Who Gets Left Out of Precision Oncology? Real-World Driver Mutation Expression Patterns and Therapeutic Eligibility in a Diverse Single-Center Early-Stage Lung Adenocarcinoma Cohort

Introduction: Precision oncology in non-small cell lung cancer (NSCLC) is driven by identification of actionable genomic alterations; however, trials establishing these paradigms often underrepresent racial/ethnic minorities and report mutations without comprehensive subtype characterization. We aim to define real-world biomarker patterns, including subtype distributions, across a diverse lung adenocarcinoma cohort. Methods: A retrospective analysis of patients undergoing surgical resection for lung adenocarcinoma (2021–2025) at a single urban academic center was performed. Patients with available next-generation sequencing (NGS) were included. EGFR mutations were categorized as typical versus atypical (PACC variants, exon 20 insertions, T790M, non-L858R exon 21 alterations), and KRAS mutations as G12C versus non-G12C. Results: Of 292 patients, 40.8% (n = 119) were non-Hispanic Black, 28.1% (n = 82) Hispanic, 16.1% (n = 47) non-Hispanic White, 6.2% (n = 18) Asian, and 8.9% (n = 26) other/unknown. Hispanic ethnicity was independently associated with EGFR positivity (aOR 3.88, 95% CI 1.34–11.20). Among EGFR-positive tumors, 26% were atypical, with numerically higher proportions in Black (37%) and Hispanic (27%) patients as compared with White (14%) and Asian (0%) patients. Among all KRAS mutations, 58% (n = 65) were non-G12C variants, which were not independently associated with any racial/ethnic subgroup. Conclusion: In a diverse cohort, atypical EGFR and non-G12C KRAS mutations, including subtypes with limited targeted treatment options, were common and, for EGFR, appeared numerically more common in Black and Hispanic patients. These findings highlight a potential structural gap in precision oncology, in which underrepresented populations may be disproportionately affected. Comprehensive NGS and inclusive trial design are important in ensuring equitable access to biomarker-driven therapies.