Real-world outcomes in patients with biomarker-selected early-stage non-small cell lung cancer.

11156 Background: Extensive literature has assessed the prognostic value of Lung driver mutations (LDMs) in advanced non-small cell lung cancer (aNSCLC). However, their role in predicting outcomes in early-stage cases (eNSCLC) is less defined due to limited data on biomarker-selected eNSCLC. Study variations have led to diverse findings on the prognostic value of individual LDMs in eNSCLC. Methods: We retrospectively analyzed patients with resected stage I-IIIa NSCLC diagnosed between 2011-2023 using the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine lung clinico-genomic database, which consolidates data from approximately 280 US cancer clinics (~800 sites of care). We allocated patients to five cohorts classified by early-stage LDM status: ALK+, EGFR+, KRAS G12C+, KRAS non-G12C+ and wild-type (WT - negative for the listed biomarkers). The clinical attributes and treatment patterns for this cohort were described by our group in a previous abstract; here we analyze recurrence-free and overall survival (RFS and OS) by cohort, using the Kaplan-Meier method. We used Cox regression for multivariate analysis, controlling for demographic and clinical characteristics including age, race, insurance status, stage, histology, and smoking status. Results: The sample contained 1,595 stage I-IIIa patients with known LDM status. Of these, 2.8%, 20.4%, 10.7%, 19.3%, and 46.8% were ALK+, EGFR+, KRAS G12C+, KRAS non-G12C+, and WT. Median OS and RFS were shorter in the WT group compared to any LDM group; results can be found in the table. These differences in OS and RFS persisted in multivariate analysis; hazard ratios (HR) were all statistically significant (p<0.05) and can be found in the table below. Conclusions: In this real-world analysis, patients with eNSCLC LDM-positive tumors had improved OS and RFS relative to WT patients. Differences in OS between WT and LDM+ patients are likely due to frequent receipt of targeted therapy (TT) following progression to advanced disease. However, the small fraction of patients that received adjuvant TT within 6 months of surgery (described in our previous abstract) is not likely to explain observed differences in RFS; thus the differences may be due to innate characteristics of these LDMs. [Table: see text]