Homologous Recombination Repair Testing Patterns and Outcomes in mCRPC by Alteration Status and Race
Bibliographic record
Abstract
Mehmet Asim Bilen,1 Ibrahim Khilfeh,2 Carmine Rossi,3 Erik Muser,2 Laura Morrison,3 Annalise Hilts,3 Lilian Diaz,3 Patrick Lefebvre,3 Dominic Pilon,3 Daniel J George4 1Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA; 2Janssen Scientific Affairs, LLC, Horsham, PA, USA; 3Analysis Group, Inc., Montréal, QC, Canada; 4Department of Medicine, Duke University Cancer Center, Durham, NC, USACorrespondence: Carmine Rossi, Analysis Group, Inc., 1190 avenue des Canadiens-de-Montréal, Tour Deloitte, Suite 1500, Montréal, QC, H3B 0G7, Canada, Tel +1 514-871-4233, Email carmine.rossi@analysisgroup.comBackground: Alterations in DNA damage repair genes in advanced prostate cancer (PC) may impact responses to therapy and clinical outcomes. This study described homologous recombination repair (HRR) testing patterns and clinical outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) by HRR alteration status and race in the United States (US).Methods: Clinical data in the nationwide (US-based) Flatiron Health-Foundation Medicine, Inc. (FMI) Metastatic PC Clinico-Genomic Database were evaluated (01/01/2011– 12/31/2022). Patients initiating first-line (1L) mCRPC therapy on or after mCRPC diagnosis were included. Testing patterns, time-to-next treatment, overall survival (OS), and time-to-prostate specific antigen response were described.Results: Of the 1367 patients with mCRPC and at least one HRR panel test prior to or on the date of 1L mCRPC therapy initiation, 332 (24.3%) were HRR positive (White patients: n = 219 [66.0%]; Black patients: n = 37 [11.1%]) and 1035 (75.7%) were HRR negative (White patients: n = 702 [67.8%]; Black patients: n = 84 [8.1%]). The mean time between first positive test and 1L mCRPC therapy initiation date was 588 days (White patients: 589 days; Black patients: 639 days). Among HRR positive relative to negative patients, trends for faster progression (respective 12-month rate overall: 71.1% and 63.7%; White patients: 72.5% and 64.0%; Black patients: 65.4% and 56.4%), shorter OS (respective 24-month rate overall: 46.8% and 51.9%; White patients: 48.6% and 46.2%; Black patients: 52.8% and 54.1%), and decreased treatment response (respective 12-month rate overall: 24.3% and 37.9%; White patients: 24.5% and 35.2%; Black patients: 17.0% and 43.9%) were observed.Conclusion: Patients with mCRPC positive for HRR alterations tended to exhibit poorer treatment responses and clinical outcomes than those with a negative status. These findings highlight the importance of timely genetic testing in mCRPC, particularly among Black patients, and the need for improved 1L targeted therapies to address the unmet need in HRR positive mCRPC.Keywords: burden of illness, electronic health records, homologous recombination repair genes, metastatic castration-resistant prostate cancer, next-generation sequencing testing, precision therapy
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".