Frequencies of Common NSCLC KRAS and EGFR Variants in Black and White Americans

Lung cancer is the second leading cause of cancer and the leading cause of cancer-related deaths in the United States.¹ Cigarette smoking is the main cause of lung cancer,¹ and Black Americans report lower daily levels of cigarette smoking compared with White Americans yet are disproportionately affected by lung cancer, with higher prevalence and death rates.¹ Overall, 5-year survival rate is approximately 20%, but in patients with advanced non–small-cell lung cancer (NSCLC) with molecular profiles that can be targeted by treatment, overall survival has increased.¹ The research behind these advances has primarily been based on research conducted on White patients because only 83 samples from Black Americans are included in the Cancer Genome Atlas for lung cancer.¹ In addition, Black Americans have made up <4% of targeted therapy or immunotherapy clinical trial participants.¹

Pilling and colleagues undertook a retrospective study to compare treatment-relevant molecular data in Black and White Americans with NSCLC harboring either EGFR or KRAS mutations. The primary objective of the study was to determine the frequency of co-occurring alterations in the genes associated with NSCLC by cohort; secondary objectives included the use of targeted therapy and the timing of genetic testing in the cohorts. The study included data collected between 2010 and 2020 among patients with stage 3 or 4 NSCLC where KRAS or EGFR mutation was identified within 60 days of patient diagnosis.

The study included 642 patients with KRAS-mutated NSCLC and 348 patients with EGFR-mutated NSCLC. Mean time from diagnosis to first molecular test result was 20.9 days for Black Americans and 19.9 days for White Americans. In the Black American cohort, the EGFR G719S variant was more prevalent than in the White American cohort. No significant difference was seen in the other common EGFR or KRAS variants tested. KRAS mutation was associated with co-mutation in 100 patients. The most frequent co-mutations were TP53 (81.3% of Black patients and 65.0% of White patients), followed by KEAP1 (18.8% of Black patients and 8.3% of White patients), ATM (18.8% of Black patients and 9.5% of White patients), and PTEN (8.3% of White patients and no Black patients). The EGFR mutation was associated with TP53 co-mutation in 35 patients (4 Black and 31 White patients). Use of targeted EGFR therapy was reported in 52.9% of White and 47.9% of Black patients. Immune checkpoint inhibitor therapy was used in 39.3% of White and 29.2% of Black patients in the KRAS-mutation cohort. In this same cohort, 45.2% and 36.5% of White and Black patients, respectively, were given chemotherapy alone, and 21.9% and 13.5% of White and Black patients, respectively, were given combination therapy.

The investigators concluded that the higher rates of EGFR G719S variant occurs in Black patients, and this finding requires additional study to further evaluate the trends in co-mutations.

Reference

1. Mamdani H, Schwartz AG. Genomic Characterization of NSCLC in African Americans: A Step Toward "Race-Aware" Precision Medicine. J Thorac Oncol. 2020;15(12):1800-1802.

Source: Pilling A, Li P, Kane K, Wolf FM, Berry AB, Gadgeel SM. Race-specific genomic determinants of therapeutic response in African American NSCLC patients. J Clin Oncol. 2022;40(16):suppl,e21015-e21015.