Dataset Information

Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

ABSTRACT:

Introduction

Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering BRCA genes status.

Methods

We searched PubMed, EMBASE, and MEDLINE for trials involving patients with PS rOC treated with BEV or PARPi. Different comparisons were performed for patients included in the PARPi trials, according to BRCA genes status as follows: all comers (AC) population, BRCA 1/2 mutated (BRCAm), and BRCA wild type patients (BRCAwt).

Results

In the overall population, PARPi prolonged PFS with respect to BEV (hazard ratio (HR) = 0.70, 95% CI 0.54-0.91). In the BRCA mutated carriers, the PFS improvement in favor of PARPi appeared to be higher (HR = 0.46, 95% CI 0.36-0.59) while in BRCAwt patients the superiority of PARPi over BEV failed to reach a statistically significance level (HR = 0.87, 95% CI 0.63-1.20); however, according to the SUCRA analysis, PARPi had the highest probability of being ranked as the most effective therapy (90% and 60%, for PARPi and BEV, respectively).

Conclusions

PARPi performed better as compared with BEV in terms of PFS for the treatment of PS rOC, especially in BRCAm patients who had not previously received PARPi.

SUBMITTER: Bartoletti M

PROVIDER: S-EPMC7312982 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

Bartoletti Michele M Pelizzari Giacomo G Gerratana Lorenzo L Bortot Lucia L Lombardi Davide D Nicoloso Milena M Scalone Simona S Giorda Giorgio G Baldassarre Gustavo G Sorio Roberto R Puglisi Fabio F

International journal of molecular sciences 20200527 11

<h4>Introduction</h4>Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of direct comparison, we performed a network meta-analysis considering <i>BRCA</i> genes status.<h4>Methods</h4>We searched PubMed, EMBASE, and MEDLINE for trials involving patien ...[more]

PMID: 32471250

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Project description: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.

Project description: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/.

Project description:Background: The Platinum-based combination has been proven to have an outstanding effect on patients with platinum-sensitive recurrent ovarian cancer (PSROC), but the best scientific combination has not been established yet. The present study is aimed to seek the best treatment plan for PSROC. Methods: We did a systematic review and Bayesian network meta-analysis, during which lite before March 2022 were retrieved on PubMed, Embase, Web of Science, and Cochrane Central Registry of Controlled databases. We included randomized controlled clinical trials comparing chemotherapy combinations with other treatments for patients with PSROC. The important outcomes concerned were progression-free survival (PFS) (the primary outcome), overall survival (OS), objective response rate (ORR), adverse events (AEs), and AEs-related discontinuation. All outcomes were ranked according to the surface under the cumulative ranking curve. Results: 26 trials involving 10441 patients were retrieved in this study. For the initial treatment of PSROC, carboplatin plus pegylated liposomal doxorubicin (PLD) plus bevacizumab had the best PFS [hazard ratio (HR) 0.59, 95% credible interval (CI) 0.51-0.68]; Carboplatin plus paclitaxel plus bevacizumab resulted in the best OS (HR 1.22, 95% CI 1.09-1.35) and ORR [odds ratio (OR) 1.22, 95% CI 1.09-1.35]. For the maintenance therapy in PSROC, poly (ADP-ribose) polymerase inhibitors (PARPi) following platinum-based chemotherapy provided the best PFS (HR 0.64, 95% CI 0.61-0.68), the highest frequency of adverse events of grade three or higher (OR 0.18, 95% CI 0.07-0.44) but the treatment discontinuation was generally low. Subgroup analysis suggested that trabectedin plus PLD was comparable to single platinum in prolonging PFS in the platinum-free interval (6-12 months). Conclusion: Both platinum-based chemotherapy plus PARPi and platinum-based chemotherapy plus bevacizumab had higher survival benefits than other treatments in PSROC. Trabectedin plus PLD might be a potential alternative treatment strategy for the partially platinum-sensitive subpopulation with intolerance to platinum. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?], identifier [CRD42022326573].

Dataset Information

Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

Introduction

Methods

Results

Conclusions

Publications

Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

Similar Datasets

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