Comparison of circulating tumor DNA between African American and Caucasian patients with metastatic castrate‐resistant prostate cancer post‐abiraterone and/or enzalutamide

Abstract

Background: African American men are much more likely than Caucasian men to be diagnosed with and to die of prostate cancer. Genetic differences likely play a role.The cBioPortal database reveals that African American men with prostate cancer have higher rates of CDK12 somatic mutations compared to Caucasian men. However, this does not account for prior prostate cancer treatments, which are particularly important in the castrate-resistant setting. We aimed to compare somatic mutations based on circulating tumor DNA (ctDNA) in metastatic castrationresistant prostate cancer (mCRPC) between African American and Caucasian men after exposure to abiraterone and/or enzalutamide.Methods: This single-institution retrospective study characterizes the somatic mutations detected on ctDNA for African American and Caucasian men with mCRPC who had progressed after abiraterone and/or enzalutamide from 2015 through 2022. We evaluated the gene mutations and types of mutations in this mCRPC cohort.Results: There were 50 African American and 200 Caucasian men with CRPC with available ctDNA data. African American men were younger at the time of diagnosis (p = 0.008) and development of castration resistance (p = 0.006). African American men were more likely than Caucasian men to have pathogenic/likely pathogenic (P/ LP) mutations in CDK12 (12% vs. 1.5%; p = 0.003) and copy number amplifications

Evaluation of Survival Outcomes Among Black and White Patients with Metastatic Castration-resistant Prostate Cancer: A Systematic Review and Meta-analysis

“…Previous studies did not reach an agreement on racial differences in the efficacy of androgen receptor–targeted therapies (ARTs) for mCRPC. Retrospective studies suggested superior overall survival (OS) outcomes for Black patients who received first-line abiraterone (ABI) [16] , [17] , but prospective trials revealed no significant race-based difference in ABI effectiveness [18] , [19] . A real-world analysis including nearly 4000 patients with mCRPC showed that ABI was correlated with superior OS for African American men in comparison to non-Hispanic White men, but there was no racial difference among patients receiving first-line enzalutamide (ENZ), indicating a significant race-treatment interaction association [17] .…”

Pathogenic/Likely Pathogenic Somatic CDK12 Mutations in Black Men With Prostate Cancer

“…We have noted distinct and statistically significant differences in P/LP somatic CDK12 mutation rates between Black and White men with prostate cancer in our nearly simultaneously published studies (published April 27, 2023). 2 Our peer-reviewed manuscript using ctDNA analysis in metastatic castrate-resistant prostate cancer (mCRPC) indicated a clear increased risk of P/LP CDK12 mutations (12% versus 1.5%; P = .003) in Black versus White patients. We also analyzed publicly available cBioportal data in that manuscript using tissue-based specimens and found that Black men with prostate cancer (not just patients with mCRPC) had approximately double the rate of P/LP CDK12 mutations (9.7% versus 5.1%, P = .0007).…”

“…We also analyzed publicly available cBioportal data in that manuscript using tissue-based specimens and found that Black men with prostate cancer (not just patients with mCRPC) had approximately double the rate of P/LP CDK12 mutations (9.7% versus 5.1%, P = .0007). 2 Further, we assessed the Tempus tissue-derived database and found that 7.2% of Black men versus 3.8% of White men had prostate cancer with detectable P/LP CDK12 mutations ( P < .001). 3 Very recently, Sivakumar et al have also published a tissue-based analysis and concluded that 10.0% of patients with prostate cancer with an African Ancestry had a P/LP CDK12 mutation as compared with 5.2% of men with European Ancestry ( P < .0001).…”