ASPO Abstracts
Variation in KRAS/NRAS/BRAF Mutation Status by Age, Sex and Race/Ethnicity Among Patients with Metastatic Colorectal Cancer (mCRC)
Category: Molecular Epidemiology & Environment
Conference Year: 2022
Abstract Body:
Purpose of the Study: National guidelines recommend molecular profiling of KRAS, NRAS, and BRAF mutations in metastatic colorectal cancer (mCRC) to help inform targeted treatment or eligibility for clinical trials. The objective of this study was to investigate the association between patient demographic characteristics and tumor mutation status among patients with de novo mCRC. Methods: This study was conducted using the nationwide Flatiron Health electronic health record derived de-identified database including 10,365 patients diagnosed with de novo mCRC, between 2013-2020, with results for at least one biomarker tested at any time (KRAS, NRAS, or BRAF). Mutation status was defined as ever positive (mutant) and wild-type (WT). We used multivariable logistic regression models to investigate patient demographics associated with mutation status, separately for each biomarker, adjusted for microsatellite instability (MSI) and tumor site. Results: Overall, 47.2% of mCRC tumors were documented KRAS mutant (4,831 of the 10,245 tested for KRAS), 11% were BRAF mutant (759 of the 6,884 tested for BRAF), and 5.3% NRAS mutant (346 of the 6,584 tested for NRAS). Tumors with multiple mutations in these biomarkers were rare (n=136/7,474); 0.8%). We observed marked differences in tumor mutation status by age, between men and women, and across racial/ethnic groups. After adjusting for other demographic and clinical factors, older age was associated with an increased odds of having a KRAS or BRAF mutant tumor. Similarly, compared to men, women had higher odds of presenting with a KRAS (adjusted odds ratio (AOR): 1.30, 95% Confidence Interval (CI): 1.20-1.41) or BRAF (AOR: 1.87, 95% CI: 1.58-2.21) mutant tumor. Compared with white patients, Black patients had higher odds of having a KRAS mutant tumor (AOR: 1.60, 95% CI: 1.40-1.83). In contrast, Black (AOR: 0.54, 95% CI: 0.37-0.76) and Hispanic (AOR: 0.53, 95% CI: 0.32-0.84) patients had lower odds of presenting with a BRAF mutant tumor, compared to White patients. Age, sex, and race/ethnicity was not associated with NRAS mutation status. Conclusions: In this analysis of real-world data among patients with mCRC, KRAS and BRAF mutation status differs across age, sex and racial/ethnic groups. Understanding the distribution
Keywords: mCRC, biomarkers