The following is a summary of “Efficacy and safety of PARP inhibitors in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis of clinical trials,” published in the September 2023 issue of Oncology by Iannantuono et al.
PARP inhibitors are a standard treatment for advanced prostate cancer. Studies show that combining them with other drugs may be even more effective. Researchers performed a retrospective study and meta-analysis to assess the safety and efficacy of PARP inhibitors in patients with metastatic prostate cancer.
The study searched MEDLINE, EMBASE, CINAHL, and Web of Science databases, Cochrane CENTRAL for phase 2 or 3 clinical trials and evaluated efficacy outcomes, including progression-free survival (PFS), overall survival (OS), PSA decline >50% (PSA50), and objective response rate (ORR), as well as safety outcomes in the selected studies.
Seventeen clinical trials (PARPi monotherapy [n = 7], PARPi + androgen-receptor signaling inhibitors [ARSI] [n = 6], and PARPi + immune checkpoint inhibitors [ICI] [n = 4]) were included in the quantitative analyses. PARPi monotherapy improved radiographic PFS and OS over SoC in mCRPC patients with alterations in BRCA1 or BRCA2 genes but not in those with alterations in the ATM gene. Higher rates of PSA50 and ORR were reported in participants treated with PARPi + ARSI than in single-agent PARPi or PARPi + ICI. Although the rate of high-grade adverse events was similar across all groups, treatment discontinuation was higher in patients treated with PARPi-based combinations than PARPi monotherapy.
The study found that PARP inhibitors are ineffective for all mCRPC patients with DNA damage repair gene alterations. Choosing the right patients for this treatment is still difficult, but no new safety concerns were raised in this analysis.