Safety Profile of Niraparib as Maintenance Therapy for Ovarian Cancer: A Systematic Review and Meta-Analysis

Abstract

Background: Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment. Objective: To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC. Methods: PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated. Results: A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, p < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, p = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, p < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, p = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, p < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, p < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, p < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, p = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, p = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, p < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, p < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, p = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials. Conclusion: Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.

SPOCK2 Promotes the Malignant Behavior of Ovarian Cancer via Regulation of the Wnt/β-Catenin Signaling Pathway

“…Targeted therapy causes specific death of cancer cells by binding targeted drugs to specific cancer sites without affecting surrounding normal tissue cells [18]. Currently, targeted therapeutic agents that have been used in ovarian cancer include olaparib and niraparib, VEGF inhibitors, and the antiangiogenesis inhibitor bevacizumab, but the above-targeted agents are less used in clinical practice because of their narrow indications, high prices, and certain adverse effects [19][20][21]. Exploring the molecular mechanisms associated with ovarian cancer progression is the basis for developing novel diagnostic and therapeutic approaches for ovarian cancer.…”

An Updated Comprehensive Pharmacovigilance Study of Drug‐Induced Thrombocytopenia Based on FDA Adverse Event Reporting System Data

“…54 A metaanalysis showed that grade 3 to 4 thrombocytopenia was significantly observed in patients treated with niraparib. 55 Clinical trials had shown that thrombocytopenia is one of the most common adverse reactions to niraparib, occurring in 38%-52% of cases, with severe thrombocytopenia occurring in 8% to 28% of cases. [56][57][58] A pharmacovigilance study of adverse reactions to niraparib using FAERS showed similar results to this study (ROR 11.02 and IC 3.35).…”

“…Niraparib, a highly selective, potent poly(ADP‐ribose) polymerase 1 (PARP1) and PARP2 inhibitor was approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who have demonstrated a complete or partial response to platinum‐based chemotherapy 54 . A meta‐analysis showed that grade 3 to 4 thrombocytopenia was significantly observed in patients treated with niraparib 55 . Clinical trials had shown that thrombocytopenia is one of the most common adverse reactions to niraparib, occurring in 38%‐52% of cases, with severe thrombocytopenia occurring in 8% to 28% of cases 56‐58 .…”

Efficacy of oral ferric citrate hydrate treatment for anemia caused by niraparib: a case report

“…Grade 3 or 4 anemia occurs in 25.3-28.7% of patients and is managed by dose reduction, interruption, discontinuation, or red blood cell (RBC) transfusion [9]. Anemia frequently occurs within 3 months after niraparib maintenance therapy [10]. Notably, whether iron, folic acid, or vitamin B12 supplementation ameliorates anemia caused by PARP inhibitors remains unclear.…”