2431 - Sociodemographic and Molecular Determinants of Disparities in NSCLC Outcomes: A Multi-Institutional Genomic Analysis
Presenter(s)
C. Marquez1, J. Y. Chang2, and D. C. Qian3; 1MD Anderson Cancer Center, Houston, TX, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3Department of Thoracic Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Metastatic non-small cell lung cancer (mNSCLC) remains a leading cause of cancer mortality, with outcomes shaped by age, sex, and race. While targeted therapies and immunotherapy have improved survival, treatment access and tumor molecular features vary across demographic groups. Age-related survival differences remain poorly understood, sex-based variations suggest distinct tumor biology, and racial/ethnic disparities may stem from both biological factors and healthcare access barriers. Tumor mutational burden (TMB) differs by race, though its impact on survival is unclear. This study aims to characterize molecular and sociodemographic differences in mNSCLC to identify disparities in actionable mutations, TMB, and OS, informing targeted interventions to improve equity in treatment and outcomes.
Materials/Methods: The molecular and clinical characteristics of mNSCLC were analyzed using the AACR Project GENIE database, incorporating patient data from 18 institutions across Europe and North America, as well as the MSK-MET cohort with detailed racial and ethnic classification. A total of 4,600 NSCLC cases were evaluated to characterize the genomic landscape, prevalence of targetable mutations, and molecular predictors of immunotherapy benefit.
Results: Patients diagnosed outside the 50–70 age range had significantly shorter OS compared to those diagnosed within this range (HR 1.21, 95% CI 1.03–1.43, P = 0.023 for patients <50; HR 1.22, 95% CI 1.11–1.33, P < 0.0001 for patients >70). Among younger patients, Hispanic individuals represented the highest proportion of mNSCLC diagnoses (18%) compared to 7% in non-Hispanic populations (P < 0.0001). Female patients exhibited significantly improved OS compared to males (median OS: 42 vs. 26 months; HR 0.69, 95% CI 0.63–0.75, P < 0.0001), which may be driven by a higher prevalence of EGFR mutations (30% in females). EGFR mutations were most common in Asian patients (56%), while KRAS mutations were rare in this group (11%). Black patients exhibited the highest TMB, with 9% having =20 mutations/Mb compared to 5% in non-Black patients (P = 0.019). However, despite higher TMB, Black patients experienced worse survival outcomes, suggesting barriers to immunotherapy access or unmeasured socioeconomic factors.
Conclusion: These findings highlight critical inequities in the genomic landscape and treatment outcomes of mNSCLC, emphasizing the need for targeted interventions. Strategies should include expanding NGS access across diverse populations, refining CT screening protocols to incorporate risk factors beyond smoking, and further investigating sex- and race-specific molecular drivers of disease. While this study provides valuable insights, limitations include the lack of data on smoking history, environmental exposures, and prior treatment regimens, emphasizing the need for improved data collection to develop more precise interventions aimed at reducing disparities in mNSCLC outcomes.