Comparative efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) monotherapy versus combined EGFR-TKI and chemotherapy in resectable EGFR-mutant non-small cell lung cancer: a real-world multicenter retrospective study

Background: While perioperative immunotherapy and adjuvant targeted therapy have improved outcomes for advanced non-small cell lung cancer (NSCLC), evidence on preoperative targeted strategies remains limited. This study retrospectively evaluated the efficacy and safety of neoadjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy with or without chemotherapy in resectable EGFR-mutant NSCLC. Methods: Consecutive patients with EGFR-mutant NSCLC undergoing preoperative EGFR-TKI monotherapy or EGFR-TKI plus platinum-based chemotherapy followed by surgical resection were identified from three Chinese thoracic surgery prospectively maintained databases (2010–2023) from Peking University Cancer Hospital, Sun Yat-sen University Cancer Center, and The Affiliated Hospital of Putian University. Primary endpoints included major pathological response (MPR: ≤10% viable tumor) and pathological complete response (pCR). Safety, recurrence-free survival (RFS), and perioperative outcomes were secondary endpoints. Results: A total of 50 eligible patients were identified, including 29 females (58%) and 21 males (42%). The age range was 38 to 75 years, with an average age of 60 years. Among them, 22 patients (44%) were staged as cII, and 28 patients (56%) were staged as cIII. The EGFR mutations were found in 25 patients (50%) with exon 19 deletions, 21 patients (42%) with exon 21 L858R mutations, and 4 patients (8%) with other mutation types. Sixteen patients (32%) received first-generation TKIs, and 31 patients (62%) received third- generation TKIs. Chemotherapy mainly consisted of pemetrexed combined with carboplatin in 90% of cases. During neoadjuvant therapy, 6% of patients experienced grade 3 or higher adverse events (AEs), all in the combination therapy group. The overall objective response rate (ORR) was 64% (32/50), and 30 patients (60%) experienced a downstage in disease after treatment. The R0 resection rate was 96% (48/50), and 90% underwent video-assisted thoracoscopic surgery (VATS). Seven patients (14%) achieved pCR, and 18 patients (36%) achieved MPR postoperatively. Postoperative MPR and pCR rates were 36.0% (18/50) and 14.0% (7/50), respectively, with higher pCR in the combination group (20% vs. 5%; P=0.22). R0 resection was achieved in 96% (48/50). The overall 3-year RFS rates were 51.3% (53.4% combination vs. 46.7% monotherapy; P=0.42). Conclusions: Neoadjuvant EGFR-TKI therapy combined with chemotherapy demonstrated promising pathological responses and perioperative safety, supporting its feasibility in resectable EGFR-mutant NSCLC.