scholarly journals The efficacy and safety of the addition of poly ADP-ribose polymerase (PARP) inhibitors to therapy for ovarian cancer: a systematic review and meta-analysis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yingzhu Yang ◽  
Nannan Du ◽  
Laidi Xie ◽  
Jing Jiang ◽  
Jiahang Mo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Meta Analysis ◽  
Parp Inhibitors ◽  
Efficacy And Safety

scholarly journals Efficacy and Safety of PARP Inhibitor Combination Therapy in Recurrent Ovarian Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Ren ◽  
Leyin Zhang ◽  
Jieru Yu ◽  
Siqi Guan ◽  
Xinyang Dai ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Combination Therapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Parp Inhibitor ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
High Grade ◽  
Efficacy And Safety

ObjectivesThough it is known to all that PARP inhibitors (PARPis) are effective when used as maintenance alone for women with recurrent ovarian cancer (ROC), little is known about whether using them in combination with other drugs would contribute to a better efficacy. We performed a systematic review and meta-analysis to explore the efficacy and safety of PARPi combination therapy compared with monotherapy.Materials and MethodsWe searched for randomized controlled trials (RCTs) that offered the date we needed in PubMed, Embase, Cochrane, and major conference. Data extraction and processing were completed by three investigators to compare OS, PFS, and ORR both in intervention and in control subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. And we evaluated the within-study heterogeneity by using subgroup and sensitivity analysis.Results and ConclusionA total of three eligible RCTs covering 343 women were included. In PFS analysis, PARP inhibitor (PARPi) combination therapy can significantly improve PFS for women with ROC when compared with the controls (HR: 0.46, 95% CI: 0.35 to 0.59), especially for those with mutated BRCA (HR: 0.29, 95% CI: 0.19 to 0.45). And in OS analysis, combination therapy is not inferior to monotherapy (HR: 0.90, 95% CI: 0.50 to 1.61). As for ORR, the effectiveness of combination therapy and monotherapy was almost the same (RR: 1.04, 95% CI: 0.82 to 1.31). Additionally, combination therapy seldom causes more adverse events, both in all-grade and in high grade.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, International Prospective Register of Systematic Reviews (PROSPERO) (identifier, CRD42018109933).

scholarly journals Efficacy and safety of PARP inhibitors as the maintenance therapy in ovarian cancer: a meta-analysis of nine randomized controlled trials

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Fengping Shao ◽  
Jun Liu ◽  
Yaoyun Duan ◽  
Li Li ◽  
Liqun Liu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Parp Inhibitors ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Grade 3

Abstract Purpose: Poly ADP ribose polymerase (PARP) inhibitors can effectively kill cancer cells by restraining the activity of DNA repair enzymes and utilizing the characteristics of BRCA mutations. This article evaluates the efficacy and safety of PARP inhibitors (PARPis) in the maintenance treatment of ovarian cancer. Method: We searched for clinical trials in electronic databases. PARPis efficacy were evaluated by the hazard ratios (HR) and its 95% confidence intervals (95% CI) of overall survival (OS) and progression-free survival (PFS) between the PARPis groups and placebo groups, while the PARPis’ safety was assessed by relative risk (RR) values of adverse events (AEs) between the two arms. Results: The immature OS data manifested that patients with BRCA mutation receiving PARPis therapy versus placebo therapy appeared to have longer OS (HR = 0.78, 95%CI = 0.61–1.01; P = 0.06). Compared with placebo group, PARP group had a significant advantage in PFS in ovarian cancer patients with BRCA wild-type (BRCAwt), BRCA mutation (BRCAm), BRCA status unclassified, BRCA1 mutation subgroup and the BRCA2 mutation subgroup (BRCAwt: HR = 0.53, 95%CI = 0.42–0.68, P < 0.00001; BRCAm: HR = 0.30, 95%CI = 0.26–0.34, P < 0.00001; BRCA status unclassified: HR = 0.52, 95%CI = 0.41–0.66, P < 0.00001; BRCA1m: HR = 0.38, 95%CI = 0.29–0.48, P < 0.00001; BRCA2m: HR = 0.23, 95%CI = 0.10–0.57, P = 0.001). Our analysis revealed the incidence rates for AEs of grade ≥3 (grades 3 to 4) and serious AEs in PARPis group were 55.19% and 26.29%, respectively. Conclusion: Our meta-analysis demonstrates that PARPis therapy can significantly improve PFS in ovarian cancer patients, but it has no benefit in OS. However, the therapy is associated with a significant increase in the risk of AEs of grade ≥ 3 and serious AEs.

scholarly journals Efficacy and Safety of PARP Inhibitors in Advanced or Metastatic Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Xu Liu ◽  
Kan Wu ◽  
Dan Zheng ◽  
Chuanxu Luo ◽  
Yu Fan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Triple Negative ◽  
Meta Analysis ◽  
Objective Response ◽  
Parp Inhibitors ◽  
Hematological Toxicity ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
Significant Difference

PurposePoly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in metastatic triple-negative breast cancers (TNBCs). We therefore performed a systematic review and meta-analysis to evaluate the efficacy and safety of this drug in patients with advanced or metastatic TNBC.MethodsA systematic literature search of PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for synonyms of “PARP inhibitors” and “breast cancer” was carried out. All published phase II/III clinical studies of PARP inhibitors in patients with advanced/metastatic TNBC were screened. Data were extracted independently by two authors and analyzed using Review Manager software version 5.3. End points include overall response rate (ORR), progression-free survival (PFS), and adverse events.ResultsTen clinical trials were identified, with a total of 1,495 patients included. Pooled analyses showed that PARP inhibitors could provide a significant improvement of ORR [risk ratio (RR) = 2.00; 95% confidence interval (CI), 1.14–3.50; p = 0.02) and PFS [hazard ratio (HR) = 0.68; 95%Cl, 0.59–0.77; p < 0.0001) compared to chemotherapy in the whole population. In subgroup analysis, patients with BRCA mutation had a higher objective response to PARP inhibitor, with an RR of 2.85 (95%CI, 1.34–6.06; p = 0.007) compared to BRCA wild-type patients. However, no significant difference in ORR was observed between the homologous recombination deficiency (HRD) positive and non-HRD subgroups (RR = 1.82; 95%CI, 0.81–4.08; p = 0.14). Hematological toxicity is a common adverse event of PARP inhibitors.ConclusionsPARP inhibitors are effective options for the treatment of patients with advanced or metastatic TNBC. Compared with patients without germline BRCA mutation, patients with germline BRCA mutation could benefit more from PARP inhibitors. In clinical setting, hematological toxicity associated with PARP inhibitors should be monitored regularly.

scholarly journals The Era of PARP inhibitors in ovarian cancer: “Class Action” or not? A systematic review and meta-analysis

2018 ◽  
Vol 131 ◽  
pp. 83-89 ◽  
Author(s):  
Nicoletta Staropoli ◽  
Domenico Ciliberto ◽  
Teresa Del Giudice ◽  
Eleonora Iuliano ◽  
Maria Cucè ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ovarian Cancer ◽  
Meta Analysis ◽  
Parp Inhibitors ◽  
Class Action
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