epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) remains controversial. We aimed to evaluate the efficacy of adjuvant EGFR tyrosine kinase inhibitors in patients with high-risk pathologic features and sought to explore potential subgroups that may derive benefit. Methods: This study reviewed patients with pathologic-stage IB EGFR-mutant NSCLC and high-risk factors between 2018 and 2020. Propensity score matching was used to match patients who received adjuvant EGFR tyrosine kinase inhibitors (adjuvant targeted therapy, or ATT) with those who did not (non-ATT). Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results: A total of 361 patients were included, of whom 41 received ATT and 320 did not. The median follow-up was 63.6 months. In the overall cohort, post-matched DFS (hazard ratio [HR], 0.60; 95% CI, 0.31-1.17) and OS (HR, 1.06; 95% CI, 0.41-2.71) did not differ between the ATT and non-ATT groups. Multivariable analysis identified the presence of a ground-glass opacity component as a favorable prognostic factor. Subsequent subgroup analyses demonstrated that ATT significantly prolonged DFS in patients with pure-solid tumors (HR, 0.33; 95% CI, 0.12-0.92), but not OS (HR, 0.55; 95% CI, 0.13-2.28). In contrast, ATT was not associated with improved DFS or OS in patients with part-solid tumors. Conclusions: Adjuvant targeted therapy did not improve long-term survival in stage IB EGFR-mutant NSCLC with high-risk features, although it prolonged DFS in pure-solid tumors. A de-escalation strategy may be considered for postoperative management, particularly in part-solid tumors.