scholarly journals Comparison of the Efficacy and Safety of PARP Inhibitors as a Monotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Hongmei Wang ◽  
Meng Wu ◽  
Haonan Liu ◽  
Hang Zhou ◽  
Yang Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Recurrent Ovarian Cancer ◽  
Home Treatment ◽  
Efficacy And Safety ◽  
Risk Of Death ◽  
Platinum Sensitive ◽  
Grade 3

BackgroundThe present COVID-19 pandemic has tended toward normality. To provide convenient, safe, and effective home treatment programs for patients with recurrent ovarian cancer (ROC), the clinical efficacy and safety of poly (ADP-ribose) polymerase inhibitor (PARPi) (including olaparib, niraparib, and rucaparib) monotherapy as a maintenance treatment for platinum-sensitive ROC were systematically evaluated.MethodsNumerous electronic databases were systematically searched for randomized controlled trials (RCTs) of PARPi maintenance treatment for ROC that were published before June 2021. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was grade 3-4 adverse effects (AEs). After data extraction and the quality evaluation of the included studies, Bayesian network meta-analysis (NMA) was performed using R software. The ability of each treatment was ranked using the surface under the cumulative ranking (SUCRA) curve.ResultsThe analysis included five studies and 1390 patients. The NMA results demonstrated that compared with the placebo, olaparib and niraparib exhibited significant benefits in the gBRCA-mutated population, and respectively reduced the risk of death by 31% (HR = 0.69, 95% CI: 0.53-0.90) and 34% (HR = 0.66, 95% CI: 0.44-0.99). Olaparib, niraparib, and rucaparib were all found to be very effective in prolonging PFS in patients with ROC. All three PARPi treatments increased the number of grade 3-4 AEs in patients with ROC as compared with the placebo.ConclusionsOverall, olaparib and niraparib maintenance treatment can significantly prolong the OS of patients with gBRCA mutations. Furthermore, the three investigated PARPi monotherapy maintenance treatments can prolong PFS regardless of BRCA mutation status. Although the incidence of AEs in the treatment groups was found to be significantly higher than that in the placebo group, the patients in the treatment group tolerated the treatment. Home oral PARPi treatment can balance tumor treatment and pandemic prevention and control, and is the most convenient, safe, and effective home treatment method available against the background of the current COVID-19 pandemic. Systematic Review Registrationhttps://inplasy.com/inplasy-2021-6-0033/.

scholarly journals Comparative Efficacy and Safety of PARP Inhibitors as Maintenance Therapy in Platinum Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Yangchun Xu ◽  
Lei Ding ◽  
Yuan Tian ◽  
Miaomiao Bi ◽  
Ning Han ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Maintenance Treatment ◽  
Meta Analysis ◽  
Recurrent Ovarian Cancer ◽  
Efficacy And Safety ◽  
Comparative Efficacy ◽  
Platinum Sensitive ◽  
Highly Effective ◽  
Grade 3

This meta-analysis investigated the comparative efficacy and safety of PARP inhibitor monotherapy as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC). Electronic databases were systematically searched for relevant RCTs. The primary endpoint was PFS. The results were stratified based on three categories: BRCA mutated patients, HRD patients, and overall population. The secondary outcome were discontinuations due to adverse events and grade 3 or 4 adverse events in maintenance phase. Five eligible RCTs were included in the network meta-analysis. For patients with BRCA mutated ovarian cancer, olaparib-throughout (HR = 0.21 with 95% CrI: 0.081–0.55), rucaparib (HR = 0.23 with 95% CrI: 0.16–0.34), olaparib (HR = 0.27 with 95% CrI: 0.20–0.35), and niraparib (HR = 0.26 with 95% CrI: 0.17–0.41) were all highly effective in comparison with placebo at improving PFS. For HRD patients, both rucaparib (HR = 0.32 with 95% CrI: 0.24–0.42) and niraparib (HR = 0.38 with 95% CrI: 0.24–0.60) were all highly effective in comparison with placebo at improving PFS. For the overall population, olaparib-throughout (HR = 0.51 with 95% CrI: 0.34–0.76), rucaparib (HR = 0.37 with 95% CrI: 0.30–0.45), olaparib (HR = 0.35 with 95% CrI: 0.25–0.49), and niraparib (HR = 0.38 with 95% CrI: 0.30–0.48) were all highly effective in comparison with placebo at improving PFS. Regarding grade 3 or 4 adverse events, the incidence of grade 3 or 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 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.

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.

Secondary Cytoreductive Surgery in Platinum Sensitive Recurrent Ovarian Cancer: A Meta-Analysis

2021 ◽  
Author(s):  
Min-Hyun Baek ◽  
Eun Young Park ◽  
Hyeong In Ha ◽  
Sang-Yoon Park ◽  
Myong Cheol Lim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Meta Analysis ◽  
Recurrent Ovarian Cancer ◽  
Platinum Sensitive ◽  
Secondary Cytoreductive Surgery

Poly(ADP-ribose) polymerase inhibitors as maintenance treatment in patients with newly diagnosed advanced ovarian cancer: a meta-analysis

2020 ◽  
Vol 16 (10) ◽  
pp. 585-596 ◽  
Author(s):  
Ezzeldin M Ibrahim ◽  
Ahmed A Refae ◽  
Ali M Bayer ◽  
Emad R Sagr
Keyword(s):  
Ovarian Cancer ◽  
Randomized Clinical Trials ◽  
Brca Mutation ◽  
Meta Analysis ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Polymerase Inhibitors

Aim: Poly(ADP-ribose) polymerase inhibitors (PARPIs) improved progression-free survival among patients with recurrent ovarian cancer. This meta-analysis examined the effectiveness of PARPIs as maintenance strategy for newly diagnosed patients with advanced high-grade ovarian cancer with or without mutations. Materials & methods: Using defined selection criteria, a literature search identified four eligible randomized clinical trials involving 2386 patients. Results: Compared with placebo maintenance, PARPIs achieved a 46% reduction in the risk of progression or death as compared with placebo (hazard ratio: 0.54; 95% CI: 0.39–0.73; p < 0.0001). That benefit was shown in all clinical subgroups: among those with BRCA mutation, with negative/unknown BRCA mutation, and in those with homologous recombination deficient tumors. Data about the effect on overall survival are still premature. Conclusion: In patients with newly diagnosed advanced ovarian cancer, PARPIs maintenance after standard therapy achieved a significant improvement in progression-free survival as compared with placebo, overall and in all subgroups.

Recurrent ovarian cancer and management of  elderly patients: Results of a prospective trial of treosulfan focusing on patient's preference and clinical outcome (NOGGO-Preference-Study).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15520-e15520
Author(s):  
Radoslav Chekerov ◽  
Ioana Braicu ◽  
Philipp Harter ◽  
Stefan Fuxius ◽  
Sven Mahner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Elderly Patients ◽  
Prospective Trial ◽  
Individual Preference ◽  
Final Analysis ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Platinum Sensitive ◽  
Grade 3 ◽  
The Individual

e15520 Background: There is an increasing interest in the management of elderly patients in oncology. Treosulfan is effective as oral (p.o.) and intravenous (i.v.) formultion for recurrent ovarian carcinoma. Primary aim of this study was to explore the individual preference and compliance of elderly patients (≥ 65 years) for p.o. or i.v.-treosulfan. Secondary aims were to evaluate the ADL-score, toxicity, response and survival. We present the final analysis of patient’s characteristics and treatment choice, compliance of the treatment and toxicities for 123 included patients. Methods: Patients with platinum sensitive and resistant ovarian cancer had free choice of treosulfan i.v. (7000 mg/m² d1, q28d) or p.o. (600 mg/m² d1-28, q56d) for a maximum of 12 cycles (i.v.) or 12 months (p.o.). Indecisive patients were randomized. Toxicity was evaluated according to the NCI-CTC version 2.0. Results: 123 recruited patients received therapy and were able for analysis (median age 72 years, range 65-87). 102 patients chose i.v. and 17 p.o., 3 were randomized to i.v and 1 to p.o. Median ECOG was 1 (n=0-2), and median number of prior chemotherapy-regimens was 3 (n=1-6). Most common hematological toxicities (grade 3/4) were thrombopenia (18.7%), leukopenia (15.4%) and anemia (3.6%). Most frequent non-hematological toxicities (grade 3/4) were abdominal pain (7.3%), fatigue (5.7%) and constipation (4.9%). The median progressive-free survival was 116 days, and the median overall-survival was 239 days. There was no difference in survival and activities of daily life (ADL) score between i.v. and p.o. treosulfan. Conclusions: Although heavily pre-treated most elderly patients with recurrent ovarian cancer (85%) preferred the i.v.-treosulfan administration following their individual preference. Treosulfan therapy was generally well tolerated. There were no differences in the patient’s characteristics, survival and ADL-scores in both groups.

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