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Updated: Jun 4, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Combination niraparib and abiraterone for HRR-altered metastatic castration-resistant prostate cancer
Hayley Nicole Roberts1, Corinne Maurice-Dror1,2, Kim Nguyen Chi1,2
1Department of Medical Oncology, BC Cancer Agency, Vancouver, Canada.
Abstract:
Metastatic prostate cancer remains incurable. Though significant progress has been made in the field, the search for agents that improve outcomes for patients is ongoing. Several clinical trials have explored the benefit of combining PARP inhibitors (PARPi) with androgen receptor pathway inhibitors (ARPIs) for metastatic castrate resistant prostate cancer (mCRPC), especially those cancers with alterations in homologous recombination repair (HRR) genes. Niraparib, a highly selective inhibitor of PARP1 and PARP2, has been shown to confer a radiographic progression-free survival benefit in the treatment of mCRPC with HRR-associated gene alterations, particularly BRCA1 and BRCA2 (BRCA1/2), when combined with abiraterone acetate plus prednisolone (AAP). This combination has recently been approved in the USA, Canada and Europe for patients with mCRPC and a BRCA1/2 gene mutation. This review summarizes the evidence with regards to the pharmacologic activity and clinical efficacy of niraparib with a specific focus on its efficacy in combination with AAP in mCRPC patients with HRR alterations.
Insights
Niraparib combined with abiraterone acetate plus prednisolone offers a new treatment for metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 gene mutations. This combination improves radiographic progression-free survival in mCRPC with HRR alterations.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) is an incurable disease.
- Homologous recombination repair (HRR) gene alterations are found in some mCRPC cases.
- Combining androgen receptor pathway inhibitors (ARPIs) with PARP inhibitors (PARPi) is being investigated for mCRPC.
Purpose of the Study:
- To review the pharmacologic activity and clinical efficacy of niraparib.
- To focus on the efficacy of niraparib in combination with abiraterone acetate plus prednisolone (AAP) for mCRPC patients.
- To highlight the benefits in mCRPC with HRR alterations.
Main Methods:
- Review of clinical trial data and pharmacologic evidence.
- Focus on niraparib's mechanism as a PARP1/PARP2 inhibitor.
- Analysis of combination therapy outcomes with AAP.
Main Results:
- Niraparib, as a PARPi, demonstrates radiographic progression-free survival benefit in mCRPC.
- The combination of niraparib with AAP shows efficacy in mCRPC patients with HRR-associated gene alterations.
- Significant benefit observed particularly in patients with BRCA1/2 mutations.
Conclusions:
- Niraparib plus AAP is an approved treatment for mCRPC with BRCA1/2 mutations in the USA, Canada, and Europe.
- This combination represents a significant advancement for a specific subset of mCRPC patients.
- Further research may explore broader applications of PARPi in prostate cancer.
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