Related Experiment Video
Updated: Jan 6, 2026
Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
Receipt of PARP Inhibitors in Patients With Metastatic Prostate Cancer Harboring BRCA1/2 Alterations
Micah Ostrowski1, Yeonjung Jo2, Chadi Hage Chehade1
1Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City.
Importance:
Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 alterations are eligible to receive poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as single agents or in combination with an androgen receptor pathway inhibitor after these agents showed survival improvement in their landmark clinical trials. However, data are limited regarding the uptake of PARP inhibitors in these patients.
Objective:
To investigate the use of PARP inhibitors in patients with mCRPC harboring BRCA1/2 alterations.
Design, Setting, And Participants:
This retrospective cohort study used the deidentified Flatiron-Health electronic health record-derived database of US community and academic practices to extract patient-level data. The data cutoff date was May 31, 2024. Patients with mCRPC with evidence of harboring BRCA1/2 alterations and alive after August 15, 2020 (ie, 3 months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.
Exposures:
Age, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.
Main Outcomes And Measures:
The receipt of PARP inhibitors. Multivariable logistic regression was conducted to assess the association between the exposures and the main outcome.
Results:
Of 24 105 patients with metastatic prostate cancer, 443 male patients (median [IQR] age, 72 [65-79] years) had mCRPC with BRCA1/2 alterations and were eligible and included in our analysis. Of these patients, 227 (51.2%) received a PARP inhibitor, whereas 216 (48.8%) did not. Compared with patients covered by a commercial health plan, those covered by Medicare were significantly more likely to receive a PARP inhibitor (odds ratio, 1.91; 95% CI, 1.02-3.66; P = .047). The odds of receiving a PARP inhibitor were not significantly higher in patients treated in community practice compared with those treated in academic centers (odds ratio, 1.64; 95% CI, 1.00-2.70; P = .05).
Conclusions And Relevance:
This retrospective cohort study of patients with mCRPC and evidence of BRCA1/2 alterations found that approximately half of patients did not receive PARP inhibitors despite evidence of survival improvement in this population. These findings highlight the need to increase awareness of the survival data and access to life-prolonging therapies in patients with mCRPC.
Insights
Approximately half of patients with metastatic castration-resistant prostate cancer (mCRPC) and BRCA1/2 alterations did not receive poly (ADP-ribose) polymerase (PARP) inhibitors. Increased awareness of survival data and access to these therapies is needed for eligible mCRPC patients.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 alterations are candidates for poly (ADP-ribose) polymerase (PARP) inhibitors.
- PARP inhibitors have demonstrated survival benefits in clinical trials for this patient population.
- Limited data exist on the actual uptake of PARP inhibitors in eligible mCRPC patients.
Purpose of the Study:
- To investigate the utilization patterns of PARP inhibitors in patients diagnosed with mCRPC and harboring BRCA1/2 alterations.
Main Methods:
- A retrospective cohort study was conducted using the Flatiron-Health electronic health record database.
- Included were mCRPC patients with BRCA1/2 alterations alive after August 15, 2020.
- Multivariable logistic regression analyzed associations between patient characteristics (age, race, insurance, practice type) and PARP inhibitor receipt.
Main Results:
- Out of 443 eligible mCRPC patients with BRCA1/2 alterations, 51.2% received a PARP inhibitor.
- Patients with Medicare insurance were more likely to receive a PARP inhibitor compared to those with commercial insurance (OR, 1.91; P=.047).
- No significant difference in PARP inhibitor uptake was observed between community and academic practice settings (OR, 1.64; P=.05).
Conclusions:
- Nearly half of mCRPC patients with BRCA1/2 alterations did not receive PARP inhibitors, despite proven survival benefits.
- Findings underscore the need for enhanced awareness regarding survival data and improved access to PARP inhibitors for this group.
- Strategies to increase the uptake of life-prolonging PARP inhibitors in mCRPC patients are warranted.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
02:34Inhibition of Cdk Activity
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...