Addition of Olaparib to the New Hormonal Agent Regimen for Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

Syah Mirsya Warli, Adrian Joshua Velaro, Naufal Nandita Firsty, Zaimah Zulkarnaini Tala


Background: The emergence of olaparib, a poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitor to treat metastatic castration-resistant prostate cancer (mCRPC), created a measurable clinical question on whether the agent positively influences the treatment outcomes and acceptable safety factors. The objective was to elaborate on the efficacy and safety of olaparib-added regimens in treating mCRPC patients as compared to the established guideline.

Methods: The literature search was performed on several scientific databases, e.g., PubMed, Cochrane, and ScienceDirect, by applying the Boolean Term method. Statistical and risk of bias (RoB) analyses were calculated through RevMan 5.4.1. to investigate our outcomes, i.e., progression-free survival (PFS) and overall survival (OS) with the reported adverse effects (AEs). These outcomes were presented in hazard ratio (HR) and risk ratio (RR).

Results: Three trials consisting of 1,325 individuals with comparable baseline characteristics were investigated. The meta-analysis showed that introducing olaparib into the regimens significantly improved the PFS (HR 0.59 (0.48 - 0.73); P < 0.05), which disclosed even better outcomes among mutated homologous recombinant repair (HRR) and ataxia-telangiectasia mutated (ATM) gene (HR 0.43 (0.30 - 0.62); P < 0.05) in 95% confidence interval (CI). Furthermore, similar outcomes were observed in OS analysis (HR 0.81 (0.67 - 0.99); P < 0.05), despite olaparib group disclosed higher AEs rate with insignificant difference in mortality rate.

Conclusion: The efficacy and safety of olaparib-added regimens in mCRPC patients need to be explored more extensively in trials because they are beneficial, particularly among HRR-mutated individuals.

World J Oncol. 2023;14(6):518-528


Castration-resistant prostate cancer; mCRPC; PARP; Olaparib; HRR mutation

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