Combination niraparib and abiraterone for HRR-altered metastatic castration-resistant prostate cancer.

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.