Work

Neoadjuvant EGFR-TKI with or without Platinum-Based Chemotherapy for Stage II–III EGFR-Mutant Non–Small-Cell Lung Cancer: A Multicenter Retrospective Cohort Study

Year: 2026

Type: preprint

Abstract: Background The surgical outcomes and toxicity of neoadjuvant EGFR tyrosine kinase inhibitor (TKI) monotherapy versus TKI plus platinum-based chemotherapy remain uncertain in routine care for EGFR-mutant non–small-cell lung cancer (NSCLC). Methods This multicenter retrospective cohort study included 158 patients with stage II–III NSCLC harboring a sensitizing EGFR mutation who initiated neoadjuvant therapy and planned curative-intent surgery (EGFR-TKI, n = 94; EGFR-TKI+platinum-based chemotherapy, n = 64). The primary endpoint was R0-ITT (R0 resection among all treatment initiators), with patients not undergoing surgery counted as failures. Overlap weighting was used to balance pretreatment covariates. Results Stage III disease accounted for 63.8% and 93.8% of the monotherapy and combination groups, respectively. After weighting, R0-ITT rates were 70.3% and 87.2%, respectively (risk difference [RD] 16.9 percentage points; 95% confidence interval [CI], 2.9 to 31.1). Surgery completion was higher with combination therapy (RD 17.9; 95% CI, 5.1 to 32.3), and disease-related failure to undergo surgery was lower (RD − 16.1; 95% CI, − 28.4 to − 4.5). For major pathologic response among all treatment initiators (ITT-MPR), the weighted RD was 6.5 percentage points (95% CI, − 7.1 to 20.1). Among patients with evaluable surgical specimens, MPR rates were similar (15.3% vs. 16.1%). Grade ≥ 3 adverse events (AEs) were more frequent with combination therapy (RD 14.2; 95% CI, 2.5 to 26.4). Conclusions Combination therapy was associated with higher R0-ITT and surgery completion rates and more grade ≥ 3 AEs. Pathologic response rates among patients with evaluable surgical specimens were similar. Treatment-selection bias may persist after weighting; prospective studies are needed.

Source: Research Square

DOI: 10.21203/rs.3.rs-11237456/v1