Adjuvant chemotherapy with or without EGFR-TKIs for resected EGFR-mutated non-small cell lung cancer: a pooled analysis of four randomized controlled trials

Background: The role of adding adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to chemotherapy (ETC) among patients with completely resected EGFR-mutated non-small cell lung cancer (NSCLC) remains unclear, particularly with respect to overall survival (OS). A meta-analysis was performed using randomized controlled trials (RCTs), aiming to assess both efficacy and safety profiles of adjuvant chemotherapy plus EGFR-TKIs versus chemotherapy alone. Methods: Six databases were systematically screened to retrieve eligible RCTs evaluating ETC versus placebo plus chemotherapy (PC) as adjuvant therapy. Overall survival (OS) and disease-free survival (DFS) were defined as the primary endpoints, while disease relapse together with treatment-related adverse events (TRAEs) constituted the secondary endpoints. Results: A total of five RCTs comprising 890 patients were included. Baseline patient characteristics (e.g., age, sex, and disease stage) were comparable between groups. ETC significantly improved OS (HR: 0.56 [0.41, 0.77], P = 0.0003) and DFS (HR: 0.36 [0.23, 0.57], P < 0.0001), with consistent benefits observed across all predefined subgroups. OS rates at 30–60 months and DFS rates at 6–60 months were significantly higher in the ETC group. More tumor recurrences were found in the PC group (RR: 0.37 [0.21, 0.66], P = 0.0007), predominantly due to distant metastases. TRAEs (RR: 1.35 [1.05, 1.73], P = 0.02) and TRAE-related treatment discontinuation or dose reduction (RR: 5.00 [1.12, 22.28], P = 0.03) were more frequent in the ETC group. Conclusions: Adjuvant ETC significantly improves survival and reduces distant recurrence for resected EGFR-mutated NSCLC; however, these benefits should be weighed against a higher but manageable risk of toxicity. Trial registration. PROSPERO ID: CRD420261381478