ASCO GU 2023: Comparison of ctDNA Between African American and Caucasian Patients with CRPC Post Abiraterone And/or Enzalutamide

(UroToday.com) It is now widely appreciated that African American men experience higher incidence of and mortality from prostate cancer, yet the sources of these discrepancies are incompletely elucidated. Dr. Jang and co-authors hypothesized that there are genetic differences between African American and Caucasian patients with advanced prostate cancer, which may contribute to differences in outcomes and survival.

 In this abstract, the authors present ctDNA from patients in both groups following treatment of CRPC with abiraterone acetate and/or enzalutamide. Guardant360 was performed on consecutive African American and Caucasian patients with prior exposure to abiraterone and/or enzalutamide who were treated at Tulane Cancer Center between 2015-2022. Mutations and amplifications were included among a list of 73-80 genes on the targeted panel and matched to associated annotated clinical data. Inclusion of pathogenic mutations were limited to those mutations with variant allele fraction of >0.5%.

 Comparison between baseline demographics were largely similar, save for a younger age of diagnosis and age of transition to castration resistant prostate cancer (CRPC) in African American v Caucasian (57 v 62, p=0.008; 63 v 68, p=0.006). Prior treatments were similar between groups (Table 1).

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Most patients in each group had at least one somatic mutation detected (40 AA (80%) and 161 C (80.5%). The most commonly identified pathogenic (P) or likely pathogenic (LP) alterations in both groups were in genes TP53 (44% and 46%, respectively), AR (50% and 39%), and PIK3CA (14% and 9%). Among detected alterations, both CDK12 (12% v 1.5%, OR 8.955, p=0.003) and KIT (8.0% v 1.5%, OR 5.710, p=0.031) were more likely to be mutated in African American v Caucasian patients (Table 2).

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The authors also queried for difference in type of genomic alteration between each race group. Among copy number changes and mutation type (e.g., amplification, deletion, duplication, frameshift, and indels), frameshift mutations were more frequently identified in AA patients (14/50, 28% v 29/200, 14.5%, OR 2.293, p=0.035). Among the conclusions, the authors offer CDK12 and KIT as genes that, when mutated, may be associated with aggressive features and treatment resistance. Most intriguingly, the authors also speculate that the identification of increased frequency of frameshift mutations may be associated with more immunogenic tumors, which could have implications for treatment modalities.

Presented by: Albert Jang, MD, Tulane University School of Medicine, New Orleans, LA

Written by: Jones Nauseef, MD, PhD, Assistant Professor of Medicine within the Division of Hematology and Medical Oncology, Sandra and Edward Meyer Cancer Center, and Englander Institute for Precision Medicine Weill Cornell Medicine and Assistant Attending physician at NewYork-Presbyterian Hospital. @DrJonesNauseef on Twitter during the 2023 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 16 – Saturday Feb 18, 20223