Abstract D088: Analysis of tumor mutational burden, cancer immunotherapy use and outcomes based on genomic ancestry in non-small cell lung cancer patients treated in community practice in the United States
Authors: Richie Nicole , Luhn Patricia , Ogbu Uzor , Wilson Gerren , Capra William , Lee Mark , Brawley Otis 
Published: September 2020

Abstract
Introduction Racial disparities in cancer care and outcome are multifactorial and well documented, being attributed to social determinants, access to and quality of care. In addition, variation in biologic drivers by self-reported race/ethnicity or genetic ancestry may contribute to inequities in outcomes. Differences in tumor mutational burden (TMB), an important predictor of response to cancer immunotherapy (CIT), have been reported in non-small cell lung cancer (NSCLC) patients of different genomic ancestries. The impact of differing TMB-levels on outcomes and underlying cause is unknown, though smoking is associated with increased TMB. This study seeks to describe the receipt of CIT-containing regimens and the distribution and relationship of TMB with overall survival in NSCLC patients across ancestral groups. Methods 3962 patients with advanced NSCLC diagnosed between 1/1/11 and 4/30/19 were selected from the de-identified Flatiron Health-Foundation Medicine (FMI) linked clinicogenomics database. TMB was categorized as high or low (16mutations (mut)/megabase (Mb) cut off). Genomic ancestry was classified as previously described by FMI. CIT use and TMB status was described by ancestry and the association of TMB status with overall survival (OS) from diagnosis was estimated using Cox proportional hazards models. Analyses were further stratified by genomic ancestry (European vs. Non-European) and receipt of CIT at any point after advanced diagnosis date. Results The study population was 72% European ancestry (EUR), 8% African (AFR), 5% American (AMR), and 3% Asian (ASN). Genomic ancestry was largely correlated with self-reported race. The use of CIT-containing regimens was similar across ancestries, from 36% - 45% for those of ASN and AFR ancestry, respectively. TMB levels varied across ancestry groups; patients of AFR ancestry had the highest median TMB level (9.6 mut/Mb, [Interquartile Range: 4.4 – 15.7]), whereas ASN had lowest (3.5 mut/Mb, [2.6, 13.0]). Median TMB for EUR patients was 7.8 mut/Mb [3.5 – 13.9]. Similar trends were observed among patients with a history of smoking, though overall TMB levels were higher. TMB-high patients accounted for 24% of those of AFR, 20% for EUR, and 27% and 5% for AMR and ASN ancestry respectively. TMB-high was associated with better survival in patients who had ever received CIT (0.63, [95% CI: 0.52, 0.77]). These results were consistent when stratified by EUR (0.62 [0.50, 0.77]) and non-EUR ancestry (0.59 [0.34, 1.02]). Conclusions We observed different levels of TMB across ancestral groups. Differences in prevalence of smoking may be a contributing factor. TMB-high was equally predictive of improved OS among patients receiving CIT for those of EUR and non-EUR ancestry. There were no observed differences in receipt of CIT based on genomic ancestry in this population. These results suggest that addressing reported inequitable access to TMB testing among African American NSCLC patients may improve racial/ethnic disparities in NSCLC outcomes.
Citation Format: Nicole Richie, Patricia Luhn, Uzor Ogbu, Gerren Wilson, William Capra, Mark Lee, Otis Brawley. Analysis of tumor mutational burden, cancer immunotherapy use and outcomes based on genomic ancestry in non-small cell lung cancer patients treated in community practice in the United States [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D088.