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.

Long-term follow-up confirms a survival advantage of the paclitaxel–cisplatin regimen over the cyclophosphamide–cisplatin combination in advanced ovarian cancer

2003 ◽  
Vol 13 (Suppl 2) ◽  
pp. 144-148 ◽  
Author(s):  
M. J. Piccart ◽  
K. Bertelsen ◽  
G. Stuart ◽  
J. Cassidy ◽  
C. Mangioni ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Randomized Clinical Trials ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Clinical Response Rate ◽  
Free Survival ◽  
Long Term Follow Up ◽  
Clinically Significant

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European–Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin–paclitaxel regimen over cisplatin–cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

Adverse events (AEs) with maintenance olaparib in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Phase III SOLO1 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5539-5539
Author(s):  
Nicoletta Colombo ◽  
Kathleen N. Moore ◽  
Giovanni Scambia ◽  
Ana Oaknin ◽  
Michael Friedlander ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Brca Mutation ◽  
Supportive Therapy ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Free Survival ◽  
First Onset ◽  
Clinical Trial Information

5539 Background: In SOLO1 (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit vs placebo in newly diagnosed pts with advanced OC, a BRCAm and clinical complete or partial response to platinum therapy (HR 0.30; 95% CI 0.23–0.41) and was well tolerated (Moore et al. NEJM 2018). We analysed the most common AEs and hematologic AEs in SOLO1. Methods: Pts received olaparib tablets 300 mg twice daily or placebo until progression unless they had no evidence of disease at 2 years, in which case treatment stopped. AEs were graded using CTCAE v4.0. Results: Of 391 pts randomized, 390 (olaparib, 260; placebo, 130) were treated and included in the safety analysis. Median treatment duration was approximately 25 months for olaparib vs 14 for placebo. Median time to first onset of the most common AEs (nausea, vomiting, fatigue/asthenia, anemia) and neutropenia and thrombocytopenia was < 3 months; the first event lasted a median of < 2 months, apart from fatigue/asthenia, which lasted a median of < 4 months (Table). AEs were usually managed with supportive therapy and/or dose modification; few pts discontinued. Conclusions: AEs in newly diagnosed pts with advanced OC treated with olaparib usually occurred early and were manageable, with few discontinuations. Clinical trial information: NCT01844986. [Table: see text]

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

2020 ◽  
Vol 21 (11) ◽  
pp. 3805 ◽  
Author(s):  
Michele Bartoletti ◽  
Giacomo Pelizzari ◽  
Lorenzo Gerratana ◽  
Lucia Bortot ◽  
Davide Lombardi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Parp Inhibitors ◽  
Free Survival ◽  
Significance Level ◽  
Platinum Sensitive ◽  
Brca Genes ◽  
Brca 1

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.

Biologicals in the Upfront Treatment of Ovarian Cancer: Focus on Bevacizumab and Poly (ADP-Ribose) Polymerase Inhibitors

2012 ◽  
pp. 340-344
Author(s):  
Rene Roux ◽  
Martin Zweifel ◽  
Gordon J. S. Rustin
Keyword(s):  
Ovarian Cancer ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Free Survival ◽  
Polymerase Inhibitors ◽  
Hazard Ratios

Overview: Biologicals have made a major impact in the management of several cancers, but have hitherto had a negligible impact in ovarian cancer. Fortunately, ovarian cancer has been much more sensitive to cytotoxic chemotherapy than many cancers, so treatments were still available. However, improvements are required as more than 80% of patients who present with advanced ovarian cancer eventually will die as a result of their disease. The antiangiogenic antibody bevacizumab and the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib have recently been shown to improve progression-free survival of patients with ovarian cancer with better hazard ratios in certain groups than have been seen previously.

scholarly journals Estimating long-term overall survival with olaparib as maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations

2021 ◽  
Vol 17 (3) ◽  
pp. 97-105
Author(s):  
N. A. Avxentyev ◽  
S. V. Khokhlova ◽  
M. Yu. Frolov ◽  
A. S. Makarov
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
First Line ◽  
Brca Mutations ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Line Chemotherapy

Background. According to randomized clinical trial SOLO1 olaparib statistically significantly improves progression-free survival versus placebo as a maintenance monotherapy in patients aged 18 and over with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy. As the data on overall survival (OS) in this trial remains interim it is still uncertain whether treatment with olaparib can provide any benefits in terms of OS.Objective: to evaluate a long-term OS for olaparib versus placebo as a maintenance monotherapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response to first-line chemotherapy.Materials and methods. A 10-year mathematic model of disease progression and survival on olaparib versus placebo was developed. Modelling was based on data on progression-free survival from SOLO1 trial and data on OS after platinum-sensitive and platinum-resistant relapses from OCEANS and AURELIA trials. Additionally, patients who haven’t been treated with olaparib after first-line therapy in base-case scenario were assumed to get olaparib as a second-line treatment after platinum-sensitive relapse; mortality modelling for these patients was based on data from SOLO2 trial.Results. Median OS for olaparib was 107 months versus 66 months for placebo. 46 % of patients treated with olaparib were alive by the end of 10-year modelling period, but only 28 % patients from the placebo group. Hazard ratio of death for olaparib versus placebo was 0.64 (95 % confidence interval 0.49–0.84). Probabilistic sensitivity analysis showed robustness of these results.Conclusion. Using olaparib as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer with BRCA mutations, who had response on first line chemotherapy, statistically significantly reduces risk of death by 36 %, compared to placebo.

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