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.
Keywords: MAGNITUDE trial; Niraparib; abiraterone acetate; castration resistant; future trials; mechanism of action; prostate cancer; toxicity.
Metastatic prostate cancer, which is prostate cancer that has spread to other parts of the body, is still not curable, but researchers are working on better treatments. Some studies have tested combining two types of tablet medications: PARP inhibitors and androgen receptor blockers. Niraparib, a type of PARP inhibitor, has shown promise in helping patients with certain gene mutations in their cancer (like BRCA1/2) by slowing down cancer growth when used with other treatments like abiraterone acetate (which is an androgen receptor blocker). This combination of drugs has recently been approved in the US, Canada, and Europe for patients with these gene mutations. This review looks at how well niraparib works, especially when used with other treatments, for prostate cancer patients with these genetic changes in their cancer.