Neoadjuvant Immunochemotherapy for Stage II-IIIB Non-Small Cell Lung Cancer With Mutations Beyond EGFR 19del, L858R, and ALK Rearrangement.

Abstract

Neoadjuvant immunochemotherapy (neoICT) is not currently recommended for patients with stage II-IIIB non-small cell lung cancer (NSCLC) harboring oncogenic driver mutations, especially tyrosine kinase inhibitor-sensitizing epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). This study aimed to compare the pathologic response and survival outcomes between neoICT and neoadjuvant chemotherapy (neoChT) in patients with stage II-IIIB NSCLC harboring driver mutations beyond EGFR exon 19 deletion (19del), exon 21 L858R, and ALK rearrangement. Patients with stage II-IIIB NSCLC harboring driver mutations (EGFR 20ins/EGFR G719X/KRAS/BRAF/c-MET/HER-2/ROS1/RET/PIK3CA) who underwent neoICT or neoChT followed by curative-intent resection were retrospectively enrolled between November 2019 and August 2023. Kaplan-Meier analysis was performed to evaluate recurrence-free survival (RFS). Multivariable Cox proportional hazards regression was used to identify factors influencing survival outcomes after propensity score matching (2:1). A total of 52 and 24 patients received neoICT and neoChT, respectively. Kirsten rat sarcoma virus (KRAS) mutations were detected in 67.1% (51 of 76) of patients. The major pathologic response (MPR) rates were 53.8% and 4.2%, respectively. NeoICT conferred better RFS than neoChT (2-year RFS rate: 79.5% vs 49.9%; log-rank P = .012). After matching, multivariable Cox proportional hazards regression demonstrated that neoICT was associated with improved RFS compared with neoChT (hazard ratio, 0.33; 95% CI, 0.14-0.80). Similar findings were observed in both the KRAS-mutant and non-KRAS-mutant subgroups. In the neoICT group, nonadenocarcinoma histologic features and elevated programmed cell death ligand 1 levels were correlated with higher MPR rates. NeoICT resulted in superior pathologic response and survival compared with neoChT in both KRAS-mutant and non-KRAS-mutant subgroups.