Epidermal growth factor receptor (EGFR) mutations are major oncogenic drivers in non-small cell lung cancer (NSCLC), occurring in 30–50% of Asian patients. Neoadjuvant EGFR-tyrosine kinase inhibitors (EGFR-TKIs) may improve surgical outcomes in resectable EGFR-mutant NSCLC, but evidence from small, heterogeneous trials is inconsistent and the overall efficacy and safety remain unclear. To evaluate the efficacy and safety of neoadjuvant EGFR-TKI monotherapy in sensitizing EGFR-mutant NSCLC. PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to June 30, 2025. Prospective studies of neoadjuvant EGFR-TKI monotherapy in adults with genetically confirmed sensitizing EGFR-mutant NSCLC were eligible. Two investigators independently extracted data. Heterogeneity was assessed using Cochran’s Q test and the I2 statistic. Outcomes were pooled using random-effects (I2 > 50%) or fixed-effects (I2 ≤ 50%) meta-analyses. The primary outcomes were objective response rate (ORR) and incidence of grade ≥ 3 adverse events (AEs). Secondary outcomes included major pathological response (MPR) rate, pathologic complete response (pCR) rate, and complete (R0) resection rate. Predefined subgroup analyses were performed by age and ethnicity. Fifteen prospective studies involving 452 patients were included. The pooled ORR was 0.61 (95% confidence interval CI 0.54–0.67). The incidence of grade ≥ 3 AEs was 0.11 (95% CI 0.08–0.15), indicating an acceptable safety profile. The pooled MPR and pCR rates were 0.21 (95% CI 0.15–0.29) and 0.11 (95% CI 0.08–0.15), respectively. The pooled R0 resection rate was 0.90 (95% CI 0.86–0.94). ORR was higher in patients aged ≥ 60 years than < 60 years (0.69 vs 0.54, P = 0.01). pCR was higher in Chinese than non-Chinese patients (0.10 vs 0.03, P = 0.04). Neoadjuvant EGFR-TKI monotherapy was associated with promising efficacy and a manageable safety profile in stage I–III EGFR-mutant NSCLC patients. However, the evidence is derived predominantly from single-arm prospective studies, limiting inference regarding comparative efficacy and survival benefit. Large randomized controlled trials with long-term follow-up are needed to confirm these findings. PROSPERO CRD420251064957
Li et al. (Thu,) studied this question.