Targeted Therapy or Chemotherapy First? A Meta-Analysis in Resectable EGFR-Mutant Non-Small Cell Lung Cancer

Abstract Background: Resectable epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) remains at high risk of recurrence despite curative-intent surgery. EGFR tyrosine kinase inhibitors (EGFR-TKIs) and platinum-based chemotherapy are treatment options for resectable NSCLC. However, their comparative efficacy across adjuvant and neoadjuvant settings remains unclear. This meta-analysis compared the efficacy and safety of EGFR-TKIs versus chemotherapy. Methods: A systematic search of PubMed, ScienceDirect, Wiley, and Cochrane was performed up to May 2026. Eligible studies included randomized and comparative studies evaluating EGFR-TKIs versus chemotherapy in resectable EGFR-mutated NSCLC. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Secondary outcomes included grade 3/4 adverse events, relapse/recurrence, major pathologic response (MPR), pathologic complete response (pCR), R0 resection, and lymph node (LN) downstaging. Results: Ten studies involving 1,564 patients were included, with 742 patients in the targeted therapy group and 822 in the chemotherapy group. EGFR-TKIs significantly improved DFS compared with chemotherapy (HR 0.44; 95%CI 0.30–0.66; P<0.0001) post-operatively and reduced grade 3/4 adverse events (OR 0.23; 95%CI 0.06–0.80; P=0.02). In the neoadjuvant setting, EGFR-TKIs significantly increased major pathologic response (RR 13.42; 95%CI 4.27–42.19) and pathologic complete response (RR 6.11; 95%CI 1.66–22.46). No significant difference was observed in OS, relapse/recurrence, R0 resection, or LN downstaging. Conclusion: EGFR-TKIs provide better disease control, pathologic response, and safety than chemotherapy in resectable EGFR-mutated NSCLC. Current evidence supports adjuvant EGFR-TKI therapy as the more established strategy, while neoadjuvant use remains promising but requires further studies. Prospero: CRD420261436884