Efficacy of neoadjuvant immunochemotherapy in the treatment of stage III non-small-cell lung cancer with cancer driver gene mutations

Background: Patients with non-small-cell lung cancer (NSCLC) and cancer driver gene mutations are mainly treated with targeted therapy. Research into the application of neoadjuvant immunochemotherapy for these patients is active and ongoing. In this study, we assessed the feasibility and safety of immunochemotherapy as a neoadjuvant treatment in patients with stage III NSCLC with common cancer driver gene mutations. Methods: This retrospective study enrolled patients who had stage III NSCLC with the results of driver mutation testing [including epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), c-ros proto-oncogene 1, receptor tyrosine kinase (ROS1), rearranged during transfection (RET), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)] and received neoadjuvant immunochemotherapy. The patients were followed for at least 1 year after the operation or until the day the treatment was discontinued. The primary endpoints were objective response rate (ORR) and adverse events (AEs), while the secondary endpoints were pathological response among patients who undergo surgery, disease-free survival (DFS) and overall survival (OS). Results: From 2020 to 2022, a total of 34 patients with stage III NSCLC were included in this study and were categorized into two groups according to the presence of cancer driver gene mutations: a mutation group (n=22) and a wild-type (WT) group (n=12). The rate of ORR in the WT group was 58.3%, and the rate of ORR in the mutation group was 68.2%. And no postoperative deaths or grade 3 or 4 AEs were observed in either of the groups. Among the patients who underwent surgery, the major pathological response (MPR) rate in the WT group and the mutation group was 75.0% and 47.0%, respectively (P=0.23). The pathological complete response (pCR) rate in the WT group and in the mutation group was 37.5% and 23.5%, respectively (P=0.64). The 1-year DFS rate in the WT group and the mutation group was 87.5% and 82.4%, respectively, while the 1-year OS rates in the WT group and the mutation group were both 100.0%. Conclusions: The potential of neoadjuvant immunochemotherapy for patients with stage III NSCLC with cancer driver gene mutations is promising.