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

• Published in: JAMA network open 2023-09, Vol.6 (9), p.e2334208-e2334208
• Main Authors: Hwang, Clara, Henderson, Nicholas C., Chu, Shih-Chun, Holland, Brandon, Cackowski, Frank C., Pilling, Amanda, Jang, Albert, Rothstein, Shoshana, Labriola, Matthew, Park, Joseph J., Ghose, Alyssa, Bilen, Mehmet A., Mustafa, Seema, Kilari, Deepak, Pierro, Michael J., Thapa, Bicky, Tripathi, Abhishek, Garje, Rohan, Ravindra, Aditya, Koshkin, Vadim S., Hernandez, Erik, Schweizer, Michael T., Armstrong, Andrew J., McKay, Rana R., Dorff, Tanya B., Alva, Ajjai S., Barata, Pedro C.
• Format: Article
• Language: English
• Subjects: Black people; Cohort analysis; Metastasis; Oncology; Online Only; Original Investigation; Precision medicine; Prostate cancer; White people
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2023.34208

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).PTENalterations were less frequent in Black men than White men (31 men [15.7%] vs 194 men [26.3%];P = .003), as wereTMPRSSalterations (14 men [7.1%] vs 155 men [21.0%];P < .001). No other differences were seen in the 15 most frequently altered genes, includingTP53,AR,CDK12,RB1, andPIK3CA. Matched targeted therapy was given l