A graphical network structure shows the network of trials for different primary and secondary outcomes ( Figure 2 )

A graphical network structure shows the network of trials for different primary and secondary outcomes ( Figure 2 ). olaparib (HR = 0.27 with 95% CrI: 0.20C0.35), and niraparib (HR = 0.26 with 95% CrI: 0.17C0.41) were all highly effective in comparison with placebo at improving PFS. For HRD patients, both rucaparib (HR = 0.32 with 95% CrI: 0.24C0.42) and niraparib (HR = 0.38 with 95% CrI: 0.24C0.60) were all highly effective in comparison with placebo at improving PFS. For the overall population, olaparib-throughout (HR = 0.51 with D-Luciferin potassium salt 95% CrI: 0.34C0.76), rucaparib (HR = 0.37 with 95% CrI: 0.30C0.45), olaparib (HR = 0.35 with 95% CrI: 0.25C0.49), and niraparib (HR = 0.38 with 95% CrI: 0.30C0.48) were all highly effective in comparison with placebo at improving PFS. Regarding grade 3 or 4 4 adverse events, the incidence D-Luciferin potassium salt of grade 3 or 4 4 toxicity reactions to rucaparib and niraparib were significantly higher than in the olaparib group. In terms of discontinuations due to adverse events, the treatment discontinuations were not significantly different between the three drugs. In summary, all the included maintenance treatment regimens are effective regardless of BRCA mutational status, and no statistically significant differences between rucaparib, niraparib and Olaparib in Acvrl1 terms of PFS. In terms of safety profile, the three drugs present manageable adverse events. Clinicians should consider potential adverse events related to each of these interventions in clinical practice, and the adverse events are generally manageable. strong class=”kwd-title” Keywords: PARP inhibitor, platinum, ovarian cancer, network meta-analysis, progress-free survival Introduction Ovarian cancer is the eleventh most common cancer worldwide and the fifth leading cause of cancer-related death (1). Although most patients with advanced ovarian cancer respond to initial platinum-based chemotherapy following cytoreductive surgery, approximately 70% will experience relapse and require subsequent therapies. ROC cannot be cured, with most patients receiving multiple treatment lines before ultimately dying from the disease (2). D-Luciferin potassium salt Given the deeply researching of molecular pathways found to be dysregulated during the multistep process of oncogenesis, many therapeutic targets have been identified and gave significant results in the clinical practice, which driven the management of cancer into individualized treatments. Poly(ADP-ribose) polymerase inhibitors are one of new personalized treatments for patients with high-grade serous ovarian cancer and demonstrate a high survival advantage in several randomized controlled trials (RCTs) and meta-analyses (3C6). The treatment modality is based on the mechanisms of synthetic lethal and PARP trapping, especially for patients with homologous recombination deficiencies (HRD) (7). PARP inhibitors currently used for maintenance treatment for platinum sensitive ROC include olaparib, rucaparib, and niraparib. The D-Luciferin potassium salt three drugs had been approved from December 2014 to July 2017 for D-Luciferin potassium salt the treatment of ROC (5) and recommended as maintenance therapy for platinum sensitive ROC by the NCCN guideline (8). However, all PARP inhibitors have never been compared with each other because of the lack of head-to-head trials. Although recent traditional meta-analyses have been published on PARP inhibitors as maintenance treatment in platinum sensitive ROC (3C6), comparisons among the three drugs were little explored because of the limitation of traditional meta-analysis methods which is based on direct evidence (9). Thus, the comparative efficacy and safety of FDA-approved PARP inhibitors as maintenance treatment in platinum sensitive ROC is still unknown. To provide concrete evidence for clinical practice, there is an urgent need for a thorough comparison of survival and safety profile. Herein, we performed a network meta\analysis to compare the effectiveness and safety of FDA-approved PARP inhibitors (olaparib, rucaparib, and niraparib) as maintenance therapy in platinum sensitive ROC. Materials and Methods This study followed Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for Network Meta-Analysis (10). Literature Search A literature search was conducted on PubMed, Embase and the Cochrane Central Register in May 2020. The reference lists of studies identified through the initial screening were used to identify trials missed by the computerized database search. The following search terms were used: olaparib, niraparib, and rucaparib, PARP inhibitors, maintenance therapy, recurrent, and ovarian cancer. Eligibility and Exclusion Criteria The inclusion criteria were as follows. Participants: Patients with platinum sensitive ROC. Intervention: A history of FDA-approved PARP inhibitor (such as olaparib, niraparib, and rucaparib) as maintenance therapy for ROC. Comparators: placebo or another PARP inhibitor. Outcome: The primary outcome was progression free.

Comments are closed.