Efficacy of PARP Inhibitors as Maintenance Therapy for Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials

Introduction Prostate cancer is the second most common and fifth most aggressive cancer among men worldwide. (1) According to one estimate, 1 in 7 US men and 1 in 25 [...]
BACKGROUND: PARP inhibitors have been recently approved by the FDA for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Their effectiveness is seen when used with androgen deprivation therapy in patients with or without deleterious germline and somatic genetic mutations. OBJECTIVES: To identify all the randomized controlled trials (RCTs) in which PARP inhibitors have been assessed in the treatment of mCRPC, and to compare the efficacy of PARP inhibitors in these patients with standard-of-care (SOC)/antihormonal therapies like abiraterone acetate (Zytiga) or enzalutamide (Xtandi) in terms of progression-free survival (PFS) and overall survival (OS). SEARCH STRATEGY: A systemic review search was conducted using PubMed, Embase, and Central Cochrane Registry. SELECTION CRITERIA: Randomized clinical trials with PARP inhibitors, with or without antihormonal therapy, as the intervention arm, with SOC as control. DATA ANALYSIS: HRs were calculated for PFS and OS. For effect sizes, a confidence interval of 95% was used, and for statistical significance, a P value of less than .05 was used. Analysis was done using random and fixed effect analysis and both were reported. Heterogeneity was evaluated using I (2) statistic. RESULTS: Three RCTs were included in the analysis. PARP inhibitors showed a statistically significant improvement in OS when calculated using a fixed model (HR, 0.751; 95% CI, 0.582-0.968) but the improvement was not significant when calculated using a random model (HR, 0.758; 95% CI, 0.565-1.017; I (2) = 23). Similarly, the improvement in PFS was statistically significant when calculated using a fixed model (HR, 0.626; 95% CI, 0.521-0.752), and no statistical significance was noted with a random model (HR, 0.674; 95% CI, 0.437-1.039; I (2) = 80). CONCLUSIONS: PARP inhibitors contributed to significant increases in PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide. This efficacy was pronounced among the patients with deleterious germline or somatic homologous recombination repair gene mutations, although patients without these mutations also showed a better PFS and OS in comparison with SOC therapy. KEYWORDS: PARP inhibitors, metastatic castrationresistant prostate cancer (mCRPC), overall survival, progression-free survival