scholarly journals Feasibility Study of a Network Meta-Analysis and Unanchored Population-Adjusted Indirect Treatment Comparison of Niraparib, Olaparib, and Bevacizumab as Maintenance Therapies in Patients with Newly Diagnosed Advanced Ovarian Cancer

2020 ◽  
Author(s):  
Domenica Lorusso ◽  
Holly Guy ◽  
Jean Hamilton ◽  
Yevgeniy Samyshkin ◽  
Karin Travers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Feasibility Study ◽  
Meta Analysis ◽  
Advanced Ovarian Cancer ◽  
Newly Diagnosed ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Indirect Treatment

scholarly journals Population-adjusted indirect treatment comparison of maintenance PARP inhibitor with or without bevacizumab versus bevacizumab alone in women with newly diagnosed advanced ovarian cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110496
Author(s):  
Robert Hettle ◽  
Charles McCrea ◽  
Chee Khoon Lee ◽  
Richard Davidson
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Treatment ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Newly Diagnosed ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Unselected Population ◽  
Indirect Treatment ◽  
Positive Population

Background: In patients with newly diagnosed ovarian cancer, bevacizumab and poly(ADP-ribose) polymerase (PARP) inhibitors, alone or in combination, have shown benefit as maintenance treatment following platinum-based chemotherapy. However, no trials have compared a PARP inhibitor plus bevacizumab versus a PARP inhibitor, or a PARP inhibitor versus bevacizumab. We performed an unanchored population-adjusted indirect treatment comparison to estimate the relative efficacy and safety of maintenance treatments for newly diagnosed advanced ovarian cancer. Methods: Analyses were performed using aggregate data from the PRIMA trial and patient-level data from a subset of patients from the PAOLA-1 trial that met surgery and staging eligibility criteria of PRIMA. Propensity weights were used to match baseline characteristics of the PAOLA-1 subset to those of the PRIMA population. Analysis was performed in overall (biomarker-unselected) and homologous recombination repair deficiency (HRD)-positive populations. Results: A total of 595/806 (266/387 HRD-positive) PAOLA-1 patients were included. After matching, the effective sample size for PAOLA-1 was 532 (242 HRD-positive). Maintenance olaparib plus bevacizumab reduced the risk of disease progression or death by 43% [hazard ratio (HR) 0.57; 95% confidence interval (CI): 0.47–0.69] versus niraparib and by 40% (HR 0.60; 95% CI: 0.49–0.74) versus bevacizumab in the biomarker-unselected population and by 43% (HR 0.57; 95% CI: 0.41–0.79) and 60% (HR 0.40; 95% CI: 0.29–0.55), respectively, in the HRD-positive population. Progression-free survival (PFS) benefits of maintenance niraparib and bevacizumab arms were comparable in the biomarker-unselected population (HR 1.07; 95% CI: 0.87–1.32); however, niraparib showed a 30% reduced risk compared with bevacizumab (HR 0.70; 95% CI: 0.51–0.97) in the HRD-positive population. Conclusions: In biomarker-unselected and HRD-positive patients, combination treatment with olaparib plus bevacizumab as maintenance treatment improves PFS for women with newly diagnosed advanced ovarian cancer compared with either bevacizumab or niraparib alone. Results are hypothesis generating and could guide randomised trial design.

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.

scholarly journals Causal inference and adjustment for reference-arm risk in indirect treatment comparison meta-analysis

2020 ◽  
Vol 9 (10) ◽  
pp. 737-750
Author(s):  
Elyse Swallow ◽  
Oscar Patterson-Lomba ◽  
Rajeev Ayyagari ◽  
Corey Pelletier ◽  
Rina Mehta ◽  
...  
Keyword(s):  
Causal Inference ◽  
Treatment Effects ◽  
Meta Analysis ◽  
Real Data ◽  
Indirect Treatment Comparison ◽  
Common Reference ◽  
Treatment Comparison ◽  
Improve Model ◽  
Indirect Treatment ◽  
Meta Analyses

Aim: To illustrate that bias associated with indirect treatment comparison and network meta-analyses can be reduced by adjusting for outcomes on common reference arms. Materials & methods: Approaches to adjusting for reference-arm effects are presented within a causal inference framework. Bayesian and Frequentist approaches are applied to three real data examples. Results: Reference-arm adjustment can significantly impact estimated treatment differences, improve model fit and align indirectly estimated treatment effects with those observed in randomized trials. Reference-arm adjustment can possibly reverse the direction of estimated treatment effects. Conclusion: Accumulating theoretical and empirical evidence underscores the importance of adjusting for reference-arm outcomes in indirect treatment comparison and network meta-analyses to make full use of data and reduce the risk of bias in estimated treatments effects.

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