The role of targetable biomarker alterations in overall survival for non-small cell lung cancer (NSCLC) in a large integrated health system.

[BACKGROUND] Non-small cell lung cancer (NSCLC) comprises 85% of lung cancer cases and remains a leading cause of cancer-related mortality. Advances in next-generation sequencing (NGS) have enabled identification of actionable oncogenic alterations, though real-world data on the prognostic impact of these alterations in NSCLC are limited. This study aims to evaluate the association between specific oncogenic biomarker alterations and overall survival (OS) across all stages of NSCLC in a large, integrated health system, providing real-world evidence on the prognostic value of molecular profiling beyond treatment effects.

[METHODS] This retrospective cohort study included patients aged 18-89 years with primary NSCLC of all stages diagnosed between 2013 and 2020 from a large integrated healthcare system in the United States. Data from institutional cancer registry and electronic health records (EHRs) were analyzed to evaluate the association of , , , , , , , , and alteration status with OS at 1 and 3 years using Kaplan-Meier and Cox regression analyses.

[RESULTS] Among 9,834 patients, 38.8% underwent biomarker testing. and alterations were associated with improved OS at 1 and 3 years. alteration was linked to poorer 1-year OS only, while alteration was associated with worse 3-year OS only. Null associations were observed with , , , and alteration status after adjustment for demographic and clinical factors.

[CONCLUSIONS] Biomarker-defined subgroups in NSCLC demonstrate distinct survival patterns, emphasizing the prognostic significance of molecular profiling. and alterations confer favorable outcomes, while certain alterations such as and associate with poorer survival. These findings support the routine integration of biomarker testing into NSCLC management and highlight the need for biomarker-specific therapeutic approaches.