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Published on: March 6, 2018
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Comparison of Real-World Outcomes between Patients with BRCA1/2-Positive and Homologous Recombination Repair-Negative
Mehmet A Bilen1, Sabree Burbage2, Carmine Rossi3
1Emory University School of Medicine, Atlanta, GA, USA.
Advances in Therapy
|June 17, 2025
Summary
Patients with BRCA-positive metastatic castration-sensitive prostate cancer (mCSPC) experience worse outcomes, including faster progression and shorter survival, compared to those with HRR-negative mCSPC. This highlights the need for targeted therapies for BRCA-positive prostate cancer.
Area of Science:
- Oncology
- Genetics
- Prostate Cancer Research
Background:
- Metastatic castration-sensitive prostate cancer (mCSPC) is a significant clinical challenge.
- Genetic mutations, such as in BRCA1/2, influence prostate cancer progression and treatment response.
- Understanding outcomes based on genetic profiles is crucial for personalized medicine.
Purpose of the Study:
- To compare time-to-next-treatment (TTNT), time-to-castration resistance (TTCR), and overall survival in mCSPC patients with BRCA1/2-positive (BRCA+) versus homologous recombination repair-negative (HRR-) status.
- To evaluate real-world outcomes for mCSPC patients based on their tumor's genetic profile.
Main Methods:
- A real-world study utilizing the Flatiron Health-Foundation Medicine, Inc. Clinico-Genomic Database (2017-2022).
- Included patients with mCSPC who initiated treatment after 1/1/2018 and had genetic testing.
- Compared outcomes between BRCA+ (n=149) and HRR- (n=1066) cohorts using weighted Kaplan-Meier and Cox models.
Main Results:
- BRCA+ mCSPC patients showed significantly shorter median TTNT (10.9 vs. 18.7 months) and TTCR (12.9 vs. 16.9 months) compared to HRR- patients.
- A higher proportion of BRCA+ patients progressed to next treatment (69.7% vs. 56.8%) and castration resistance (72.2% vs. 61.4%) within 24 months.
- Overall survival showed a trend towards worse outcomes in the BRCA+ cohort (80.6% vs. 85.4% at 24 months).
Conclusions:
- Patients with BRCA-positive mCSPC demonstrate poorer clinical outcomes with current advanced therapies.
- These findings underscore the urgent need for the development and implementation of genetically targeted therapies for BRCA-mutated prostate cancer.
- Personalized treatment strategies based on genetic markers are essential for improving outcomes in mCSPC.
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