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Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative Metastatic Castration-Sensitive Prostate Cancer.

Advances in therapy 2025 Vol.42(8) p. 3945-3959

Bilen MA, Burbage S, Rossi C, Khilfeh I, Diaz L, Wang Y, Pilon D, Brown G, Shore N, Lowentritt B, Lin DW

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[INTRODUCTION] This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with BRCA1/2-positive (BRCA+) and homologous re

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  • p-value p = 0.009
  • p-value p = 0.001
  • HR 1.46

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BibTeX ↓ RIS ↓
APA Bilen MA, Burbage S, et al. (2025). Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative Metastatic Castration-Sensitive Prostate Cancer.. Advances in therapy, 42(8), 3945-3959. https://doi.org/10.1007/s12325-025-03270-z
MLA Bilen MA, et al.. "Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative Metastatic Castration-Sensitive Prostate Cancer.." Advances in therapy, vol. 42, no. 8, 2025, pp. 3945-3959.
PMID 40528125

Abstract

[INTRODUCTION] This real-world study compared time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival between patients with BRCA1/2-positive (BRCA+) and homologous recombination repair-negative (HRR-) metastatic castration-sensitive prostate cancer (mCSPC).

[METHODS] Patients who received a genetic test and initiated treatment for mCSPC (index date) after 1/1/2018 were selected from the Flatiron Health-Foundation Medicine, Inc. Metastatic PC Clinico-Genomic Database (1/1/2017-12/31/2022). Outcomes were compared between patients with ≥ 1 positive BRCA test (BRCA+) and those without detected HRR mutations (HRR-) using weighted Kaplan-Meier analyses and Cox proportional hazards models after baseline characteristics (12 months pre-index) were balanced using inverse-probability of treatment weighting.

[RESULTS] In total, 149 patients with BRCA+ and 1066 with HRR- mCSPC were included. Baseline characteristics were well-balanced after weighting. By 24 months after treatment initiation, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to next treatment [69.7% vs. 56.8%; hazard ratio (HR) = 1.45 (95% confidence interval (CI) 1.10, 1.92), p = 0.009]; median TTNT was shorter in the BRCA+ than the HRR- cohort (10.9 vs. 18.7 months). By 24 months, a significantly higher proportion of the BRCA+ than the HRR- cohort progressed to castration resistance [72.2% vs. 61.4%; HR = 1.46 (95% CI 1.16, 1.84), p = 0.001]; median TTCR was shorter in the BRCA+ than HRR- cohort (12.9 vs. 16.9 months). Numerically fewer patients in the BRCA+ than the HRR- cohort survived 24 months after PC diagnosis [80.6% vs. 85.4%; HR = 1.46 (95% CI 0.99, 2.14), p = 0.054].

[CONCLUSION] Findings demonstrate worse outcomes for patients with BRCA+ mCSPC treated with available advanced therapies, supporting the need for effective genetically targeted therapies in this population.

MeSH Terms

Humans; Male; Aged; Prostatic Neoplasms, Castration-Resistant; BRCA2 Protein; BRCA1 Protein; Middle Aged; Recombinational DNA Repair; Mutation; Time-to-Treatment; Neoplasm Metastasis; Aged, 80 and over; Retrospective Studies

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