Biomarker-Directed Therapy in Black and White Men With Metastatic Castration-Resistant Prostate Cancer

• Type of Material: Article
• Authors: Clara Hwang, Henry Ford Health; Nicholas C. Henderson, University if Michigan; Shih-Chun Chu, University of Michigan; Brandon Holland, Wayne State University; Frank C. Cackowski, Wayne State University; Amanda Pilling, Henry Ford Health; Albert Jang, Tulane University; Shoshana Rothstein, Wayne State University; Matthew Labriola, Duke University; Joseph J. Park, University of Michigan; Alyssa Ghose, University of Michigan; Mehmet Asim Bilen, Emory University; Seema Mustafa, Emory University; Deepak Kilari, Medical College of Wisconsin, Milwaukee; Michael J. Pierro, Medical College of Wisconsin, Milwaukee; Bicky Thapa, Medical College of Wisconsin, Milwaukee; Abhishek Tripathi, University of Oklahoma; Rohan garje, University of Iowa; Aditya Ravindra, University of Iowa; Vadim S. Koshkin, University of California, San Francisco; Erik Hernandez, University of California, San Francisco; Michael T. Schweizer, University of Washington; Andrew J. Armstrong, Duke University; Rana R. Mckay, University of California, San Diego; Tanya B. Dorff, City of Hope; Ajjai S. Alva, University of Michigan; Pedro C. Barata, Tulane University
• Language: English
• Date: 2023-09-18
• Publisher: JAMA
• Publication Version: Final Published Version
• Copyright Statement: 2023 Hwang C et al. JAMA Network Open.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1001%2Fjamanetworkopen.2023.34208
• Title of Journal or Parent Work: JAMA Network Open
• Volume: 6
• Issue: 9
• Start Page: e2334208
• Keywords: Racial disparities; Prostate cancer; mCRPC
• Research Categories: Health Sciences, Oncology

Abstract

Importance Black men have higher incidence and mortality from prostate cancer. Whether precision oncology disparities affect Black men with metastatic castration-resistant prostate cancer (mCRPC) is unknown. Objective To compare precision medicine data and outcomes between Black and White men with mCRPC. Design, Setting, and Participants This retrospective cohort study used data collected by the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) consortium, a multi-institutional registry with linked clinicogenomic data, from April 2020 to December 2021. Participants included Black and White patients with mCRPC with molecular data. Data were analyzed from December 2021 to May 2023. Exposures Database-reported race and ethnicity. Main Outcomes and Measures The primary outcome was the frequency of actionable molecular data, defined as the presence of mismatch repair deficiency (MMRD) or high microsatellite instability (MSI-H), homologous recombination repair deficiency, or tumor mutational burden of 10 mutations per megabase or greater. Secondary outcomes included the frequency of other alterations, the type and timing of genomic testing performed, and use of targeted therapy. Efficacy outcomes were prostate-specific antigen response rate, site-reported radiographic response, and overall survival. Results A total of 962 eligible patients with mCRPC were identified, including 204 Black patients (21.2%; median [IQR] age at diagnosis, 61 [55-67] years; 131 patients [64.2%] with Gleason scores 8-10; 92 patients [45.1%] with de novo metastatic disease) and 758 White patients (78.8%; median [IQR] age, 63 [57-69] years; 445 patients [58.7%] with Gleason scores 8-10; 310 patients [40.9%] with de novo metastatic disease). Median (IQR) follow-up from mCRPC was 26.6 (14.2-44.7) months. Blood-based molecular testing was more common in Black men (111 men [48.7%]) than White men (317 men [36.4%]; P < .001). Rates of actionable alterations were similar between groups (65 Black men [32.8%]; 215 White men [29.1%]; P = .35), but MMRD or MSI-H was more common in Black men (18 men [9.1]) than White men (36 men [4.9%]; P = .04). PTEN alterations were less frequent in Black men than White men (31 men [15.7%] vs 194 men [26.3%]; P = .003), as were TMPRSS alterations (14 men [7.1%] vs 155 men [21.0%]; P < .001). No other differences were seen in the 15 most frequently altered genes, including TP53, AR, CDK12, RB1, and PIK3CA. Matched targeted therapy was given less frequently in Black men than White men (22 men [33.5%] vs 115 men [53.5%]; P = .008). There were no differences in response to targeted therapy or survival between the two cohorts. Conclusions and Relevance This cohort study of men with mCRPC found higher frequency of MMRD or MSI-H and lower frequency of PTEN and TMPRSS alterations in Black men compared with White men. Although Black men received targeted therapy less frequently than White men, no differences were observed in clinical outcomes.