Abstract 7105: Analyses of real-world clinico-genomic and demographic data highlight the multifactorial causes of poor colorectal cancer outcomes in patients of African ancestry

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Abstract Background: Colorectal cancer (CRC) patients of African ancestry (AFR) have been reported to have shorter overall survival (OS) than patients of non-African ancestry (non-AFR). We analyzed real-world clinico-genomic data from a single tertiary cancer center, including treatment and outcomes, to investigate this disparity. Methods: We analyzed data from 4, 310 CRC patients diagnosed after 2014 and treated at Memorial Sloan Kettering Cancer Center (MSKCC), including 270 AFR and 4, 040 non-AFR patients. Patients had their tumors sequenced with MSK-IMPACT, a targeted DNA sequencing assay that identifies genomic alterations in 341-505 genes. Genetic ancestry was inferred from sequencing data, and patients with >80% African ancestry were classified as AFR. ​​OncoKB was used to identify clinically actionable genomic alterations, as well as alterations associated with treatment resistance. Type of medical insurance and Yost index based on billing address were recovered from institutional databases. Covariates used in our analyses included primary tumor location, stage at diagnosis, time from diagnosis (Dx) to arrival at MSK and metastatic burden. OS was measured from the time of Dx. Results: AFR patients had shorter OS (median 39.1 vs. 60.2 months, p<0.001) and presented with more advanced disease: they were more often diagnosed with stage IV disease (51.5% vs 44.3%, p=0.034), tended to arrive later at MSKCC (21.5% vs. 10% arriving >1 year after Dx, p<0.001), more often received prior treatment (29.5% vs 22.1%, p=0.01), and had higher rates of right-sided colon tumors (37.9% vs 21.1%, p<0.001). AFR patients exhibited higher metastatic burden during their clinical history, including higher frequency of liver (70.3% vs 59.3%, p<0.001), lung (57.8% vs 48.6%, p=0.005) and CNS (14.9% vs 8.5%, p=0.001) metastases. They also had lower rates of MSI tumors (6.6% vs 11.1%, p=0.073), fewer FDA-approved targetable alterations (6.1% vs 11.5%, p=0.006 - driven by BRAF), and more alterations resistant to FDA-approved drugs (60.7% vs 45.5%, p<0.001 - driven by KRAS). Overall, Medicaid usage was independently associated with shorter OS (median 29.3 vs. 59.9 months, p<0.001) and later arrival at MSKCC (17.7% vs. 10.4% arriving >1 year after Dx, p=0.024). AFR patients had a higher rate of Medicaid users (7.9 vs. 2.6%, p<0.001), which can partially explain their shorter OS. However, even when Medicaid and non-Medicaid users were analyzed separately, AFR patients still had worse OS (median 26.1 vs. 34.5 months, p=0.069, and 43.7 vs. 60.4 months, p=0.002, respectively). Conclusions: AFR ancestry and Medicaid use were additive factors associated with poor prognosis. This disparity could be at least partially explained by a combination of clinico-genomic factors, including more advanced disease at diagnosis and delayed arrival at the treating tertiary care center. Citation Format: Sharafudeen D. Abubakar, Henry Walch, Christina I. Lee, Chin-Tung Chen, Kanika Arora, Farheen Shah, Tejiri Agbamu, Michele Waters, Christopher Fong, Justin Jee, Michael F. Berger, Karuna Ganesh, Debyani Chakravarty, Walid K. Chatila, Nikolaus Schultz, Rona Yaeger, Julio Garcia-Aguilar, Francisco Sanchez-Vega. Analyses of real-world clinico-genomic and demographic data highlight the multifactorial causes of poor colorectal cancer outcomes in patients of African ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7105.

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