Does Neoadjuvant Targeted Therapy Provide An Opportunity For Resectable Egfr-Mutant Lung Cancer: A Real-World Retrospective Study

Background: Although neoadjuvant chemotherapy could improve survival outcome in resectable non-small cell lung cancer (NSCLC), the efficacy of neoadjuvant targeted therapy is still unclear.Methods: We retrospectively reviewed clinical records of stage I-IIIA lung adenocarcinoma patients treated with neoadjuvant targeted therapy or chemotherapy prior to surgery. The collected data were compared between the two groups. Tumor samples were collected and analyzed by sequencing to explore the epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms.Results: A total of 134 patients were enrolled; of these, 119 (88.8%) had clinical stage II-IIIA disease. Radiographic response rate was significantly higher with neoadjuvant targeted therapy than with chemotherapy among patients harboring EGFR mutation [objective response rate (ORR): 55.8% vs. 32.6%; P=0.030]. EGFR exon 19 deletion achieved better tumor response than those with exon 21 L858R mutation (ORR: 70.0% vs. 40.0%; P=0.057). Postoperative complications, operation time, drainage volume, and postoperative hospital length of stay were comparable between two groups. There was no difference on disease free survival (DFS) between patients receiving neoadjuvant targeted therapy and chemotherapy (P=0.871), but those who continued long-term adjuvant targeted therapy had significantly longer DFS than those only treated with adjuvant chemotherapy postoperatively (P=0.011). A series of potential molecular mechanisms of EGFR-TKI primary resistance were detected; these included BIM deletion polymorphisms, EGFR T790M mutation, and PTEN, TSC1, PIK3CA, or STAT3 mutations. Patients who presented stable disease (SD) response after TKI therapy had significantly lower EGFR mutation abundance than PR response (P=0.032).Conclusions: Neoadjuvant EGFR-TKI appears to be more effective than conventional chemotherapy for EGFR-mutant NSCLC patients. This study provides evidence that needs to be investigated further in randomized controlled trials (RCT).