A Meta-Analysis of Randomized Clinical Trials Assessing the Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer

Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate cancer (CRPC). Poly-ADP ribose polymerase (PARP) inhibitors (PARPis) have been at the forefront of the treatment of CRPC. We aim to...

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Published inCurrent oncology (Toronto) Vol. 30; no. 10; pp. 9262 - 9275
Main Authors Alameddine, Zakaria, Niazi, Muhammad Rafay Khan, Rajavel, Anisha, Behgal, Jai, Keesari, Praneeth Reddy, Araji, Ghada, Mustafa, Ahmad, Wei, Chapman, Jahangir, Abdullah, Terjanian, Terenig O
Format Journal Article
LanguageEnglish
Published MDPI AG 01.10.2023
MDPI
Subjects
Antimitotic agents
Antineoplastic agents
castrate-resistant prostate cancer
Gene mutations
homologous recombination repair genes
Medical research
Medicine, Experimental
Metastasis
overall survival
PARP inhibitors
Product development
progression-free survival
Prostate cancer
Rankings
Systematic Review
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Summary:Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate cancer (CRPC). Poly-ADP ribose polymerase (PARP) inhibitors (PARPis) have been at the forefront of the treatment of CRPC. We aim to better characterize the progression-free survival (PFS) and overall survival (OS) in metastatic CRPC patients treated with PARPis. A systemic review search was conducted using National Clinical Trial (NCT), PubMed, Embase, Scopus, and Central Cochrane Registry. The improvement in overall survival was statistically significant, favoring PARPis (hazard ratio (HR) 0.855; 95% confidence interval (CI) 0.752–0.974; p = 0.018). The improvement in progression-free survival was also statistically significant, with results favoring PARPis (HR 0.626; 95%CI 0.566–0.692; p = 0.000). In a subgroup analysis, similar results were observed where the efficacy of PARPis was evaluated in a subgroup of patients without homologous recombination repair (HRR) gene mutation, which showed improvement in PFS favoring PARPis (HR 0.747; 95%CI 0.0.637–0.877; p = 0.000). Our meta-analysis of seven RCTs showed that PARPis significantly increased PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide.
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These authors contributed equally to this work.
ISSN:1718-7729
1198-0052
1718-7729
DOI:10.3390/curroncol30100669