Disparities in Tumor Mutational Burden, Immunotherapy Use, and Outcomes Based on Genomic Ancestry in Non-Small-Cell Lung Cancer

• Published in: JCO global oncology Vol. 7; no. 7; pp. 1537 - 1546
• Main Authors: Brawley, Otis W, Luhn, Patricia, Reese-White, Deonna, Ogbu, Uzor C, Madhavan, Sriraman, Wilson, Gerren, Cox, Meghan, Ewing, Altovise, Hammer, Christian, Richie, Nicole
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health 01.09.2021; American Society of Clinical Oncology
• Subjects: Biomarkers, Tumor - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - therapy; Humans; Immunotherapy - methods; Lung Neoplasms - genetics; Lung Neoplasms - therapy; ORIGINAL REPORTS; Retrospective Studies
• ISSN: 2687-8941; 2687-8941
• DOI: 10.1200/GO.21.00309

In patients with advanced non-small-cell lung cancer (aNSCLC), tumor mutational burden (TMB) may vary by genomic ancestry; however, its impact on treatment outcomes is unclear. This retrospective, observational study describes treatment patterns of patients with aNSCLC by genomic ancestry and electronic health record (EHR)-reported race and/or ethnicity and evaluates differences in TMB, cancer immunotherapy (CIT) access, and treatment outcomes across racial and ancestral groups. Patients diagnosed with aNSCLC after January 1, 2011, were selected from a real-world deidentified clinicogenomics database and EHR-derived database; continuously enrolled patients were evaluated. Race and/or ethnicity was recorded using variables from the EHR database; genomic ancestry was classified by single-nucleotide polymorphisms on a next-generation sequencing panel. A threshold of 16 mutations per megabase was used to categorize TMB status. Of 59,559 patients in the EHR-derived database and 7,548 patients in the clinicogenomics database, 35,016 (58.8%) and 4,392 (58.2%) were continuously enrolled, respectively. CIT use was similar across EHR-reported race groups, ranging from 34.4% to 37.3% for non-Hispanic Asian and non-Hispanic Black patients, respectively. TMB levels varied significantly across ancestry groups ( < .001); patients of African ancestry had the highest median TMB (8.75 mutations per megabase; interquartile range, 4.35-14.79). In patients who had received CIT, high TMB was associated with improved overall survival compared with low TMB (20.89 11.83 months; hazard ratio, 0.60; 95% CI, 0.51 to 0.70) across genomic ancestral groups. These results suggest that equitable access to next-generation sequencing may improve aNSCLC outcome disparities in racially and ancestrally diverse populations.